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Sample records for canine distemper vaccine

  1. 9 CFR 113.201 - Canine Distemper Vaccine, Killed Virus.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Canine Distemper Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.201 Canine Distemper Vaccine, Killed Virus. Canine Distemper Vaccine... been established as pure, safe, and immunogenic shall be used for vaccine production. All serials...

  2. 9 CFR 113.201 - Canine Distemper Vaccine, Killed Virus.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Canine Distemper Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.201 Canine Distemper Vaccine, Killed Virus. Canine Distemper Vaccine... been established as pure, safe, and immunogenic shall be used for vaccine production. All serials...

  3. 9 CFR 113.201 - Canine Distemper Vaccine, Killed Virus.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Canine Distemper Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.201 Canine Distemper Vaccine, Killed Virus. Canine Distemper Vaccine... been established as pure, safe, and immunogenic shall be used for vaccine production. All serials...

  4. 9 CFR 113.201 - Canine Distemper Vaccine, Killed Virus.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Canine Distemper Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.201 Canine Distemper Vaccine, Killed Virus. Canine Distemper Vaccine... been established as pure, safe, and immunogenic shall be used for vaccine production. All serials...

  5. 9 CFR 113.201 - Canine Distemper Vaccine, Killed Virus.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Canine Distemper Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.201 Canine Distemper Vaccine, Killed Virus. Canine Distemper Vaccine... been established as pure, safe, and immunogenic shall be used for vaccine production. All serials...

  6. 9 CFR 113.306 - Canine Distemper Vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Canine Distemper Vaccine. 113.306... Virus Vaccines § 113.306 Canine Distemper Vaccine. Canine Distemper Vaccine shall be prepared from virus... as pure, safe, and immunogenic shall be used for preparing the production seed virus for...

  7. 9 CFR 113.306 - Canine Distemper Vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Canine Distemper Vaccine. 113.306... Virus Vaccines § 113.306 Canine Distemper Vaccine. Canine Distemper Vaccine shall be prepared from virus... as pure, safe, and immunogenic shall be used for preparing the production seed virus for...

  8. 9 CFR 113.306 - Canine Distemper Vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Canine Distemper Vaccine. 113.306... Virus Vaccines § 113.306 Canine Distemper Vaccine. Canine Distemper Vaccine shall be prepared from virus... as pure, safe, and immunogenic shall be used for preparing the production seed virus for...

  9. 9 CFR 113.306 - Canine Distemper Vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Canine Distemper Vaccine. 113.306... Virus Vaccines § 113.306 Canine Distemper Vaccine. Canine Distemper Vaccine shall be prepared from virus... as pure, safe, and immunogenic shall be used for preparing the production seed virus for...

  10. 9 CFR 113.306 - Canine Distemper Vaccine.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Canine Distemper Vaccine. 113.306... Virus Vaccines § 113.306 Canine Distemper Vaccine. Canine Distemper Vaccine shall be prepared from virus... as pure, safe, and immunogenic shall be used for preparing the production seed virus for...

  11. Recombinant canine distemper virus serves as bivalent live vaccine against rabies and canine distemper.

    PubMed

    Wang, Xijun; Feng, Na; Ge, Jinying; Shuai, Lei; Peng, Liyan; Gao, Yuwei; Yang, Songtao; Xia, Xianzhu; Bu, Zhigao

    2012-07-20

    Effective, safe, and affordable rabies vaccines are still being sought. Attenuated live vaccine has been widely used to protect carnivores from canine distemper. In this study, we generated a recombinant canine distemper virus (CDV) vaccine strain, rCDV-RVG, expressing the rabies virus glycoprotein (RVG) by using reverse genetics. The recombinant virus rCDV-RVG retained growth properties similar to those of vector CDV in Vero cell culture. Animal studies demonstrated that rCDV-RVG was safe in mice and dogs. Mice inoculated intracerebrally or intramuscularly with rCDV-RVG showed no apparent signs of disease and developed a strong rabies virus (RABV) neutralizing antibody response, which completely protected mice from challenge with a lethal dose of street virus. Canine studies showed that vaccination with rCDV-RVG induced strong and long-lasting virus neutralizing antibody responses to RABV and CDV. This is the first study demonstrating that recombinant CDV has the potential to serve as bivalent live vaccine against rabies and canine distemper in animals.

  12. A comparison of canine distemper vaccine and measles vaccine for the prevention of canine distemper in young puppies.

    PubMed

    Chalmers, W S; Baxendale, W

    1994-10-08

    Two groups of six-week-old beagle puppies were vaccinated with either high titre canine distemper virus or human measles virus, a third group remaining unvaccinated. All the puppies were subsequently challenged by the nasopharyngeal route at 10 weeks old with the virulent Snyder-Hill strain of canine distemper. Severe clinical signs were observed in 90 per cent of the unvaccinated dogs but both groups of vaccinated dogs survived the challenge. High temperatures were recorded in 20 per cent of the measles vaccinates and abdominal petechial rashes were observed in 60 per cent of them. The only clinical signs observed in the puppies vaccinated with distemper virus were transient rashes in 20 per cent of the group. The high titre canine distemper vaccine stimulated a humoral response quickly in 78 per cent of the puppies in the presence of maternally derived antibody and protected them against challenge with the virulent Snyder-Hill strain of distemper virus. The remaining dogs responded sluggishly but were still protected against challenge. The results of field surveys showed that 95 per cent of young puppies with different levels of maternally derived antibodies responded to the distemper component in a vaccine also containing canine parvovirus. No incompatibility was observed between the two components.

  13. Clinical trials with canine distemper vaccines in exotic carnivores.

    PubMed

    Montali, R J; Bartz, C R; Teare, J A; Allen, J T; Appel, M J; Bush, M

    1983-12-01

    Two types of killed canine distemper virus (CDV) vaccine and a modified-live CDV vaccine were clinically evaluated in four species of exotic carnivores. In 16 trials in which 13 red pandas (Ailurus fulgens) were given the killed vaccine, only 1 animal had a virus-neutralization titer that exceeded 1:100. A red panda given modified-live CDV vaccine deemed safe for gray foxes and ferrets died of bacterial pneumonia 16 days later. There was no pathologic evidence of canine distemper in that panda. The same modified-live vaccine proved to be immunogenic and safe in 12 bush dogs (Speothos venaticus), 5 maned wolves (Chrysocyon brachyurus), and 3 fennec foxes (Fennecus zerda) in which virus-neutralization titers often exceeded 1:512 and persisted for several months after vaccination.

  14. Serologic response of maned wolves (Chrysocyon brachyurus) to canine and canine parvovirus vaccination distemper virus.

    PubMed

    Maia, O B; Gouveia, A M

    2001-03-01

    This study evaluated the immune response of 47 (22 males, 25 females) captive maned wolves (Chrysocyon brachyurus) to modified-live canine parvovirus and canine distemper virus (Onderstepoort and Rockborn strains) vaccines. Sera were collected from 33 adults and 14 pups, including five free-ranging pups captured at 1 yr of age or younger. All the adults and four captive-born pups had been vaccinated prior to this first blood collection. Virus neutralization and hemagglutination-inhibition assays were performed for quantitating antibodies against canine distemper and canine parvovirus, respectively. Distemper antibody titers > or = 100 were present in 57% of adults and 14% of pups. All adults and 29% of pups had parvovirus antibody titers > or = 80. After vaccination, 72% of the wolves developed antibody titers > or = 100 against distemper and 98% developed titers > or = 80 against parvovirus. Both vaccines used were safe and immunogenic to juvenile and adult maned wolves, regardless of prior vaccination history.

  15. Comparative analyses of canine distemper viral isolates from clinical cases of canine distemper in vaccinated dogs.

    PubMed

    Lan, N T; Yamaguchi, R; Inomata, A; Furuya, Y; Uchida, K; Sugano, S; Tateyama, S

    2006-06-15

    Sequence and phylogenetic analyses of three isolates of canine distemper virus (CDV) isolated from three dogs with a vaccination history were compared with the same analyses of vaccine virus isolated from a vaccine used for dogs. The three dogs showed clinical signs of a recent major type of CD in Japan, including oculonasal discharge and diarrhea, and pathological findings including non-suppurative encephalitis, pneumonia, mild gastroenteritis and lymphoid depletion. Inclusion bodies were in the stomach without inflammation and encephalitis was without clinical signs. One of the highest titers of CDV in different organs of the three dogs was commonly systemic lymphatic organs, including the spleen, lymph nodes and tonsils. New isolates of CDV joined to the clades of the Asia 1 group that is far from the vaccine group. These results surely indicate that wild strains of CDV from dogs with a vaccination history were not reversed vaccine virus, and that the dogs showed characteristics of recent CD in Japan.

  16. Canine Distemper

    MedlinePlus

    ... and, often, the nervous systems of puppies and dogs. The virus also infects wild canids (e.g. ... How is Canine Distemper virus spread? Puppies and dogs usually become infected through airborne exposure to the ...

  17. Immunogenicity of an inactivated oil-emulsion canine distemper vaccine in African wild dogs.

    PubMed

    Cirone, Francesco; Elia, Gabriella; Campolo, Marco; Friedrich, Klaus; Martella, Vito; Pratelli, Annamaria; Buonavoglia, Canio

    2004-04-01

    The immunogenicity of an inactivated oil-emulsion vaccine against canine distemper virus was evaluated in nine captive African wild dogs (Lycaon pictus). Antibody levels were determined by neutralization test in Vero cells. No significant local or systemic adverse reactions were observed in the animals. Virus neutralizing antibody levels >1:20 were detected, especially in animals that were vaccinated twice. The use of oil adjuvants is suggested as a good way to enhance the immune response to inactivated canine distemper vaccine.

  18. Canine distemper virus.

    PubMed

    Martella, Vito; Elia, Gabrielle; Buonavoglia, Canio

    2008-07-01

    Vaccine-based prophylaxis has greatly helped to keep distemper disease under control. Notwithstanding, the incidence of canine distemper virus (CDV)-related disease in canine populations throughout the world seems to have increased in the past decades, and several episodes of CDV disease in vaccinated animals have been reported, with nation-wide proportions in some cases. Increasing surveillance should be pivotal to identify new CDV variants and to understand the dynamics of CDV epidemiology. In addition, it is important to evaluate whether the efficacy of the vaccine against these new strains may somehow be affected.

  19. Clinical and serological response of wild dogs (Lycaon pictus) to vaccination against canine distemper, canine parvovirus infection and rabies.

    PubMed

    van Heerden, J; Bingham, J; van Vuuren, M; Burroughs, R E J; Stylianides, E

    2002-03-01

    Wild dogs Lycaon pictuis (n = 8) were vaccinated 4 times against canine distemper (n = 8) (initially with inactivated and subsequently with live attenuated strains of canine distemper) and canine parvovirus infection (n = 8) over a period of 360 days. Four of the wild dogs were also vaccinated 3 times against rabies using a live oral vaccine and 4 with an inactivated parenteral vaccine. Commercially-available canine distemper, canine parvovirus and parenteral rabies vaccines, intended for use in domestic dogs, were used. None of the vaccinated dogs showed any untoward clinical signs. The inactivated canine distemper vaccine did not result in seroconversion whereas the attenuated live vaccine resulted in seroconversion in all wild dogs. Presumably protective concentrations of antibodies to canine distemper virus were present in all wild dogs for at least 451 days. Canine parvovirus haemagglutination inhibition titres were present in all wild dogs prior to the administration of vaccine and protective concentrations persisted for at least 451 days. Vaccination against parvovirus infection resulted in a temporary increase in canine parvovirus haemagglutination inhibition titres in most dogs. Administration of both inactivated parenteral and live oral rabies vaccine initially resulted in seroconversion in 7 of 8 dogs. These titres, however, dropped to very low concentrations within 100 days. Booster administrations resulted in increased antibody concentrations in all dogs. It was concluded that the vaccines were safe to use in healthy subadult wild dogs and that a vaccination protocol in free-ranging wild dogs should at least incorporate booster vaccinations against rabies 3-6 months after the first inoculation.

  20. Effect of recombinant canine distemper vaccine on antibody titers in previously vaccinated dogs.

    PubMed

    Larson, L J; Hageny, T L; Haase, C J; Schultz, R D

    2006-01-01

    Two canine distemper virus (CDV) vaccine types are currently commercially available: modified-live virus (MLV) vaccines and a canarypox recombinant CDV (rCDV) vaccine (Recombitek, Merial). This study compared the ability of the rCDV vaccine and MLV vaccines to significantly enhance (boost) the antibody response of previously immunized adult and juvenile dogs. A significant (fourfold or greater) increase in titer occurred in significantly more dogs revaccinated with Recombitek C-4 or Recombitek C-6 than with the MLV-CDV vaccines. This study demonstrates that Recombitek, the only vaccine for dogs containing rCDV, is more likely to significantly boost the CDV antibody response in previously vaccinated dogs than are the MLV-CDV vaccines. Because rCDV vaccine can boost the antibody titer of dogs previously vaccinated with an MLV vaccine, it can and should be used when core vaccines are readministered.

  1. Fatal vaccine-induced canine distemper virus infection in black-footed ferrets

    USGS Publications Warehouse

    Carpenter, J.W.; Appel, M.J.G.; Erickson, R.C.; Novilla, M.N.

    1976-01-01

    Four black-footed ferrets that were live-trapped in South Dakota and transported to the Patuxent Wildlife Research Center died within 21 days after vaccination with modified live canine distemper virus. Immunofluorescence, European ferret inoculation, virus isolation attempts, and serum-neutralization tests indicated insufficient attenuation of the vaccine for this species.

  2. Evaluation of the efficacy and duration of immunity of a canine combination vaccine against virulent parvovirus, infectious canine hepatitis virus, and distemper virus experimental challenges.

    PubMed

    Abdelmagid, Omar Y; Larson, Laurie; Payne, Laurie; Tubbs, Anna; Wasmoen, Terri; Schultz, Ronald

    2004-01-01

    The results of this study confirmed that dogs vaccinated subcutaneously with a commercially available multivalent vaccine containing modified-live canine distemper virus, canine adenovirus type 2, canine parvovirus type 2b, and canine parainfluenza virus antigens were protected against sequential experimental challenge 55 to 57 months after initial vaccination given at 7 to 8 weeks of age. All 10 vaccinates were protected against clinical diseases and mortality following parvovirus and infectious canine hepatitis experimental infections. All vaccinates were protected against mortality and 90% against clinical disease following distemper challenge. These data support at least a 4-year duration of immunity for these three "core" fractions in the combination vaccine.

  3. Canine Distemper Viral Inclusions in Blood Cells of Four Vaccinated Dogs

    PubMed Central

    McLaughlin, Bruce G.; Adams, Pamela S.; Cornell, William D.; Elkins, A. Darrel

    1985-01-01

    Four cases of canine distemper were detected by the presence of numerous cytoplasmic inclusions in various circulating blood cells. Fluorescent antibody techniques and electron microscopy confirmed the identity of the viral inclusions. The cases occurred in the same geographic area and within a short time span. All four dogs had been vaccinated against canine distemper, but stress or other factors may have compromised their immune status. The possibility of an unusually virulent virus strain was also considered. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5. PMID:17422596

  4. Early life DNA vaccination with the H gene of Canine distemper virus induces robust protection against distemper.

    PubMed

    Jensen, Trine Hammer; Nielsen, Line; Aasted, Bent; Blixenkrone-Møller, Merete

    2009-08-20

    Young mink kits (n=8) were vaccinated with DNA plasmids encoding the viral haemagglutinin protein (H) of a vaccine strain of Canine distemper virus (CDV). Virus neutralising (VN) antibodies were induced after 2 immunisations and after the third immunisation all kits had high VN antibody titres. The VN antibody titres remained high for more than 4 months and the mink were protected against viraemia, lymphopenia, clinical disease and changes in the percentage of IFN-gamma producing peripheral blood leucocytes after challenge inoculation with a recent wild type strain of CDV. Essentially, these results demonstrate that early life DNA vaccination with the H gene of a CDV vaccine strain induced robust protective immunity against a recent wild type CDV.

  5. Efficacy of two canine distemper vaccines in wild Nearctic river otters (Lontra canadensis).

    PubMed

    Peper, Steven T; Peper, Randall L; Kollias, George V; Brooks, Robert P; Stevens, Sadie S; Serfass, Thomas L

    2014-09-01

    Canine distemper virus (CDV), a contagious morbillivirus, infects families in the order Carnivora, including Nearctic river otters (Lontra canadensis). As a preventative measure, vaccinations against CDV are frequently given to mustelids in captive environments. The Pennsylvania River Otter Reintroduction Project (PRORP) used wild-caught river otters to evaluate the efficacy and need for vaccinations against CDV as part of any reintroduction project. The objectives of this study were to: 1) evaluate the prevalence of exposure to CDV in wild river otters, 2) determine the immunologic response of river otters (i.e., seroconversion) after vaccination with a single (primary) vaccine dose compared to a second (booster) dose of Galaxy-D, a modified live-virus canine distemper (CD) vaccine (MLV CDV), and 3) determine the immunologic response after being vaccinated with a primary vaccination compared to a booster dose of Fervac-D, an MLV CDV. River otters were injected subcutaneously in the nape of the neck with their designated vaccine. Timeframes for collection of blood samples and/or injection of booster vaccines varied depending on the parameters of PRORP. Ten of the 22 river otters had positive prevaccination titer levels to CD. Both vaccines, Galaxy-D and Fervac-D, produced sufficient seroconversion or rise of titer levels (86% and 57%, respectively) to recommend the use of vaccines in wild river otters. Future studies are recommended to evaluate currently produced CD vaccines. Future research should also focus on the number of days required between administration of primary and booster vaccines to achieve sufficient immune response. If only a primary dose is required, then hard-release reintroduction projects for river otters could be recommended. If primary and booster vaccines are required then soft-release reintroduction projects should be recommended. Soft-release projects should include captive management periods that allow for appropriate vaccination intervals

  6. Duration of immunity in red wolves (Canis rufus) following vaccination with a modified live parvovirus and canine distemper vaccine.

    PubMed

    Anderson, Kadie; Case, Allison; Woodie, Kathleen; Waddell, William; Reed, Holly H

    2014-09-01

    There is growing information available regarding duration of immunity for core vaccines in both domestic and nondomestic species. Vaccination protocols in nondomestic canids have frequently followed guidelines developed for the domestic dog; however, these protocols can be inappropriate for nondomestic canids such as the African wild dog (Lycaon pictus), leaving some animals susceptible to infectious disease and others at risk for contracting vaccine-induced disease. In this study, red wolves (Canis rufus) were vaccinated against canine distemper virus (CDV) and canine parvovirus (CPV) and vaccination titers were followed annually for 3 yr. One hundred percent of wolves developed and maintained a positive titer to CDV for 3 yr and 96.9% of wolves developed and maintained a positive titer to CPV for 3 yr. Seroconversion for canine adenovirus was sporadic. The results of this study support decreasing the frequency of vaccine administration in the red wolf population to a triennial basis.

  7. Three-year duration of immunity in dogs following vaccination against canine adenovirus type-1, canine parvovirus, and canine distemper virus.

    PubMed

    Gore, Thomas C; Lakshmanan, Nallakannu; Duncan, Karen L; Coyne, Michael J; Lum, Melissa A; Sterner, Frank J

    2005-01-01

    A challenge-of-immunity study was conducted to demonstrate immunity in dogs 3 years after their second vaccination with a new multivalent, modified-live vaccine containing canine adenovirus type 2 (CAV-2), canine parvovirus (CPV), and canine distemper virus (CDV). Twenty-three seronegative pups were vaccinated at 7 and 11 weeks of age. Eighteen seronegative pups, randomized into groups of six dogs, served as challenge controls. Dogs were kept in strict isolation for 3 years following the vaccination and then challenged sequentially with virulent canine adenovirus type 1 (CAV-1), CPV, and CDV. For each viral challenge, a separate group of six control dogs was also challenged. Clinical signs of CAV-1, CPV, and CDV infections were prevented in 100% of vaccinated dogs, demonstrating that the multivalent, modified-live test vaccine provided protection against virulent CAV-1, CPV, and CDV challenge in dogs 7 weeks of age or older for a minimum of 3 years following second vaccination.

  8. Vaccine coverage, herd immunity and occurrence of canine distemper from 1990-1996 in Finland.

    PubMed

    Rikula, Ulla; Nuotio, Lasse; Sihvonen, Liisa

    2007-11-19

    Official vaccine sales statistics, the development of the young dog population and the takes of available vaccines were used to calculate the vaccine coverage and herd immunity (HI) against canine distemper, endemic during 1990-1993 and epidemic in 1994-1995 in Finland. Despite the satisfactory vaccine coverage, HI was no more than 50-65% in 1990-1993 because low-take vaccines dominated the market. Replacement of the low-take with high-take vaccines in 1995 raised the HI to 90%, which coincided with the ending of the epidemic. In 1996, the HI was slightly above 70%, which was sufficient to control the disease despite infectious pressure caused by repeated imports.

  9. Comparison of oral and intramuscular recombinant canine distemper vaccination in African wild dogs (Lycaon pictus).

    PubMed

    Connolly, Maren; Thomas, Patrick; Woodroffe, Rosie; Raphael, Bonnie L

    2013-12-01

    A series of three doses of recombinant canary-pox-vectored canine distemper virus vaccine was administered at 1-mo intervals, orally (n = 8) or intramuscularly (n = 13), to 21 previously unvaccinated juvenile African wild dogs (Lycaon pictus) at the Wildlife Conservation Society's Bronx Zoo. Titers were measured by serum neutralization at each vaccination and at intervals over a period of 3.5-21.5 mo after the initial vaccination. All postvaccination titers were negative for orally vaccinated animals at all sampling time points. Of the animals that received intramuscular vaccinations, 100% had presumed protective titers by the end of the course of vaccination, but only 50% of those sampled at 6.5 mo postvaccination had positive titers. None of the three animals sampled at 21.5 mo postvaccination had positive titers.

  10. The quest for a safe and effective canine distemper virus vaccine for black-footed ferrets

    USGS Publications Warehouse

    Wimsatt, Jeffrey; Biggins, Dean E.; Williams, Elizabeth S.; Becerra, Victor M.

    2006-01-01

    Canine distemper virus (CDV) causes a systemic disease that is highly virulent to mustelids and other carnivore (Order Carnivora) species and is found worldwide. Endemic canine distemper in wild and domestic carnivores in the United States has made reintroduction of endangered black-footed ferrets (Mustela nigripes) difficult in the absence of safe and effective CDV vaccines and vaccination practices. Toward this end, researchers have explored appropriate animal models and vaccine preparations in highly susceptible species. Published studies involving domestic ferrets (M. putorius furo) using Galaxy-D® and evaluating a recombinant canarypox-vectored vaccine for oral administration are reviewed. In addition, we present new findings in domestic and black-footed ferrets and Siberian polecats (M. eversmannii) that have extended our understanding of CDV in the black-footed ferret and other at-risk carnivore species. Original research presented here includes trials that determined an effective challenge dose (by route) of virulent CDV in domestic ferrets and Siberian polecats; the low likelihood of collateral vaccination with Galaxy-D; the adverse effect of modified-live virus boostering in black-footed ferrets receiving killed vaccine previously and the response of Siberian polecats receiving canarypoxvectored recombinant CDV vaccine (reCDV); the absence of an effect of reCDV vaccination on conception, pregnancy, and neonatal growth in Siberian polecats; and the apparent inefficacy of active reCDV vaccination during the period of passive immunity in young Siberian polecats. In the final section, we discuss emerging concerns and avenues for disease intervention that may present new opportunities to solve problems in vaccine safety, vaccine availability, field vaccine delivery, and other therapeutic modalities.

  11. Cetacean-reconstituted severe combined immunodeficient (SCID) mice respond to vaccination with canine distemper vaccine.

    PubMed

    De Guise, Sylvain; Levin, Milton Jay

    2004-02-01

    Morbillivirus infections have been responsible for mass mortalities in several species of marine mammals. Nevertheless, relatively little is known on the pathogenesis of the disease and the immune response to the agent, especially in cetaceans, hindering the treatment of individuals and the development of appropriate vaccines, given the difficulty of performing experimental work in marine mammals. The reconstitution of severe combined immunodeficient (SCID) mice, which do not have the ability to reject grafts, with lymphocytes from different species has been used with increasing success as a surrogate species model to study the immune system. We injected NOD/SCID mice with lymphocytes from different species of cetaceans and further vaccinated those mice with a commercial canine distemper virus (CDV) vaccine to develop a practical model to study cetacean immune response to a morbillivirus. Reconstitution was detected in 10/20 mice reconstituted with harbor porpoise spleen, 6/10 mice reconstituted with harbor porpoise lymph node cells, 8/10 mice reconstituted with fresh beluga PBMCs and none of the mice reconstituted with neonate bottlenose dolphin spleen or thymus cells when assessed 42-63 days after reconstitution. While a humoral immune response was detected in none of the reconstituted mice, a cell-mediated immune response to the CDV vaccine was detected in 6/15 (40%) and 2/18 (11%) of the SCID mice after reconstitution with cetacean immune cells after a single or booster vaccination, respectively, for a combined total of 8/33 (24%). This represents the first demonstration of successful reconstitution of SCID mice with marine mammal cells, and to the authors' knowledge, the first direct demonstration of a primary antigen-specific cell-mediated immune response in reconstituted SCID mice. This model will be useful for further research on the physiology of the marine mammal immune system and its response to infectious agents and vaccines, with possible important

  12. Lights and shades on an historical vaccine canine distemper virus, the Rockborn strain.

    PubMed

    Martella, V; Blixenkrone-Møller, M; Elia, G; Lucente, M S; Cirone, F; Decaro, N; Nielsen, L; Bányai, K; Carmichael, L E; Buonavoglia, C

    2011-02-01

    Both egg- and cell-adapted canine distemper virus (CDV) vaccines are suspected to retain residual virulence, especially if administered to immuno-suppressed animals, very young pups or to highly susceptible animal species. In the early 1980s, post-vaccine encephalitis was reported in dogs from various parts of Britain after administration of a particular batch of combined CDV Rockborn strain/canine adenovirus type-1 vaccine, although incrimination of the Rockborn strain was subsequently retracted. Notwithstanding, this, and other reports, led to the view that the Rockborn strain is less attenuated and less safe than other CDV vaccines, and the Rockborn strain was officially withdrawn from the markets in the mid 1990s. By sequencing the H gene of the strain Rockborn from the 46th laboratory passage, and a commercial vaccine (Candur(®) SH+P, Hoechst Rousell Vet GmbH), the virus was found to differ from the commonly used vaccine strain, Onderstepoort (93.0% nt and 91.7% aa), and to resemble more closely (99.6% nt and 99.3% aa) a CDV strain detected in China from a Lesser Panda (Ailurus fulgens). An additional four CDV strains matching (>99% nt identity) the Rockborn virus were identified in the sequence databases. Also, Rockborn-like strains were identified in two vaccines currently in the market. These findings indicate that Rockborn-like viruses may be recovered from dogs or other carnivores with distemper, suggesting cases of residual virulence of vaccines, or circulation of vaccine-derived Rockborn-like viruses in the field.

  13. Three-year duration of immunity in dogs vaccinated with a canarypox-vectored recombinant canine distemper virus vaccine.

    PubMed

    Larson, L J; Schultz, R D

    2007-01-01

    Two studies evaluated the duration of serologic response to the recombinant, canarypox-vectored canine distemper virus vaccine (Recombitek, Merial). Serologic duration of immunity was shown to be at least 36 months. Thus, Recombitek provides protection when administered less frequently than the manufacturer's label. After the initial vaccination protocol of two or more doses administered approximately 4 weeks apart, with the last dose given at 12 to 16 weeks of age or older, and re-vaccination at 1 year of age, Recombitek can confidently be readministered every 3 years with assurance of protection in immunocompetent dogs. This allows the vaccine to be administered in accordance with the recommendations of the American Animal Hospital Association Canine Vaccine Task Force and others.

  14. Apoptosis in canine distemper.

    PubMed

    Moro, L; de Sousa Martins, A; de Moraes Alves, C; de Araújo Santos, F G; dos Santos Nunes, J E; Carneiro, R A; Carvalho, R; Vasconcelos, A C

    2003-01-01

    Canine distemper is a systemic viral disease characterized by immunosuppression followed by secondary infections. Apoptosis is observed in several immunosuppressive diseases and its occurrence on canine distemper in vivo has not been published. In this study, the occurrence of apoptosis was determined in lymphoid tissues of thirteen naturally infected dogs and nine experimentally inoculated puppies. Healthy dogs were used as negative controls. Samples of lymph nodes, thymus, spleen and brain were collected for histopathological purposes. Sections, 5 microm thick, of retropharingeal lymph nodes were stained by HE, Shorr, Methyl Green-Pyronin and TUNEL reaction. Shorr stained sections were further evaluated by morphometry. Canine distemper virus nucleoprotein was detected by immunohistochemistry. Retropharingeal lymph nodes of naturally and experimentally infected dogs had more apoptotic cells per field than controls. In addition, DNA from thymus of infected dogs were more fragmented than controls. Therefore, apoptosis is increased in lymphoid depletion induced by canine distemper virus and consequently play a role in the immunosuppression seen in this disease.

  15. Canine distemper virus DNA vaccination of mink can overcome interference by maternal antibodies.

    PubMed

    Jensen, Trine Hammer; Nielsen, Line; Aasted, Bent; Pertoldi, Cino; Blixenkrone-Møller, Merete

    2015-03-10

    Canine distemper virus (CDV) is highly contagious and can cause severe disease against which conventional live vaccines are ineffective in the presence of maternal antibodies. Vaccination in the presences of maternal antibodies was challenged by vaccination of 5 days old and 3 weeks old mink kits with CDV DNA vaccines. Virus neutralising (VN) antibody responses were induced in mink kits vaccinated with a plasmid encoding the haemaglutinin protein (H) of CDV (n=5, pCDV-H) or a combination of the H, fusion (F) and nucleoprotein (N) of CDV (n=5, pCDV-HFN). These DNA vaccinated kits were protected against virulent experimental infection with field strains of CDV. The pCDV-H was more efficient in inducing protective immunity in the presence of maternal antibodies compared to the pCDV-HFN. The results show that DNA vaccination with the pCDV-H or pCDV-HFN (n=4) only given once at 5 days of age induces virus specific immune response in neonatal mink and protection against virulent CDV exposure later in life.

  16. CANINE DISTEMPER VIRUS ANTIBODY TITERS IN DOMESTIC CATS AFTER DELIVERY OF A LIVE ATTENUATED VIRUS VACCINE.

    PubMed

    Ramsay, Edward; Sadler, Ryan; Rush, Robert; Seimon, Tracie; Tomaszewicz, Ania; Fleetwood, Ellen A; McAloose, Denise; Wilkes, Rebecca P

    2016-06-01

    Three methods for delivering a live attenuated canine distemper virus (CDV) vaccine to domestic cats ( Felis catus ) were investigated, as models for developing vaccination protocols for tigers (Panthera tigris). Twenty domestic cats were randomly divided into four treatment groups: saline injection (negative controls); and oral, intranasal, and subcutaneous vaccinates. Cats were injected with saline or a CDV vaccine (Nobivac DP, Merck) at wk 0 and 4. Blood and nasal swabs were collected at wk 0 (prior to the initial vaccination) and weekly thereafter for 9 wk. Urine samples were collected on wk 1 to 9 after initial vaccination. Forty-nine weeks following the initial vaccination series, three cats from the subcutaneous group and three cats from the intranasal group were revaccinated. Blood was collected immediately prior, and 7 and 21 days subsequent to revaccination. Nasal swabs and urine samples were collected from each cat prior to wk 49 revaccination and daily for 7 days thereafter. Nasal swabs and urine were analyzed by quantitative PCR for vaccine virus presence. Sera were tested for CDV antibodies by virus neutralization. All cats were sero-negative for CDV antibodies at the beginning of the study, and saline-injected cats remained sero-negative throughout the study. A dramatic anamnestic response was seen following wk 4 subcutaneous vaccinations, with titers peaking at wk 6 (geometric mean = 2,435.5). Following wk 49 revaccination, subcutaneous vaccinates again mounted impressive titers (wk 52 geometric mean = 2,048). Revaccination of the intranasal group cats at wk 49 produced a small increase in titers (wk 52 geometric mean = 203). CDV viral RNA was detected in six nasal swabs but no urine samples, demonstrating low viral shedding postvaccination. The strong antibody response to subcutaneous vaccination and the lack of adverse effects suggest this vaccine is safe and potentially protective against CDV infection in domestic cats.

  17. Controversial results of the genetic analysis of a canine distemper vaccine strain.

    PubMed

    Demeter, Zoltán; Palade, Elena Alina; Hornyák, Akos; Rusvai, Miklós

    2010-05-19

    Canine distemper (CD) is a highly contagious, often fatal, multisystemic viral disease of receptive carnivores. The presence of a PsiI cleavage site on a specific location of the hemagglutinin (H) gene was found to be a hallmark of vaccine strains, thus, a previously published restriction fragment length polymorphism (RFLP) test using PsiI theoretically allows the distinction between all currently used vaccine strains and virulent field strains. The RFLP test was carried out on all brands of CD vaccines available in Hungary. The present work describes the extensive sequencing and phylogenetic study of the strain present in Vanguard (Pfizer Animal Health) vaccines, which following the PsiI based RFLP test reacted as a wild-type strain. Based on the product description provided by the manufacturer, all batches should have contained a virus strain (Snyder Hill) belonging to the group of vaccine strains (America-1). Extensive genetic analysis involving the full nucleic acid sequence of four other genes (N, M, P and F) of the CDV genome revealed that the incriminated virus strain showed a higher level of genetic identity to wild-type strains from the America-2 group than to any of the strains belonging to America-1 group, therefore the vaccine does not contain the virus strain stated by the manufacturer in its product description and has not been containing it since at least 1992.

  18. Measles Vaccination of Nonhuman Primates Provides Partial Protection against Infection with Canine Distemper Virus

    PubMed Central

    de Vries, Rory D.; Ludlow, Martin; Verburgh, R. Joyce; van Amerongen, Geert; Yüksel, Selma; Nguyen, D. Tien; McQuaid, Stephen; Osterhaus, Albert D. M. E.; Duprex, W. Paul

    2014-01-01

    ABSTRACT Measles virus (MV) is being considered for global eradication, which would likely reduce compliance with MV vaccination. As a result, children will grow up without MV-specific immunity, creating a potential niche for closely related animal morbilliviruses such as canine distemper virus (CDV). Natural CDV infection causing clinical signs has never been reported in humans, but recent outbreaks in captive macaques have shown that CDV can cause disease in primates. We studied the virulence and tropism of recombinant CDV expressing enhanced green fluorescent protein in naive and measles-vaccinated cynomolgus macaques. In naive animals CDV caused viremia and fever and predominantly infected CD150+ lymphocytes and dendritic cells. Virus was reisolated from the upper and lower respiratory tracts, but infection of epithelial or neuronal cells was not detectable at the time points examined, and the infections were self-limiting. This demonstrates that CDV readily infects nonhuman primates but suggests that additional mutations are necessary to achieve full virulence in nonnatural hosts. Partial protection against CDV was observed in measles-vaccinated macaques, as demonstrated by accelerated control of virus replication and limited shedding from the upper respiratory tract. While neither CDV infection nor MV vaccination induced detectable cross-reactive neutralizing antibodies, MV-specific neutralizing antibody levels of MV-vaccinated macaques were boosted by CDV challenge infection, suggesting that cross-reactive VN epitopes exist. Rapid increases in white blood cell counts in MV-vaccinated macaques following CDV challenge suggested that cross-reactive cellular immune responses were also present. This study demonstrates that zoonotic morbillivirus infections can be controlled by measles vaccination. IMPORTANCE Throughout history viral zoonoses have had a substantial impact on human health. Given the drive toward global eradication of measles, it is essential to

  19. EVALUATION OF TWO CANINE DISTEMPER VIRUS VACCINES IN CAPTIVE TIGERS (PANTHERA TIGRIS).

    PubMed

    Sadler, Ryan A; Ramsay, Edward; McAloose, Denise; Rush, Robert; Wilkes, Rebecca P

    2016-06-01

    Canine distemper virus (CDV) has caused clinical disease and death in nondomestic felids in both captive settings and in the wild. Outbreaks resulting in high mortality rates in tigers (Panthera tigris) have prompted some zoos to vaccinate tigers for CDV. In this study, six tigers received a recombinant canarypox-vectored CDV vaccine (1 ml s.c.) and were revaccinated with 3 ml s.c. (mean) 39 days later. Blood collection for CDV antibody detection via serum neutralization was performed on (mean) days 0, 26, and 66 post-initial vaccination. No tigers had detectable antibodies at days 0 or 26, and only two tigers had low (16 and 32) antibody titers at day 66. Eight additional tigers received a live, attenuated CDV vaccine (1 ml s.c.) on day 0 and were revaccinated with 1 ml s.c. (mean) 171 days later. Blood collection for CDV antibody detection via serum neutralization was performed on (mean) days 0, 26, 171, and 196. Seven of eight tigers receiving the live, attenuated vaccine had no detectable titers prior to vaccination, but all animals had titers of >128 (range 128-1,024) at day 26. At 171 days, all tigers still had detectable titers (geometric mean 69.8, range 16-256), and at 196 days (2 wk post-revaccination) all but two showed an increase to >128 (range 32-512). To determine safety, an additional 41 tigers were vaccinated with 2 ml of a recombinant vaccine containing only CDV components, and an additional 38 tigers received 1 ml of the live, attenuated vaccine, administered either subcutaneously or intramuscularly; no serious adverse effects were noted. Although both vaccines appear safe, the live, attenuated vaccine produced a stronger and more consistent serologic response in tigers.

  20. Effect of vaccination with recombinant canine distemper virus vaccine immediately before exposure under shelter-like conditions.

    PubMed

    Larson, L J; Schultz, R D

    2006-01-01

    Vaccination with modified-live virus (MLV) canine distemper virus (CDV) vaccine has historically been recommended for animals in high-risk environments because of the rapid onset of immunity following vaccination. Recombinant CDV (rCDV) vaccine was deemed a suitable alternative to MLV-CDV vaccination in pet dogs, but insufficient data precluded its use where CDV was a serious threat to puppies, such as in shelters, kennels, and pet stores. In this study, dogs experimentally challenged hours after a single dose of rCDV or MLV vaccine became sick but recovered, whereas unvaccinated dogs became sick and died. Dogs vaccinated with a single dose of rCDV or MLV vaccine 1 week before being experimentally challenged remained healthy and showed no clinical signs. Dogs given one dose of rCDV vaccine hours before being placed in a CDV-contaminated environment did not become sick. These findings support the hypothesis that rCDV vaccine has a similar time-to-immunity as MLV-CDV vaccines and can likewise protect dogs in high-risk environments after one dose.

  1. Booster effect of canine distemper, canine parvovirus infection and infectious canine hepatitis combination vaccine in domesticated adult dogs.

    PubMed

    Taguchi, Masayuki; Namikawa, Kazuhiko; Maruo, Takuya; Orito, Kensuke; Lynch, Jonathan; Tsuchiya, Ryo; Sahara, Hiroeki

    2012-08-01

    Domesticated adult dogs with antibody titer classified as below 'high' to one or more of canine distemper virus (CDV), canine parvovirus type-2 (CPV-2) and canine adenovirus type-1 (CAdV-1) were then given an additional inoculation, and the effectiveness of this booster evaluated 2 months later. Consequently, CDV and CAdV-1 antibody titer experienced a significant increase, but the same effect was not observed in the antibody titer of CPV-2. These findings suggest that with additional inoculation, a booster effect may be expected in increasing antibody titers for CDV and CAdV-1, but it is unlikely to give an increase in CPV-2 antibody titer.

  2. Comparative trial of the canine parvovirus, canine distemper virus and canine adenovirus type 2 fractions of two commercially available modified live vaccines.

    PubMed

    Bergman, J G H E; Muniz, M; Sutton, D; Fensome, R; Ling, F; Paul, G

    2006-11-25

    The results of vaccinating two groups of puppies with commercial vaccines, both of which claimed to provide adequate protection with a final vaccination at 10 weeks of age, were compared. Groups of 19 and 20 puppies with similar titres of maternally derived antibodies against canine parvovirus (cpv), canine distemper virus (cdv) and canine adenovirus type 2 (cav-2) at four weeks of age were vaccinated at six and 10 weeks of age and their responses to each vaccination were measured by comparing the titres against cpv, cdv and cav-2 in the serum samples taken immediately before the vaccination and four weeks later. After the vaccination at six weeks of age, all 19 of the puppies in group 1 had responded to cpv and cdv, and 14 had responded to cav-2; in group 2, 17 of the 20 had responded to cpv, 19 to cdv and 15 to cav-2. In both groups the puppies that did not respond to the first vaccination had responded serologically to cpv, cdv and cav-2 at 10 weeks of age.

  3. 'Saving the lives of our dogs': the development of canine distemper vaccine in interwar Britain.

    PubMed

    Bresalier, Michael; Worboys, Michael

    2014-06-01

    This paper examines the successful campaign in Britain to develop canine distemper vaccine between 1922 and 1933. The campaign mobilized disparate groups around the common cause of using modern science to save the nation's dogs from a deadly disease. Spearheaded by landed patricians associated with the country journal The Field, and funded by dog owners and associations, it relied on collaborations with veterinary professionals, government scientists, the Medical Research Council (MRC) and the commercial pharmaceutical house the Burroughs Wellcome Company (BWC). The social organization of the campaign reveals a number of important, yet previously unexplored, features of interwar science and medicine in Britain. It depended on a patronage system that drew upon a large base of influential benefactors and public subscriptions. Coordinated by the Field Distemper Fund, this system was characterized by close relationships between landed elites and their social networks with senior science administrators and researchers. Relations between experts and non-experts were crucial, with high levels of public engagement in all aspects of research and vaccine development. At the same time, experimental and commercial research supported under the campaign saw dynamic interactions between animal and human medicine, which shaped the organization of the MRC's research programme and demonstrated the value of close collaboration between veterinary and medical science, with the dog as a shared object and resource. Finally, the campaign made possible the translation of 'laboratory' findings into field conditions and commercial products. Rather than a unidirectional process, translation involved negotiations over the very boundaries of the 'laboratory' and the 'field', and what constituted a viable vaccine. This paper suggests that historians reconsider standard historical accounts of the nature of patronage, the role of animals, and the interests of landed elites in interwar British

  4. Canine distemper vaccination is a safe and useful preventive procedure for southern sea otters (Enhydra lutra nereis).

    PubMed

    Jessup, David A; Murray, Michael J; Casper, David R; Brownstein, Deborah; Kreuder-Johnson, Christine

    2009-12-01

    From 2002 to 2006, eight captive southern sea otters (Enhydra lutris nereis) at research and display institutions in California at risk of exposure to potentially lethal morbiliviruses were vaccinated with a commercial recombinant poxvirus vectored canine distemper (CD) vaccine. Serum-neutralizing (SN) antibody responses were followed for several years. The goal of this study was to determine whether 1) CD vaccination was a safe preventive medicine procedure for this species; 2) sea otters produce detectable SN antibodies in response to vaccination with this product; and 3) if this type of vaccination might be useful in response to a morbilivirus disease outbreak in free-ranging sea otters. Results indicate that a commercial recombinant vaccine is safe, provokes a measurable SN antibody response, and that vaccination may provide some protection from infection for free-ranging sea otters. It also resulted in the reevaluation of CD serology data that were previously published for free-ranging sea otters. Canine distemper, Enhydra lutris nereis, morbilivirus, sea otter, serology, vaccination.

  5. Identification of a genetic variant of canine distemper virus from clinical cases in two vaccinated dogs in Mexico.

    PubMed

    Simon-Martínez, J; Ulloa-Arvizu, R; Soriano, V E; Fajardo, R

    2008-03-01

    Canine distemper virus (CDV) is a highly contagious viral pathogen of worldwide distribution that can cause lethal disease in dogs and other mammals. Genetic diversity is found among reference strains and isolates of CDV, mainly in the haemagglutinin protein (H), fusion protein (F) and nucleoprotein (N), and this may be associated with the increasing incidence of distemper in dogs. CDV was identified by RT-PCR in serum samples taken from two clinically diseased, previously vaccinated Mexican dogs. Subsequently, in both samples, a fragment of the CDV N gene was sequenced revealing a 100% identity between nucleotide sequences. However, the sequence obtained was different to that found in virus strains used in vaccines and in isolates reported elsewhere, but was closely related to A75/17, 1127/Gi95, and 2495/Gi95 sequences from USA and Germany, and clustered with 1127/Gi95 and 2495/Gi95 strains. The results suggest that a novel CDV lineage may be present in Mexico.

  6. Canine distemper outbreak in rhesus monkeys, China.

    PubMed

    Qiu, Wei; Zheng, Ying; Zhang, Shoufeng; Fan, Quanshui; Liu, Hua; Zhang, Fuqiang; Wang, Wei; Liao, Guoyang; Hu, Rongliang

    2011-08-01

    Since 2006, canine distemper outbreaks have occurred in rhesus monkeys at a breeding farm in Guangxi, People's Republic of China. Approximately 10,000 animals were infected (25%-60% disease incidence); 5%-30% of infected animals died. The epidemic was controlled by vaccination. Amino acid sequence analysis of the virus indicated a unique strain.

  7. Seroprevalence of Canine Distemper Virus in Cats

    PubMed Central

    Ikeda, Yasuhiro; Nakamura, Kazuya; Miyazawa, Takayuki; Chen, Ming-Chu; Kuo, Tzong-Fu; Lin, James A.; Mikami, Takeshi; Kai, Chieko; Takahashi, Eiji

    2001-01-01

    A seroepidemiological survey of canine distemper virus (CDV) infection in Asian felids revealed that the prevalence of antibodies varied depending on region and, in some cases, exposure to dogs. The serologic pattern in cats with antibodies indicated that they had likely been exposed to field strains rather than typical CDV vaccine strains. PMID:11329473

  8. Effects of body weight on antibody titers against canine parvovirus type 2, canine distemper virus, and canine adenovirus type 1 in vaccinated domestic adult dogs.

    PubMed

    Taguchi, Masayuki; Namikawa, Kazuhiko; Maruo, Takuya; Saito, Miyoko; Lynch, Jonathan; Sahara, Hiroeki

    2012-10-01

    The objective of this study was to determine whether post-vaccination antibody titers vary according to body weight in adult dogs. Antibody titers against canine parvovirus type 2 (CPV-2), canine distemper virus (CDV), and canine adenovirus type 1 (CAdV-1) were measured for 978 domestic adult dogs from 2 to 6 y of age. The dogs had been vaccinated approximately 12 mo earlier with a commercial combination vaccine. The dogs were divided into groups according to their weight. It was found that mean antibody titers in all weight groups were sufficient to prevent infection. Intergroup comparison, however, revealed that CPV-2 antibody titers were significantly higher in the Super Light (< 5 kg) group than in the Medium (10 to 19.9 kg) and Heavy (> 20 kg) groups and were also significantly higher in the Light (5 to 9.9 kg) group than in the Heavy group. Antibody titers against CDV were significantly higher in the Super Light, Light, and Medium groups than in the Heavy group. There were no significant differences among the groups for the CAdV-1 antibody titers.

  9. Establishment of reverse transcription loop-mediated isothermal amplification for rapid detection and differentiation of canine distemper virus infected and vaccinated animals.

    PubMed

    Liu, Da-Fei; Liu, Chun-Guo; Tian, Jin; Jiang, Yi-Tong; Zhang, Xiao-Zhan; Chai, Hong-Liang; Yang, Tian-Kuo; Yin, Xiu-Chen; Zhang, Hong-Ying; Liu, Ming; Hua, Yu-Ping; Qu, Lian-Dong

    2015-06-01

    Although widespread vaccination against canine distemper virus (CDV) has been conducted for many decades, several canine distemper outbreaks in vaccinated animals have been reported frequently. In order to detect and differentiate the wild-type and vaccine strains of the CDV from the vaccinated animals, a novel reverse transcription loop-mediated isothermal amplification (RT-LAMP) method was developed. A set of four primers-two internal and two external-were designed to target the H gene for the specific detection of wild-type CDV variants. The CDV-H RT-LAMP assay rapidly amplified the target gene, within 60 min, using a water bath held at a constant temperature of 65°C. The assay was 100-fold more sensitive than conventional RT-PCR, with a detection limit of 10(-1)TCID50ml(-1). The system showed a preference for wild-type CDV, and exhibited less sensitivity to canine parvovirus, canine adenovirus type 1 and type 2, canine coronavirus, and canine parainfluenza virus. The assay was validated using 102 clinical samples obtained from vaccinated dog farms, and the results were comparable to a multiplex nested RT-PCR assay. The specific CDV-H RT-LAMP assay provides a simple, rapid, and sensitive tool for the detection of canines infected with wild-type CDV from canines vaccinated with attenuated vaccine.

  10. Serologic responses after vaccination of fennec foxes (Vulpes zerda) and meerkats (Suricata suricatta) with a live, canarypox-vectored canine distemper virus vaccine.

    PubMed

    Coke, Rob L; Backues, Kay A; Hoover, John P; Saliki, Jeremiah T; Ritchey, Jerry W; West, Gary D

    2005-06-01

    Fennec foxes (Vulpes zerda) and meerkats (Suricata suricatta) are considered to be susceptible to canine distemper virus (CDV) infection. Although no definitive clinical cases of natural CDV infections have been reported, mortalities due to CDV have been suspected and are reported in other closely related species. A commercially available monovalent, live, canarypox-vectored CDV vaccine induced neutralizing antibody titers that were maintained for at least a year in both fennec foxes and meerkats.

  11. Evaluation of oral and subcutaneous delivery of an experimental canarypox recombinant canine distemper vaccine in the Siberian polecate (Mustela eversmanni)

    USGS Publications Warehouse

    Wimsatt, Jeffrey; Biggins, Dean E.; Innes, Kim; Taylor, Bobbi; Garell, Della

    2003-01-01

    We assessed the safety and efficacy of an experimental canarypox-vectored recombinant canine distemper virus (CDV) subunit vaccine in the Siberian polecat (Mustela eversmanni), a close relative of the black-footed ferret, (M. nigripes), an endangered species that is highly susceptible to the virus. Siberian polecats were randomized into six treatment groups. Recombinant canine distemper vaccine was administered s.c. at three dose levels (104.5, 105.0, and 105.5 plaque-forming units [PFU] per dose) and was administered orally by spraying the vaccine into the oropharnyx at two dose levels (105.5, 108.0 PFU per dose). The sixth group of control animals was not vaccinated. For both routes of administration, two 1-ml doses of reconstituted vaccine were delivered 4 wk apart, followed by live virus challenge 3 wk after the second vaccination. During the challenge, Synder Hill test strain CDV obtained from the National Veterinary Services Laboratory in Ames, Iowa, was administered i.p. Serial blood samples for CDV serology were collected immediately before vaccination and challenge, and 10, 15, and 20 days after challenge. Clinical signs and body weights were recorded up to 32 days after challenge. The survival rate in animals receiving vaccine at the highest oral dose (108.0 PFU per dose) was 83.3%. Survival rate was 50.0% in the high s.c. and 60.0% in the medium s.c. groups. All animals in the low–s.c. dose, low–oral dose, and control groups died after exposure. Vaccine dose overall (oral and s.c.) and dose in response to s.c. administration when considered alone were significant predictors of survival (P = 0.006 and P = 0.04, respectively). Among the polecats challenged with virulent virus, those that died became sick sooner than those that survived. Animals that died lost significantly more weight during the 10 days after challenge than did animals that survived (P = 0.02). Survival rates did not differ by sex, founder female status, or breeding pedigree in any of

  12. Canine distemper virus (CDV) infection of ferrets as a model for testing Morbillivirus vaccine strategies: NYVAC- and ALVAC-based CDV recombinants protect against symptomatic infection.

    PubMed Central

    Stephensen, C B; Welter, J; Thaker, S R; Taylor, J; Tartaglia, J; Paoletti, E

    1997-01-01

    Canine distemper virus (CDV) infection of ferrets causes an acute systemic disease involving multiple organ systems, including the respiratory tract, lymphoid system, and central nervous system (CNS). We have tested candidate CDV vaccines incorporating the fusion (F) and hemagglutinin (HA) proteins in the highly attenuated NYVAC strain of vaccinia virus and in the ALVAC strain of canarypox virus, which does not productively replicate in mammalian hosts. Juvenile ferrets were vaccinated twice with these constructs, or with an attenuated live-virus vaccine, while controls received saline or the NYVAC and ALVAC vectors expressing rabies virus glycoprotein. Control animals did not develop neutralizing antibody and succumbed to distemper after developing fever, weight loss, leukocytopenia, decreased activity, conjunctivitis, an erythematous rash typical of distemper, CNS signs, and viremia in peripheral blood mononuclear cells (as measured by reverse transcription-PCR). All three CDV vaccines elicited neutralizing titers of at least 1:96. All vaccinated ferrets survived, and none developed viremia. Both recombinant vaccines also protected against the development of symptomatic distemper. However, ferrets receiving the live-virus vaccine lost weight, became lymphocytopenic, and developed the erythematous rash typical of CDV. These data show that ferrets are an excellent model for evaluating the ability of CDV vaccines to protect against symptomatic infection. Because the pathogenesis and clinical course of CDV infection of ferrets is quite similar to that of other Morbillivirus infections, including measles, this model will be useful in testing new candidate Morbillivirus vaccines. PMID:8995676

  13. Canine distemper virus (CDV) infection of ferrets as a model for testing Morbillivirus vaccine strategies: NYVAC- and ALVAC-based CDV recombinants protect against symptomatic infection.

    PubMed

    Stephensen, C B; Welter, J; Thaker, S R; Taylor, J; Tartaglia, J; Paoletti, E

    1997-02-01

    Canine distemper virus (CDV) infection of ferrets causes an acute systemic disease involving multiple organ systems, including the respiratory tract, lymphoid system, and central nervous system (CNS). We have tested candidate CDV vaccines incorporating the fusion (F) and hemagglutinin (HA) proteins in the highly attenuated NYVAC strain of vaccinia virus and in the ALVAC strain of canarypox virus, which does not productively replicate in mammalian hosts. Juvenile ferrets were vaccinated twice with these constructs, or with an attenuated live-virus vaccine, while controls received saline or the NYVAC and ALVAC vectors expressing rabies virus glycoprotein. Control animals did not develop neutralizing antibody and succumbed to distemper after developing fever, weight loss, leukocytopenia, decreased activity, conjunctivitis, an erythematous rash typical of distemper, CNS signs, and viremia in peripheral blood mononuclear cells (as measured by reverse transcription-PCR). All three CDV vaccines elicited neutralizing titers of at least 1:96. All vaccinated ferrets survived, and none developed viremia. Both recombinant vaccines also protected against the development of symptomatic distemper. However, ferrets receiving the live-virus vaccine lost weight, became lymphocytopenic, and developed the erythematous rash typical of CDV. These data show that ferrets are an excellent model for evaluating the ability of CDV vaccines to protect against symptomatic infection. Because the pathogenesis and clinical course of CDV infection of ferrets is quite similar to that of other Morbillivirus infections, including measles, this model will be useful in testing new candidate Morbillivirus vaccines.

  14. Three-year rabies duration of immunity in dogs following vaccination with a core combination vaccine against canine distemper virus, canine adenovirus type-1, canine parvovirus, and rabies virus.

    PubMed

    Lakshmanan, Nallakannu; Gore, Thomas C; Duncan, Karen L; Coyne, Michael J; Lum, Melissa A; Sterner, Frank J

    2006-01-01

    Thirty-two seronegative pups were vaccinated at 8 weeks of age with modified-live canine distemper virus (CDV), canine adenovirus type-2 (CAV-2), and canine parvovirus (CPV) vaccine and at 12 weeks with a modified-live CDV, CAV-2, CPV, and killed rabies virus vaccine. An additional 31 seronegative pups served as age-matched, nonvaccinated controls. All test dogs were strictly isolated for 3 years after receiving the second vaccination and then were challenged with virulent rabies virus. Clinical signs of rabies were prevented in 28 (88%) of the 32 vaccinated dogs. In contrast, 97% (30 of 31) of the control dogs died of rabies infection. These study results indicated that no immunogenic interference occurred between the modified-live vaccine components and the killed rabies virus component. Furthermore, these results indicated that the rabies component in the test vaccine provided protection against virulent rabies challenge in dogs 12 weeks of age or older for a minimum of 3 years following vaccination.

  15. Vaccination against canine distemper virus infection in infant ferrets with and without maternal antibody protection, using recombinant attenuated poxvirus vaccines.

    PubMed

    Welter, J; Taylor, J; Tartaglia, J; Paoletti, E; Stephensen, C B

    2000-07-01

    Canine distemper virus (CDV) infection of ferrets is clinically and immunologically similar to measles, making this a useful model for the human disease. The model was used to determine if parenteral or mucosal immunization of infant ferrets at 3 and 6 weeks of age with attenuated vaccinia virus (NYVAC) or canarypox virus (ALVAC) vaccine strains expressing the CDV hemagglutinin (H) and fusion (F) protein genes (NYVAC-HF and ALVAC-HF) would induce serum neutralizing antibody and protect against challenge infection at 12 weeks of age. Ferrets without maternal antibody that were vaccinated parenterally with NYVAC-HF (n = 5) or ALVAC-HF (n = 4) developed significant neutralizing titers (log(10) inverse mean titer +/- standard deviation of 2.30 +/- 0.12 and 2.20 +/- 0.34, respectively) by the day of challenge, and all survived with no clinical or virologic evidence of infection. Ferrets without maternal antibody that were vaccinated intranasally (i.n.) developed lower neutralizing titers, with NYVAC-HF producing higher titers at challenge (1.11 +/- 0.57 versus 0.40 +/- 0.37, P = 0.02) and a better survival rate (6/7 versus 0/5, P = 0.008) than ALVAC-HF. Ferrets with maternal antibody that were vaccinated parenterally with NYVAC-HF (n = 7) and ALVAC-HF (n = 7) developed significantly higher antibody titers (1.64 +/- 0. 54 and 1.28 +/- 0.40, respectively) than did ferrets immunized with an attenuated CDV vaccine (0.46 +/- 0.59; n = 7) or the recombinant vectors expressing rabies glycoprotein (RG) (0.19 +/- 0.32; n = 8, P = 7 x 10(-6)). The NYVAC vaccine also protected against weight loss, and both the NYVAC and attenuated CDV vaccines protected against the development of some clinical signs of infection, although survival in each of the three vaccine groups was low (one of seven) and not significantly different from the RG controls (none of eight). Combined i.n.-parenteral immunization of ferrets with maternal antibody using NYVAC-HF (n = 9) produced higher titers (1

  16. Comparative efficacy of a canine distemper-measles and a standard measles vaccine for immunization of rhesus macaques (Macaca mulatta).

    PubMed

    Christe, Kari L; McChesney, Michael B; Spinner, Abigail; Rosenthal, Ann N; Allen, Philip C; Valverde, Celia R; Roberts, Jeffrey A; Lerche, Nicholas W

    2002-10-01

    Measles virus (MV), a highly infective paramyxovirus, has caused sporadic epizootics characterized by high morbidity and increased mortality in nonhuman primates. Measles vaccines for human use, although effective, are cost prohibitive for use in primate colonies. We compared the efficacy of one or two doses of Vanguard D-M, a canine distemper-measles (CD-M) vaccine, with a single dose of Attenuvax, a human measles vaccine. Compared with 81% of animals inoculated with Attenuvax, all animals inoculated with one or two doses of Vanguard developed detectable MV antibodies. One year after immunization, six juveniles from each vaccine group, along with three unvaccinated controls, were challenged with pathogenic MV and were monitored for clinical signs of disease, viremia, viral shedding, and immune response. All uninoculated controls developed clinical disease and viremia, and shed virus in nasopharangeal secretions. Subclinical viremia without viral shedding was identified in two Attenuvax- and two single-dose Vanguard-inoculated animals. Viremia was not detected in any two-dose Vanguard-inoculated animals. Significantly higher neutralization antibody titers were observed in animals receiving Vanguard. Results of this study indicate that Vanguard is at least as efficacious as Attenuvax for protection of rhesus macaques. The considerably lower cost of Vanguard makes vaccination against measles in large breeding colonies economically feasible.

  17. Analysis of the H gene, the central untranslated region and the proximal coding part of the F gene of wild-type and vaccine canine distemper viruses.

    PubMed

    Haas, L; Liermann, H; Harder, T C; Barrett, T; Löchelt, M; von Messling, V; Baumgärtner, W; Greiser-Wilke, I

    1999-09-01

    This paper summarizes the results of the genetic analysis of several parts of the genome of canine distemper virus (CDV) field isolates and vaccine viruses. The haemagglutinin (H) gene analysis showed that recent viruses did not differ significantly from vaccine strains. The analysis of the long untranslated region between the matrix (M) and fusion (F) gene revealed distinct genetic heterogeneity. The putative F protein start codon AUG461 of vaccine strain Onderstepoort was found to be mutated in all wild-type isolates and in another vaccine strain. The proximal coding part of the F gene was well conserved. Phylogenetic analysis of this segment showed the presence of several cocirculating CDV genotypes.

  18. Detection and differentiation of wild-type and vaccine strains of canine distemper virus by a duplex reverse transcription polymerase chain reaction

    PubMed Central

    Dong, X. Y.; Li, W. H.; Zhu, J. L.; Liu, W. J.; Zhao, M. Q.; Luo, Y. W.; Chen, J. D.

    2015-01-01

    Canine distemper virus (CDV) is the cause of canine distemper (CD) which is a severe and highly contagious disease in dogs. In the present study, a duplex reverse transcription polymerase chain reaction (RT-PCR) method was developed for the detection and differentiation of wild-type and vaccine strains of CDV. Four primers were designed to detect and discriminate the two viruses by generating 638- and 781-bp cDNA products, respectively. Furthermore, the duplex RT-PCR method was used to detect 67 field samples suspected of CD from Guangdong province in China. Results showed that, 33 samples were to be wild-type-like. The duplex RT-PCR method exhibited high specificity and sensitivity which could be used to effectively detect and differentiate wild-type and vaccine CDV, indicating its use for clinical detection and epidemiological surveillance. PMID:27175171

  19. Use of serologic tests to predict resistance to Canine distemper virus-induced disease in vaccinated dogs.

    PubMed

    Jensen, Wayne A; Totten, Janet S; Lappin, Michael R; Schultz, Ronald D

    2015-09-01

    The objective of the current study was to determine whether detection of Canine distemper virus (CDV)-specific serum antibodies correlates with resistance to challenge with virulent virus. Virus neutralization (VN) assay results were compared with resistance to viral challenge in 2 unvaccinated Beagle puppies, 9 unvaccinated Beagle dogs (4.4-7.2 years of age), and 9 vaccinated Beagle dogs (3.7-4.7 years of age). Eight of 9 (89%) unvaccinated adult dogs exhibited clinical signs after virus challenge, and 1 (13%) dog died. As compared to adult dogs, the 2 unvaccinated puppies developed more severe clinical signs and either died or were euthanized after challenge. In contrast, no clinical signs were detected after challenge of the 9 adult vaccinated dogs with post-vaccination intervals of up to 4.4 years. In vaccinated dogs, the positive and negative predictive values of VN assay results for resistance to challenge were 100% and 0%, respectively. Results indicate that dogs vaccinated with modified live CDV can be protected from challenge for ≤4.4 years postvaccination and that detection of virus-specific antibodies is predictive of whether dogs are resistant to challenge with virulent virus. Results also indicate that CDV infection in unvaccinated dogs results in age-dependent morbidity and mortality. Knowledge of age-dependent morbidity and mortality, duration of vaccine-induced immunity, and the positive and negative predictive values of detection of virus-specific serum antibodies are useful in development of rational booster vaccination intervals for the prevention of CDV-mediated disease in adult dogs.

  20. Canine distemper virus DNA vaccination induces humoral and cellular immunity and protects against a lethal intracerebral challenge.

    PubMed

    Sixt, N; Cardoso, A; Vallier, A; Fayolle, J; Buckland, R; Wild, T F

    1998-11-01

    We have studied the immune responses to the two glycoproteins of the Morbillivirus canine distemper virus (CDV) after DNA vaccination of BALB/c mice. The plasmids coding for both CDV hemagglutinin (H) and fusion protein (F) induce high levels of antibodies which persist for more than 6 months. Intramuscular inoculation of the CDV DNA induces a predominantly immunoglobulin G2a (IgG2a) response (Th1 response), whereas gene gun immunization with CDV H evokes exclusively an IgG1 response (Th2 response). In contrast, the CDV F gene elicited a mixed, IgG1 and IgG2a response. Mice vaccinated (by gene gun) with either the CDV H or F DNA showed a class I-restricted cytotoxic lymphocyte response. Immunized mice challenged intracerebrally with a lethal dose of a neurovirulent strain of CDV were protected. However, approximately 30% of the mice vaccinated with the CDV F DNA became obese in the first 2 months following the challenge. This was not correlated with the serum antibody levels.

  1. Adjuvant effects of recombinant giant panda (Ailuropoda melanoleuca) IL-18 on the canine distemper disease vaccine in mice.

    PubMed

    Yan, Yue; Niu, Lili; Deng, Jiabo; Wang, Qiang; Yu, Jianqiu; Zhang, Yizheng; Wang, Jianxi; Chen, Jiao; Wei, Changhe; Tan, Xuemei

    2015-02-01

    Canine distemper virus (CDV) is a morbillivirus known to cause morbidity and mortality in a broad range of animals. Giant pandas (Ailuropoda melanoleuca), especially captive ones, are susceptible to natural infection with CDV. Interleukin-18 (IL-18) is a powerful adjuvant molecule that can enhance the development of antigen-specific immunity and vaccine efficacy. In this study, a giant panda IL-18 gene eukaryotic expression plasmid (pcAmIL-18) was constructed. Female BALB/c mice were muscularly inoculated with the plasmids pcAmIL-18, pcDNA3.1 and PBS, respectively. They were subsequently injected with an attenuated CDV vaccine for dogs, and the induced humoral and cellular responses were evaluated. The results showed that pcAmIL-18 remarkably improved the level of specific antibody, IFN-γ and IL-2 in mice sera, the T lymphocyte proliferation index and the percentage of CD4(+) and CD8(+) cells. These data indicated that pcAmIL-18 is a potential adjuvant that promotes specific immunity.

  2. Adjuvant effects of recombinant giant panda (Ailuropoda melanoleuca) IL-18 on the canine distemper disease vaccine in mice

    PubMed Central

    YAN, Yue; NIU, Lili; DENG, Jiabo; WANG, Qiang; YU, Jianqiu; ZHANG, Yizheng; WANG, Jianxi; CHEN, Jiao; WEI, Changhe; TAN, Xuemei

    2014-01-01

    Canine distemper virus (CDV) is a morbillivirus known to cause morbidity and mortality in a broad range of animals. Giant pandas (Ailuropoda melanoleuca), especially captive ones, are susceptible to natural infection with CDV. Interleukin-18 (IL-18) is a powerful adjuvant molecule that can enhance the development of antigen-specific immunity and vaccine efficacy. In this study, a giant panda IL-18 gene eukaryotic expression plasmid (pcAmIL-18) was constructed. Female BALB/c mice were muscularly inoculated with the plasmids pcAmIL-18, pcDNA3.1 and PBS, respectively. They were subsequently injected with an attenuated CDV vaccine for dogs, and the induced humoral and cellular responses were evaluated. The results showed that pcAmIL-18 remarkably improved the level of specific antibody, IFN-γ and IL-2 in mice sera, the T lymphocyte proliferation index and the percentage of CD4+ and CD8+ cells. These data indicated that pcAmIL-18 is a potential adjuvant that promotes specific immunity. PMID:25399820

  3. A multiplex reverse transcription-nested polymerase chain reaction for detection and differentiation of wild-type and vaccine strains of canine distemper virus.

    PubMed

    Si, Wei; Zhou, Shun; Wang, Zhao; Cui, Shang-jin

    2010-05-01

    A multiplex reverse transcription-nested polymerase chain reaction (RT-nPCR) method was developed for the detection and differentiation of wild-type and vaccine strains of canine distemper virus (CDV). A pair of primers (P1 and P4) specific for CDV corresponding to the highly conserved region of the CDV genome were used as a common primer pair in the first-round PCR of the nested PCR. Primers P2 specific for CDV wild-type strains, were used as the forward primer together with the common reverse primer P4 in the second round of nested PCR. Primers P3, P5 specific for CDV wild-type strain or vaccine strain, were used as the forward primer together with the common reverse primer P4+P6 in the second round of nested PCR. A fragment of 177 bp was amplified from vaccine strain genomic RNA, and a fragment of 247 bp from wild-type strain genomic RNA in the RT-nPCR, and two fragments of 247 bp and 177 bp were amplified from the mixed samples of vaccine and wild-type strains. No amplification was achieved for uninfected cells, or cells infected with Newcastle disease virus (NDV), canine parvovirus (CPV), canine coronavirus (CCV), rabies virus (RV), or canine adenovirus (CAV). The RT-nPCR method was used to detect 30 field samples suspected of canine distemper from Heilongjiang and Jilin Provinces, and 51 samples in Shandong province. As a result of 30 samples, were found to be wild-type-like, and 5 to be vaccine-strain-like. The RT-nPCR method can be used to effectively detect and differentiate wild-type CDV-infected dogs from dogs vaccinated with CDV vaccine, and thus can be used in clinical detection and epidemiological surveillance.

  4. Display of neutralizing epitopes of Canine parvovirus and a T-cell epitope of the fusion protein of Canine distemper virus on chimeric tymovirus-like particles and its use as a vaccine candidate both against Canine parvo and Canine distemper.

    PubMed

    Chandran, Dev; Shahana, Pallichera Vijayan; Rani, Gudavelli Sudha; Sugumar, Parthasarthy; Shankar, Chinchkar Ramchandra; Srinivasan, Villuppanoor Alwar

    2009-12-10

    Expression of Physalis mottle tymovirus coat protein in Escherichia coli was earlier shown to self-assemble into empty capsids that were nearly identical to the capsids formed in vivo. Amino acid substitutions were made at the N-terminus of wild-type Physalis mottle virus coat protein with neutralizing epitopes of Canine parvovirus containing the antigenic sites 1-2, 4 and 6-7 and T-cell epitope of the fusion protein of Canine distemper virus in various combinations to yield PhMV1, PhMV2, PhMV3, PhMV4 and PhMV5. These constructs were cloned and expressed in E. coli. The chimeric proteins self-assembled into chimeric tymovirus-like particles (TVLPs) as determined by electron microscopy. The TVLPs were purified by ultracentrifugation and injected into guinea pigs and dogs to determine their immunogenicity. Initial immunogenicity studies in guinea pigs indicated that PhMV3 gave a higher response in comparison to the other TVLPs for both CPV and CDV and hence all further experiments in dogs were done with PhMV3. HI was done against different isolates obtained from various parts of the country. Protective titres indicated the broad spectrum of the vaccine. In conclusion the study indicated that the above chimeric VLP based vaccine could be used in dogs to generate a protective immune response against diseases caused by both Canine parvo and Canine distemper virus.

  5. Detection and differentiation of field and vaccine strains of canine distemper virus using reverse transcription followed by nested real time PCR (RT-nqPCR) and RFLP analysis.

    PubMed

    Fischer, Cristine Dossin Bastos; Ikuta, Nilo; Canal, Cláudio Wageck; Makiejczuk, Aline; Allgayer, Mariangela da Costa; Cardoso, Cristine Hoffmeister; Lehmann, Fernanda Kieling; Fonseca, André Salvador Kazantzi; Lunge, Vagner Ricardo

    2013-12-01

    Canine distemper virus (CDV) is the cause of a severe and highly contagious disease in dogs. Practical diagnosis of canine distemper based on clinical signs and laboratory tests are required to confirm CDV infection. The present study aimed to develop a molecular assay to detect and differentiate field and vaccine CDV strains. Reverse transcription followed by nested real time polymerase chain reaction (RT-nqPCR) was developed, which exhibited analytical specificity (all the samples from healthy dogs and other canine infectious agents were not incorrectly detected) and sensitivity (all replicates of a vaccine strain were positive up to the 3125-fold dilution - 10(0.7) TCID50). RT-nqPCR was validated for CDV detection on different clinical samples (blood, urine, rectal and conjunctival swabs) of 103 animals suspected to have distemper. A total of 53 animals were found to be positive based on RT-nqPCR in at least one clinical sample. Blood resulted in more positive samples (50 out of 53, 94.3%), followed by urine (44/53, 83.0%), rectal (38/53, 71%) and conjunctival (27/53, 50.9%) swabs. A commercial immunochromatography (IC) assay had detected CDV in only 30 conjunctival samples of these positive dogs. Nucleoprotein (NC) gene sequencing of 25 samples demonstrated that 23 of them were closer to other Brazilian field strains and the remaining two to vaccine strains. A single nucleotide sequences difference, which creates an Msp I restriction enzyme digestion, was used to differentiate between field and vaccine CDV strains by restriction fragment length polymorphism (RFLP) analysis. The complete assay was more sensitive than was IC for the detection of CDV. Blood was the more frequently positive specimen and the addition of a restriction enzyme step allowed the differentiation of vaccine and Brazilian field strains.

  6. Canine distemper spillover in domestic dogs from urban wildlife.

    PubMed

    Kapil, Sanjay; Yeary, Teresa J

    2011-11-01

    Canine distemper virus (CDV) causes a major disease of domestic dogs that develops as a serious systemic infection in unvaccinated or improperly vaccinated dogs. Domesticated dogs are the main reservoir of CDV, a multihost pathogen. This virus of the genus Morbillivirus in the family Paramyxoviridae occurs in other carnivorous species including all members of the Canidae and Mustelidae families and in some members of the Procyonidae, Hyaenidae, Ursidae, and Viverridae families. Canine distemper also has been reported in the Felidae family and marine mammals. The spread and incidences of CDV epidemics in dogs and wildlife here and worldwide are increasing.

  7. Immunopathogenic and Neurological Mechanisms of Canine Distemper Virus

    PubMed Central

    Carvalho, Otávio Valério; Botelho, Clarisse Vieira; Ferreira, Caroline Gracielle Torres; Scherer, Paulo Oldemar; Soares-Martins, Jamária Adriana Pinheiro; Almeida, Márcia Rogéria; Silva Júnior, Abelardo

    2012-01-01

    Canine distemper is a highly contagious viral disease caused by the canine distemper virus (CDV), which is a member of the Morbillivirus genus, Paramyxoviridae family. Animals that most commonly suffer from this disease belong to the Canidae family; however, the spectrum of natural hosts for CDV also includes several other families of the order Carnivora. The infectious disease presents worldwide distribution and maintains a high incidence and high levels of lethality, despite the availability of effective vaccines, and no specific treatment. CDV infection in dogs is characterized by the presentation of systemic and/or neurological courses, and viral persistence in some organs, including the central nervous system (CNS) and lymphoid tissues. An elucidation of the pathogenic mechanisms involved in canine distemper disease will lead to a better understanding of the injuries and clinical manifestations caused by CDV. Ultimately, further insight about this disease will enable the improvement of diagnostic methods as well as therapeutic studies. PMID:23193403

  8. A comparison of the immune responses of dogs exposed to canine distemper virus (CDV) - Differences between vaccinated and wild-type virus exposed dogs.

    PubMed

    Perrone, Danielle; Bender, Scott; Niewiesk, Stefan

    2010-07-01

    Canine distemper virus (CDV)-specific immune response was measured in different dog populations. Three groups of vaccinated or wild-type virus exposed dogs were tested: dogs with a known vaccination history, dogs without a known vaccination history (shelter dogs), and dogs with potential exposure to wild-type CDV. The use of a T-cell proliferation assay demonstrated a detectable CDV-specific T-cell response from both spleen and blood lymphocytes of dogs. Qualitatively, antibody assays [enzyme-linked immunosorbent assay (ELISA) and neutralization assay] predicted the presence of a T-cell response well, although quantitatively neither antibody assays nor the T-cell assay correlated well with each other. An interesting finding from our study was that half of the dogs in shelters were not vaccinated (potentially posing a public veterinary health problem) and that antibody levels in dogs living in an environment with endemic CDV were lower than in vaccinated animals.

  9. Serum antibody titres to canine parvovirus, adenovirus and distemper virus in dogs in the UK which had not been vaccinated for at least three years.

    PubMed

    Böhm, M; Thompson, H; Weir, A; Hasted, A M; Maxwell, N S; Herrtage, M E

    2004-04-10

    Antibody titres to canine distemper (CDV), canine parvovirus (CPV) and canine adenovirus (CAV) were measured in 144 adult dogs that had not been vaccinated for between three and 15 years. Protective antibodies to CPV were present in 95 per cent of the population, to CDV in 71.5 per cent and to CAV in 82 per cent. The prevalence of protective titres did not decrease with increasing time interval from the last vaccination for any of the three diseases studied. Booster vaccination increased the dogs CAV titres. For comparative purposes, 199 puppies were sampled at the time of their first and second vaccination. In the case of CPV and CAV a significantly higher proportion of the adult dogs were protected than of the puppies immediately after they were vaccinated. Natural CPV boosting was strongly suspected because the dogs had significantly higher titres three years after their primary vaccination than two weeks after it and three unvaccinated dogs had acquired protective antibody levels uneventfully. There was no evidence of natural exposure to CDV.

  10. Membrane-bound SIV envelope trimers are immunogenic in ferrets after intranasal vaccination with a replication-competent canine distemper virus vector.

    PubMed

    Zhang, Xinsheng; Wallace, Olivia; Wright, Kevin J; Backer, Martin; Coleman, John W; Koehnke, Rebecca; Frenk, Esther; Domi, Arban; Chiuchiolo, Maria J; DeStefano, Joanne; Narpala, Sandeep; Powell, Rebecca; Morrow, Gavin; Boggiano, Cesar; Zamb, Timothy J; Richter King, C; Parks, Christopher L

    2013-11-01

    We are investigating canine distemper virus (CDV) as a vaccine vector for the delivery of HIV envelope (Env) that closely resembles the native trimeric spike. We selected CDV because it will promote vaccine delivery to lymphoid tissues, and because human exposure is infrequent, reducing potential effects of pre-existing immunity. Using SIV Env as a model, we tested a number of vector and gene insert designs. Vectors containing a gene inserted between the CDV H and L genes, which encoded Env lacking most of its cytoplasmic tail, propagated efficiently in Vero cells, expressed the immunogen on the cell surface, and incorporated the SIV glycoprotein into progeny virus particles. When ferrets were vaccinated intranasally, there were no signs of distress, vector replication was observed in the gut-associated lymphoid tissues, and the animals produced anti-SIV Env antibodies. These data show that live CDV-SIV Env vectors can safely induce anti-Env immune responses following intranasal vaccination.

  11. Phylogenetic evidence of canine distemper virus in Serengeti's lions.

    PubMed

    Harder, T C; Kenter, M; Appel, M J; Roelke-Parker, M E; Barrett, T; Osterhaus, A D

    1995-04-01

    Recently an epizootic, reported to be due to a morbillivirus infection, affected the lion population of the Tanzanian Serengeti National Park. A morbillivirus phosphoprotein (P) gene fragment was amplified by PCR from tissue samples of several affected lions. Sequencing of the amplificates and subsequent phylogenetic analyses revealed that a wild-type strain of canine distemper morbillivirus (CDV) was involved. Vaccination of the local domestic dog population with proven safe CDV vaccines is proposed.

  12. Severe canine distemper outbreak in unvaccinated dogs in Mozambique.

    PubMed

    Zacarias, Julieta; Dimande, Alberto; Achá, Sara; Dias, Paula T; Leonel, Elisa M; Messa, Aurora; Macucule, Baltazar; Júnior, José L; Bila, Custódio G

    2016-07-15

    Although significant animal suffering caused by preventable diseases is frequently seen in developing countries, reports of this are scarce. This report describes avoidable animal suffering owing to a suspected canine distemper (CD) outbreak in unvaccinated dogs owned by low-income families in Mozambique that killed approximately 200 animals. Affected dogs exhibited clinical signs, and gross and microscopic lesions compatible with CD. Immunohistochemical staining confirmed the presence of canine distemper virus (CDV) in the kidney of one dog from the cohort. This brief communication again illustrates that large outbreaks of CDV in unvaccinated dogs occur and that large-scale avoidable suffering and threats to the health of dogs and wild canines continue. Mass vaccination supported by government and non-government organisations is recommended.

  13. Emergence of canine distemper virus strains with two amino acid substitutions in the haemagglutinin protein, detected from vaccinated carnivores in North-Eastern China in 2012-2013.

    PubMed

    Zhao, Jianjun; Zhang, Hailing; Bai, Xue; Martella, Vito; Hu, Bo; Sun, Yangang; Zhu, Chunsheng; Zhang, Lei; Liu, Hao; Xu, Shujuan; Shao, Xiqun; Wu, Wei; Yan, Xijun

    2014-04-01

    A total of 16 strains of canine distemper virus (CDV) were detected from vaccinated minks, foxes, and raccoon dogs in four provinces in North-Eastern China between the end of 2011 and 2013. Upon sequence analysis of the haemagglutinin gene and comparison with wild-type CDV from different species in the same geographical areas, two non-synonymous single nucleotide polymorphisms were identified in 10 CDV strains, which led to amino acid changes at positions 542 (isoleucine to asparagine) and 549 (tyrosine to histidine) of the haemagglutinin protein coding sequence. The change at residue 542 generated a potentially novel N-glycosylation site. Masking of antigenic epitopes by sugar moieties might represent a mechanism for evasion of virus neutralising antibodies and reduced protection by vaccination.

  14. The humoral immune response to recombinant nucleocapsid antigen of canine distemper virus in dogs vaccinated with attenuated distemper virus or DNA encoding the nucleocapsid of wild-type virus.

    PubMed

    Griot-Wenk, M E; Cherpillod, P; Koch, A; Zurbriggen, R; Bruckner, L; Wittek, R; Zurbriggen, A

    2001-06-01

    This study compared the humoral immune response against the nucleocapsid-(N) protein of canine distemper virus (CDV) of dogs vaccinated with a multivalent vaccine against parvo-, adeno-, and parainfluenza virus and leptospira combined with either the attenuated CDV Onderstepoort strain (n = 15) or an expression plasmid containing the N-gene of CDV (n = 30). The vaccinations were applied intramuscularly three times at 2-week intervals beginning at the age of 6 weeks. None of the pre-immune sera recognized the recombinant N-protein, confirming the lack of maternal antibodies at this age. Immunization with DNA vaccine for CDV resulted in positive serum N-specific IgG response. However, their IgG (and IgA) titres were lower than those of CDV-vaccinated dogs. Likewise, DNA-vaccinated dogs did not show an IgM peak. There was no increase in N-specific serum IgE titres in either group. Serum titres to the other multivalent vaccine components were similar in both groups.

  15. DNA vaccines encoding proteins from wild-type and attenuated canine distemper virus protect equally well against wild-type virus challenge.

    PubMed

    Nielsen, Line; Jensen, Trine Hammer; Kristensen, Birte; Jensen, Tove Dannemann; Karlskov-Mortensen, Peter; Lund, Morten; Aasted, Bent; Blixenkrone-Møller, Merete

    2012-10-01

    Immunity induced by DNA vaccines containing the hemagglutinin (H) and nucleoprotein (N) genes of wild-type and attenuated canine distemper virus (CDV) was investigated in mink (Mustela vison), a highly susceptible natural host of CDV. All DNA-immunized mink seroconverted, and significant levels of virus-neutralizing (VN) antibodies were present on the day of challenge with wild-type CDV. The DNA vaccines also primed the cell-mediated memory responses, as indicated by an early increase in the number of interferon-gamma (IFN-γ)-producing lymphocytes after challenge. Importantly, the wild-type and attenuated CDV DNA vaccines had a long-term protective effect against wild-type CDV challenge. The vaccine-induced immunity induced by the H and N genes from wild-type CDV and those from attenuated CDV was comparable. Because these two DNA vaccines were shown to protect equally well against wild-type virus challenge, it is suggested that the genetic/antigenic heterogeneity between vaccine strains and contemporary wild-type strains are unlikely to cause vaccine failure.

  16. Characterization of two recent Japanese field isolates of canine distemper virus and examination of the avirulent strain utility as an attenuated vaccine.

    PubMed

    Takenaka, Akiko; Yoneda, Misako; Seki, Takahiro; Uema, Masashi; Kooriyama, Takanori; Nishi, Toshiya; Fujita, Kentaro; Miura, Ryuichi; Tsukiyama-Kohara, Kyoko; Sato, Hiroki; Kai, Chieko

    2014-12-05

    Recently, several new strains of canine distemper virus (CDV) have been isolated in Japan. To investigate their pathogenesis in dogs, the Yanaka and Bunkyo-K strains were investigated by infecting dogs and determining clinical signs, amount of virus, and antibody responses. The Yanaka strain is avirulent and induced an antibody response. The Bunkyo-K strain induced typical CDV clinical signs in infected dogs and virulence was enhanced by brain passage. Molecular and phylogenetic analyses of H genes demonstrated the Bunkyo-K strains were of a different lineage from Asia-1 group including the Yanaka strain and Asia-2 group that contain recent Japanese isolates, which were recently identified as major prevalent strains worldwide but distinct from old vaccine strains. Based on these data, we tested the ability of the Yanaka strain for vaccination. Inoculation with the Yanaka strain efficiently induced CDV neutralizing antibodies with no clinical signs, and the protection effects against challenge with either old virulent strain or Bunkyo-K strain were equal or greater when compared with vaccination by an original vaccine strain. Thus, the Yanaka strain is a potential vaccine candidate against recent prevalent CDV strains.

  17. A canine distemper outbreak in Alaska: diagnosis and strain characterization using sequence analysis.

    PubMed

    Maes, Roger K; Wise, Annabel G; Fitzgerald, Scott D; Ramudo, Albert; Kline, Joseph; Vilnis, Aivars; Benson, Cherie

    2003-05-01

    Vaccination with modified-live vaccines has been very effective in reducing the incidence of canine distemper, a disease that can be devastating in unvaccinated populations. A diagnostic submission to the Animal Health Diagnostic Laboratory at Michigan State University, East Lansing, Michigan, involved a case in which several hundred dogs in an Alaskan town died in a suspected canine distemper outbreak. Cytoplasmic and intranuclear eosinophilic inclusion bodies, consistent with canine distemper virus (CDV) infection, were found in urinary bladder, spleen, lung, and salivary gland. Direct fluorescent antibody test gave results that could be considered positive for canine distemper. Because of the condition of the tissues received, the histopathology and fluorescent antibody-staining results were suggestive but not conclusive of CDV. In this study, immunohistochemistry, reverse transcriptase-polymerase chain reaction (RT-PCR), and DNA sequencing were used to confirm the presence of canine distemper virus in these tissues and to perform molecular characterization of the virus. Immunohistochemistry showed the presence of the virus in spleen, lung, and salivary gland. Viral RNA was detected by RT-PCR in brain, spleen, liver, lung, and kidney, both with nucleoprotein and phosphoprotein (P)-gene-specific primers. Sequence alignment and phylogenetic analysis of a 540-bp P-gene fragment of the Alaskan strain with corresponding sequences of 2 vaccine and 7 wild-type CDV strains showed that the virus responsible for the outbreak was closely related to a virulent strain of distemper virus from Siberia.

  18. Canine distemper virus antigen detection in external epithelia of recently vaccinated, sick dogs by fluorescence microscopy is a valuable prognostic indicator.

    PubMed

    Kapil, Sanjay; Neel, Tina

    2015-02-01

    Currently, there are no reliable predictors of the clinical outcomes of domesticated dogs that have been recently vaccinated against canine distemper virus (CDV) and develop respiratory disease. In this study, vaccinated dogs from Oklahoma City that were showing clinical signs of respiratory disease were evaluated for CDV antigen using a direct fluorescent antibody test (FAT). Clinical outcomes after standard symptomatic therapy for respiratory disease were recorded, and a statistical analysis of the results was performed. We present our study showing that CDV FAT results were predictive of clinical recovery (prognostic indicator, prospects of clinical recovery) among vaccinated dogs showing clinical signs of respiratory disease. Negative CDV FAT results equated to 80% chances of recovery after symptomatic therapy, compared to 55% chances of recovery when the CDV FAT results were positive. Based on the results of this study, we show that veterinarians can make better informed decisions about the clinical outcomes of suspected CDV cases, with 2-h turnaround times, by using the CDV FAT. Thus, antemortem examination with the CDV FAT on external epithelia of recently vaccinated, sick dogs is a clinically useful diagnostic test and valuable prognostic indicator for veterinarians. Application of the CDV FAT to these samples avoids unnecessary euthanasia of dogs with suspected CDV.

  19. Real-time reverse transcription polymerase chain reaction method for detection of Canine distemper virus modified live vaccine shedding for differentiation from infection with wild-type strains.

    PubMed

    Wilkes, Rebecca P; Sanchez, Elena; Riley, Matthew C; Kennedy, Melissa A

    2014-01-01

    Canine distemper virus (CDV) remains a common cause of infectious disease in dogs, particularly in high-density housing situations such as shelters. Vaccination of all dogs against CDV is recommended at the time of admission to animal shelters and many use a modified live virus (MLV) vaccine. From a diagnostic standpoint for dogs with suspected CDV infection, this is problematic because highly sensitive diagnostic real-time reverse transcription polymerase chain reaction (RT-PCR) tests are able to detect MLV virus in clinical samples. Real-time PCR can be used to quantitate amount of virus shedding and can differentiate vaccine strains from wild-type strains when shedding is high. However, differentiation by quantitation is not possible in vaccinated animals during acute infection, when shedding is low and could be mistaken for low level vaccine virus shedding. While there are gel-based RT-PCR assays for differentiation of vaccine strains from field strains based on sequence differences, the sensitivity of these assays is unable to match that of the real-time RT-PCR assay currently used in the authors' laboratory. Therefore, a real-time RT-PCR assay was developed that detects CDV MLV vaccine strains and distinguishes them from wild-type strains based on nucleotide sequence differences, rather than the amount of viral RNA in the sample. The test is highly sensitive, with detection of as few as 5 virus genomic copies (corresponding to 10(-1) TCID(50)). Sequencing of the DNA real-time products also allows phylogenetic differentiation of the wild-type strains. This test will aid diagnosis during outbreaks of CDV in recently vaccinated animals.

  20. Development of a challenge-protective vaccine concept by modification of the viral RNA-dependent RNA polymerase of canine distemper virus.

    PubMed

    Silin, D; Lyubomska, O; Ludlow, M; Duprex, W P; Rima, B K

    2007-12-01

    We demonstrate that insertion of the open reading frame of enhanced green fluorescent protein (EGFP) into the coding sequence for the second hinge region of the viral L (large) protein (RNA-dependent RNA polymerase) attenuates a wild-type canine distemper virus. Moreover, we show that single intranasal immunization with this recombinant virus provides significant protection against challenge with the virulent parental virus. Protection against wild-type challenge was gained either after recovery of cellular immunity postimmunization or after development of neutralizing antibodies. Insertion of EGFP seems to result in overattenuation of the virus, while our previous experiments demonstrated that the insertion of an epitope tag into a similar position did not affect L protein function. Thus, a desirable level of attenuation could be reached by manipulating the length of the insert (in the second hinge region of the L protein), providing additional tools for optimization of controlled attenuation. This strategy for controlled attenuation may be useful for a "quick response" in vaccine development against well-known and "new" viral infections and could be combined efficiently with other strategies of vaccine development and delivery systems.

  1. Canine distemper virus infection: proliferation of canine footpad keratinocytes.

    PubMed

    Gröne, A; Engelhardt, P; Zurbriggen, A

    2003-09-01

    The proliferation of footpad keratinocytes of canine distemper virus (CDV)-infected dogs was investigated. Footpads of 19 dogs inoculated experimentally with a virulent distemper strain (A75/17) and of two noninoculated control dogs were collected at necropsy. Dogs were divided into four groups according to results of the postmortem examination: dogs with severe distemper (group 1), dogs with mild distemper (group 2), inoculated dogs without distemper (group 3) and noninoculated dogs (group 4). There was no distinct difference of epidermal thickness among the four groups. Infection of the footpad epidermis with CDV was demonstrated using immunohistochemistry for viral nucleoprotein and in situ hybridization for nucleoprotein messenger ribonucleic acid (mRNA). Only group 1 dogs had viral antigen and mRNA in the footpad epidermis with the same distribution. Footpad epidermis of group 1 dogs had more mitotic figures in the basal layer, and significantly more basal keratinocytes were positive for the proliferation markers Ki-67 and proliferating cell nuclear antigen. Double-staining for Ki-67 and viral nucleoprotein identified rare double-labeled basal keratinocytes. These findings suggest that the presence of CDV particles in the footpad epidermis is associated with keratinocyte proliferation.

  2. Canine distemper virus infection of canine footpad epidermis.

    PubMed

    Gröne, Andrea; Doherr, Marcus G; Zurbriggen, Andreas

    2004-06-01

    Infection of the footpad epidermis can occur in natural canine distemper virus (CDV) infection of dogs. Footpads from 19 dogs experimentally inoculated with virulent distemper strain A75/17 and from two nonexposed dogs were examined histopathologically and assessed for the presence of viral antigen and nucleoprotein mRNA, as well as number of inflammatory and apoptotic cells. Dogs were divided into four groups based on inoculation status and postmortem examination: inoculated dogs with severe distemper (group 1, n = 7); inoculated dogs with mild distemper (group 2, n = 4); inoculated dogs without distemper (group 3, n = 8); and noninoculated dogs (group 4, n = 2). Footpads from dogs of all groups had a comparably thick epidermis. Eosinophilic viral inclusions and syncytial cells were present in footpad epidermis of one dog of group 1. Footpads of group 1 dogs contained viral antigen and mRNA in the epidermis with strongest staining in a subcorneal location. Additionally, in these dogs footpad dermal structures including eccrine glands and vascular walls were positive for virus particles. No CDV antigen or mRNA was present in the footpad epidermis and dermis of any other dog. Group 1 dogs had more CD3-positive cells and apoptotic cells within the basal layer of the epidermis when compared to the other groups. These findings demonstrate that in experimental infection CDV antigen and mRNA were colocalized in all layers of the infected canine footpad epidermis. The scarcity of overt pathological reactions with absence of keratinocyte degeneration indicates a noncytocidal persisting infection of footpad keratinocytes by CDV.

  3. Canine distemper virus strains circulating among North American dogs.

    PubMed

    Kapil, Sanjay; Allison, Robin W; Johnston, Larry; Murray, Brandy L; Holland, Steven; Meinkoth, Jim; Johnson, Bill

    2008-04-01

    Canine distemper virus (CDV) is a highly contagious virus that causes multisystemic disease in dogs. We received seven samples from dogs with CD from the United States during 2007. CDV isolates from these samples formed large, multinucleated syncytia in a Vero cell line expressing canine signaling lymphocyte activation molecule (SLAM). Based on the hemagglutinin gene sequences, the CDV isolates from three states (California, Missouri, and Oklahoma) formed two CDV genetic groups: group I (major; six of seven isolates) consisted of CDV isolates closely related to the European wildlife lineage of CDV, and group II (minor; one of seven isolates) was genetically related to the Arctic-like lineage of CDV. However, both CDV groups were genetically different from the current vaccine strains that belong to the American-1 lineage of the old (1930 to 1950) CDV isolates.

  4. Uncommon acute neurologic presentation of canine distemper in 4 adult dogs

    PubMed Central

    Galán, Alba; Gamito, Araceli; Carletti, Beatrice E.; Guisado, Alicia; de las Mulas, Juana Martín; Pérez, José; Martín, Eva M.

    2014-01-01

    Four uncommon cases of canine distemper (CD) were diagnosed in vaccinated adult dogs. All dogs had acute onset of neurologic signs, including seizures, abnormal mentation, ataxia, and proprioceptive deficits. Polymerase chain reaction for CD virus was positive on cerebrospinal fluid in 2 cases. Due to rapid deterioration the dogs were euthanized and CD was confirmed by postmortem examination. PMID:24688139

  5. Optic neuritis caused by canine distemper virus in a Jack Russell terrier.

    PubMed

    Richards, Tara R; Whelan, Nick C; Pinard, Chantale L; Alcala, Fernanda Castillo; Wolfe, Katheryn C

    2011-04-01

    An atypical case of canine distemper (CD) was diagnosed in a vaccinated healthy adult dog. The patient was presented circling, seizuring, and blind. Postmortem examination resulted in a diagnosis of CD. Optic neuritis was diagnosed, a finding not previously described in the context of CD virus infection presenting solely with neurological signs.

  6. Uncommon acute neurologic presentation of canine distemper in 4 adult dogs.

    PubMed

    Galán, Alba; Gamito, Araceli; Carletti, Beatrice E; Guisado, Alicia; de las Mulas, Juana Martín; Pérez, José; Martín, Eva M

    2014-04-01

    Four uncommon cases of canine distemper (CD) were diagnosed in vaccinated adult dogs. All dogs had acute onset of neurologic signs, including seizures, abnormal mentation, ataxia, and proprioceptive deficits. Polymerase chain reaction for CD virus was positive on cerebrospinal fluid in 2 cases. Due to rapid deterioration the dogs were euthanized and CD was confirmed by postmortem examination.

  7. Humoral and cell-mediated immune responses in DNA immunized mink challenged with wild-type canine distemper virus.

    PubMed

    Nielsen, Line; Søgaard, Mette; Karlskov-Mortensen, Peter; Jensen, Trine Hammer; Jensen, Tove Dannemann; Aasted, Bent; Blixenkrone-Møller, Merete

    2009-07-30

    The aim of the study was to investigate the different phases of the immune response after DNA immunization with the hemagglutinin and nucleoprotein genes from canine distemper virus (CDV). Although attenuated live CDV vaccines have effectively reduced the incidence of disease, canine distemper is still a problem worldwide. The broad host range of CDV creates a constant viral reservoir among wildlife animals. Our results demonstrated early humoral and cell-mediated immune responses (IFN-gamma) in DNA vaccinated mink compared to mock-vaccinated mink after challenge with a Danish wild-type CDV. The DNA vaccine-induced immunity protected the natural host against disease development.

  8. Prevalence of positive antibody test results for canine parvovirus (CPV) and canine distemper virus (CDV) and response to modified live vaccination against CPV and CDV in dogs entering animal shelters.

    PubMed

    Litster, Annette; Nichols, Jamieson; Volpe, Allison

    2012-05-25

    Canine parvovirus (CPV) and canine distemper virus (CDV) infections are relatively common in animal shelters and are important population management issues since the immune status of incoming dogs is usually unknown. This study aimed to determine the prevalence of positive antibody test results for CPV and CDV in incoming dogs aged ≥ 4 months and to measure antibody response over 2 weeks following vaccination with a modified live vaccine (MLV). Dogs aged 4-24 months entering an adoption-guarantee shelter (Shelter 1, n=51) and aged ≥ 4 months entering a limited admission shelter (Shelter 2; n=51) were enrolled. Dogs from Shelter 1 had been vaccinated with MLV at a municipal shelter 5 days before enrollment, whereas dogs from Shelter 2 had no known history of vaccination at enrollment. Sera were obtained on day 1, immediately prior to CPV/CDV MLV, and tested using an in-clinic ELISA kit to detect CPV/CDV antibodies. Dogs negative for CPV and/or CDV were retested at day 6-8 and those dogs still negative at day 6-8 were retested at day 13-15. Prior to CPV/CDV MLV on day 1, more dogs tested positive for CPV (Shelter 1 - 68.6%; Shelter 2 - 84.3%) than for CDV (Shelter 1 - 37.3%; Shelter 2 - 41.2%). On day 1, prior to MLV, all spayed/neutered animals tested CPV antibody-positive (n=17/102) and CPV antibody-positive dogs were older than serologically negative dogs (Shelter 1, P=0.0029; Shelter 2, P=0.0042). By day 13-15, almost all dogs were CPV antibody-positive (Shelter 1 - 97.9%; Shelter 2 - 100.0%) and CDV antibody-positive (Shelter 1 - 93.8%; Shelter 2 - 97.8%). MLV induces protective antibody titers against CPV/CDV in almost all dogs after 13-15 days.

  9. Antigenic differences in the H proteins of canine distemper viruses.

    PubMed

    Iwatsuki, K; Tokiyoshi, S; Hirayama, N; Nakamura, K; Ohashi, K; Wakasa, C; Mikami, T; Kai, C

    2000-02-01

    Antigenic properties between new Japanese field isolates and vaccine strains of canine distemper virus (CDV) have been compared using four monoclonal antibodies (MAbs) (JD-5, JD-7, JD-11 and d-7) against the hemagglutinin (H) proteins of CDV. JD-5, JD-7 and JD-11 are newly established antibodies. Three MAbs, namely d-7, JD-5 and JD-11, reacted similarly to all the CDV strains examined. However, JD-7 reacted much more strongly with the vaccine strains and an old field isolate than the recent field isolates in immunofluorescence, radio immunoprecipitation and virus neutralization assays. These results indicate that an antigenic region in the H protein, concerned with neutralization and recognized by JD-7, has been altered in the recent field isolates.

  10. Development of a combined canine distemper virus specific RT-PCR protocol for the differentiation of infected and vaccinated animals (DIVA) and genetic characterization of the hemagglutinin gene of seven Chinese strains demonstrated in dogs.

    PubMed

    Yi, Li; Cheng, Shipeng; Xu, Hongli; Wang, Jianke; Cheng, Yuening; Yang, Shen; Luo, Bin

    2012-01-01

    A combined reverse-transcription polymerase chain reaction (RT-PCR) method was developed for the detection and differentiation of wild-type and vaccine strains of the canine distemper virus (CDV). A pair of primers (P1/P2) was used to detect both CDV wild-type strains and vaccines. Another pair (P3/P4) was used to detect only CDV wild-type strains. A 335bp fragment was amplified from the genomic RNA of the vaccine and wild-type strains. A 555bp fragment was amplified specifically from the genomic RNA of the wild-type strains. No amplification was achieved for the uninfected cells, cells infected with canine parvovirus, canine coronavirus, or canine adenovirus. The combined RT-PCR method detected effectively and differentiated the CDV wild-type and vaccine strains by two separate RT-PCRs. The method can be used for clinical detection and epidemiological surveillance. The phylogenetic analysis of the hemagglutinin gene of the local wild-type CDV strains revealed that the seven local isolates all belonged to the Asia-1 lineage, and were clustered closely with one another at the same location. These results suggested that the CDV genotype Asia-1 is circulating currently in domestic dogs in China.

  11. Canine Distemper in Endangered Ethiopian Wolves

    PubMed Central

    Gordon, Christopher H.; Hussein, Alo; Laurenson, M. Karen; Malcolm, James R.; Marino, Jorgelina; Regassa, Fekede; Stewart, Anne-Marie E.; Fooks, Anthony R.; Sillero-Zubiri, Claudio

    2015-01-01

    The Ethiopian wolf (Canis simensis) is the world’s rarest canid; ≈500 wolves remain. The largest population is found within the Bale Mountains National Park (BMNP) in southeastern Ethiopia, where conservation efforts have demonstrated the negative effect of rabies virus on wolf populations. We describe previously unreported infections with canine distemper virus (CDV) among these wolves during 2005–2006 and 2010. Death rates ranged from 43% to 68% in affected subpopulations and were higher for subadult than adult wolves (83%–87% vs. 34%–39%). The 2010 CDV outbreak started 20 months after a rabies outbreak, before the population had fully recovered, and led to the eradication of several focal packs in BMNP’s Web Valley. The combined effect of rabies and CDV increases the chance of pack extinction, exacerbating the typically slow recovery of wolf populations, and represents a key extinction threat to populations of this highly endangered carnivore. PMID:25898177

  12. Canine distemper in endangered Ethiopian wolves.

    PubMed

    Gordon, Christopher H; Banyard, Ashley C; Hussein, Alo; Laurenson, M Karen; Malcolm, James R; Marino, Jorgelina; Regassa, Fekede; Stewart, Anne-Marie E; Fooks, Anthony R; Sillero-Zubiri, Claudio

    2015-05-01

    The Ethiopian wolf (Canis simensis) is the world's rarest canid; ≈500 wolves remain. The largest population is found within the Bale Mountains National Park (BMNP) in southeastern Ethiopia, where conservation efforts have demonstrated the negative effect of rabies virus on wolf populations. We describe previously unreported infections with canine distemper virus (CDV) among these wolves during 2005-2006 and 2010. Death rates ranged from 43% to 68% in affected subpopulations and were higher for subadult than adult wolves (83%-87% vs. 34%-39%). The 2010 CDV outbreak started 20 months after a rabies outbreak, before the population had fully recovered, and led to the eradication of several focal packs in BMNP's Web Valley. The combined effect of rabies and CDV increases the chance of pack extinction, exacerbating the typically slow recovery of wolf populations, and represents a key extinction threat to populations of this highly endangered carnivore.

  13. Identification of a new genotype of canine distemper virus circulating in America.

    PubMed

    Gámiz, César; Martella, Vito; Ulloa, Raúl; Fajardo, Raúl; Quijano-Hernandéz, Israel; Martínez, Simón

    2011-08-01

    Canine Distemper is a highly contagious viral systemic disease that affects a wide variety of terrestrial carnivores. Canine Distemper virus (CDV) appears genetically heterogeneous, markedly in the hemagglutinin protein (H), showing geographic patterns of diversification that are useful to monitor CDV molecular epidemiology. In Mexico the activity of canine distemper remains high in dogs, likely because vaccine prophylaxis coverage in canine population is under the levels required to control effectively the disease. By phylogenetic analysis based on the nucleoprotein (N) and on the H genes, Mexican CDV strains collected between 2007 and 2010 were distinguished into several genovariants, all which constituted a unique group, clearly distinct from field and vaccine strains circulating worldwide, but resembling a CDV strain, 19876, identified in Missouri, USA, 2004, that was genetically unrelated to other North-American CDV strains. Gathering information on the genetic heterogeneity of CDV on a global scale appears pivotal in order to investigate the origin and modalities of introduction of unusual/novel CDV strains, as well as to understand if vaccine breakthroughs or disease epidemics may be somewhat related to genetic/antigenic or biological differences between field and vaccine strains.

  14. 9 CFR 113.302 - Distemper Vaccine-Mink.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Distemper Vaccine-Mink. 113.302... Virus Vaccines § 113.302 Distemper Vaccine—Mink. Distemper Vaccine—Mink shall be prepared from virus... immunogenic shall be used for preparing the production seed virus for vaccine production. All serials...

  15. 9 CFR 113.302 - Distemper Vaccine-Mink.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Distemper Vaccine-Mink. 113.302... Virus Vaccines § 113.302 Distemper Vaccine—Mink. Distemper Vaccine—Mink shall be prepared from virus... immunogenic shall be used for preparing the production seed virus for vaccine production. All serials...

  16. 9 CFR 113.302 - Distemper Vaccine-Mink.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Distemper Vaccine-Mink. 113.302... Virus Vaccines § 113.302 Distemper Vaccine—Mink. Distemper Vaccine—Mink shall be prepared from virus... immunogenic shall be used for preparing the production seed virus for vaccine production. All serials...

  17. 9 CFR 113.302 - Distemper Vaccine-Mink.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Distemper Vaccine-Mink. 113.302... Virus Vaccines § 113.302 Distemper Vaccine—Mink. Distemper Vaccine—Mink shall be prepared from virus... immunogenic shall be used for preparing the production seed virus for vaccine production. All serials...

  18. 9 CFR 113.302 - Distemper Vaccine-Mink.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Distemper Vaccine-Mink. 113.302... Virus Vaccines § 113.302 Distemper Vaccine—Mink. Distemper Vaccine—Mink shall be prepared from virus... immunogenic shall be used for preparing the production seed virus for vaccine production. All serials...

  19. Immunization of puppies in the presence of maternally derived antibodies against canine distemper virus.

    PubMed

    Pardo, M C; Tanner, P; Bauman, J; Silver, K; Fischer, L

    2007-07-01

    Vaccination of dams with modified-live canine distemper virus (CDV) vaccines will elicit high concentrations of colostral antibody, that although vital for protection of the pup during the first weeks of life, can interfere with active vaccination against the virus. In the present study, 12 pups, 7-9 weeks of age, with maternally derived immunity to CDV, were vaccinated with a canarypox-vectored CDV vaccine. These pups were protected against intravenous challenge with CDV. Three littermate pups that were unvaccinated all developed clinical signs of infection after challenge, and two of these control pups died.

  20. An unusual presentation of canine distemper virus infection in a domestic ferret (Mustela putorius furo).

    PubMed

    Zehnder, Ashley M; Hawkins, Michelle G; Koski, Marilyn A; Luff, Jennifer A; Benak, Jaromir; Lowenstine, Linda J; White, Stephen D

    2008-08-01

    A 4.5-year-old, male castrated ferret was examined with a 27-day history of severe pruritus, generalized erythema and scaling. Skin scrapings and a trichogram were negative for mites and dermatophyte organisms. A fungal culture of hair samples was negative. The ferret was treated presumptively for scabies and secondary bacterial and yeast infection with selamectin, enrofloxacin, fluconazole, diphenhydramine and a miconazole-chlorhexidine shampoo. The ferret showed mild improvement in clinical signs over the subsequent 3 weeks, but was inappetent and required supportive feeding and subcutaneous fluids by the owner. The ferret was then examined on an emergency basis at the end of 3 weeks (53 days following initial signs of illness) for severe blood loss from a haematoma over the interscapular region, hypotension and shock. The owners elected euthanasia due to a poor prognosis and deteriorating condition. On post-mortem examination intraepithelial canine distemper viral inclusions were identified systemically, and abundant canine distemper virus antigen was identified with immunohistochemical staining. It is important to note the prolonged course of disease along with the absence of respiratory and neurological signs because this differs from the classic presentation of canine distemper virus infection in ferrets. Canine distemper virus should remain a clinical suspicion for ferrets with skin lesions that do not respond to appropriate therapy, even in animals that were previously vaccinated.

  1. Genetic diversity of Hungarian canine distemper virus strains.

    PubMed

    Demeter, Zoltán; Lakatos, Béla; Palade, Elena Alina; Kozma, Tamás; Forgách, Petra; Rusvai, Miklós

    2007-06-21

    To achieve proper diagnosis of dogs based on acute clinical symptoms and poorly preserved field samples taken from animals that died due to canine distemper (CD), a new differential diagnostic test has been developed based on polymerase chain reaction (PCR). In this study, more than 150 samples collected from dogs showing respiratory, gastrointestinal and neurological signs suggesting canine distemper virus (CDV) infection were examined. The samples consisted of urine, blood and nasal swabs collected from clinically ill patients, sent to our laboratory by clinicians from various veterinary clinics throughout Hungary. Various organs collected during the necropsy of dogs with pathological changes that suggested CDV infection were also included. Three distinct PCRs were designed. For diagnostic purposes, a primer pair specific to a 409 bases-long segment within the conservative part of the large polymerase region (L) of the CDV genome was designed. Using this test, out of the 150 analyzed samples, 46 (30.66%) proved to be positive for CDV, indicating that CDV still represents a high risk to the canine population in Hungary. For the phylogenetical analysis, a primer pair that completely encompasses the hemagglutinin (H) gene of the CDV genome was designed. The amplicons of this region were sequenced in both directions using the appropriate primers. Our results indicate that several different CDV genotypes are currently present in Hungary. Nine of the analyzed Hungarian strains turned out to belong to the so-called Arctic group of CDVs, and were most closely related to non-European strains from North America, China and Greenland, as well as to the phocine distemper virus 2 (PDV-2) isolated from Baikal seals (Phoca sibirica). One of the Hungarian strains showed high similarity to other European isolates from Denmark, Germany, Italy and Turkey, as well as to other isolates from geographically more distant regions, such as the USA. Three Hungarian strains seem to join a

  2. Canine distemper and related diseases: report of a severe outbreak in a kennel.

    PubMed

    Decaro, N; Camero, M; Greco, G; Zizzo, N; Tinelli, A; Campolo, M; Pratelli, A; Buonavoglia, C

    2004-04-01

    An outbreak of canine distemper in a kennel of German shepherds in the province of Bari is reported. Six 42-day-old pups developed typical signs of canine distemper (fever, conjunctivitis, respiratory distress and enteritis) and died within 7-10 days. Neurological symptoms were observed only in one pup. Four additional pups, which had shown no sign of illness, were separated and vaccinated, but two of these developed a severe, fatal nervous form 15 days later. Post-mortem examination, carried out on two pups which died without neurological signs, showed pneumonia and enteritis, more severe in one of the two examined pups. Smears from the brain and the conjunctiva of both dogs tested positive for canine distemper virus (CDV) by an immunofluorescent assay, confirmed by the identification of viral RNA using RT-PCR. Bordetella bronchiseptica and a canine adenovirus strain, characterized as canine adenovirus type 2 by a differential PCR assay, were isolated from the lungs of the pup showing the most pronounced lesions. Furthermore, canine coronavirus was detected by PCR in the intestinal content of this pup, suggesting a multifactorial aetiology of the outbreak.

  3. Magnetic resonance imaging findings in acute canine distemper virus infection.

    PubMed

    Bathen-Noethen, A; Stein, V M; Puff, C; Baumgaertner, W; Tipold, A

    2008-09-01

    Demyelination is the prominent histopathological hallmark in the acute stage of canine distemper virus infection. Magnetic resonance imaging is an important diagnostic tool in human beings to determine demyelination in the brain, for example in multiple sclerosis. Five young dogs with clinically suspected canine distemper virus infection were subjected to magnetic resonance imaging of the brain and histopathological and immunohistochemical examinations. Hyperintense lesions and loss of contrast between grey and white matter were detected in T2-weighted images in the cerebellum and/or in the brainstem of three dogs, which correlated with demyelination demonstrated in histopathological examination. Furthermore, increased signal intensities in T2-weighted images were seen in the temporal lobe of four dogs with no evidence of demyelination. Magnetic resonance imaging seems to be a sensitive tool for the visualisation of in vivo myelination defects in dogs with acute canine distemper virus infection. Postictal oedema and accumulation of antigen positive cells have to be considered an important differential diagnosis.

  4. Detection of canine distemper virus antigen in canine serum and its application to diagnosis.

    PubMed

    Soma, T; Ishii, H; Hara, M; Ohe, K; Hagimori, I; Ishikawa, Y; Taneno, A

    2003-10-18

    Canine distemper virus (CDV) antigen was detected in the serum of dogs by an ELISA and the results of this assay were compared with an anti-CDV immunoglobulin M (IgM) antibody test. In paired sera from 26 naturally infected dogs, the antigen-positive rate was 26.9 per cent at the first examination and 11.5 per cent at the second examination two to three weeks later. The antigen was detected in three of the 10 dogs which were negative for anti-CDV IgM antibody at the first examination. It could also be detected in the serum of between eight and two of 40 specific pathogen-free dogs vaccinated against CDV, for up to four weeks after they were vaccinated.

  5. [Genetic variations and cellular receptors of Canine distemper virus--a review].

    PubMed

    Zhao, Jianjun; Yan, Xijun; Wu, Wei

    2008-07-01

    Canine distemper (CD) caused by Canine distemper virus (CDV) was first reported in 1905, and has been one of the most serious contagious diseases of dogs as well as other carnivores. Recently, increasing cases of canine distemper (CD) both in vaccinated and unvaccinated dogs and in wildlife have been reported in Japan, America, Europe and Africa. Based on phylogenetic analysis of the hemagglutinin (H) gene sequences, six genotypes of CDV were distinguished. Antigenic heterogeneity of the H protein that provides an important protective antigen against CDV infection has been observed between wild-type CDV and vaccine strains. So it was suspected that the vaccines currently used can no longer efficiently protect animal from present-day circulating CDV infection. The host range of CDV includes all species of the families Canidae and many other species. Both signaling lymphocyte activation molecule (SLAM) and heparin sulfate (HS) expressed on the cells of the immune system or other non-lymphoid tissues can act as the cellular receptors for CDV, and are one of the major determinants of the host range and tissue tropism. In this review, we discussed the above-mentioned issues based on the recent research progress and the studies in our laboratory.

  6. Genotypic lineages and restriction fragment length polymorphism of canine distemper virus isolates in Thailand.

    PubMed

    Radtanakatikanon, Araya; Keawcharoen, Juthatip; Charoenvisal, Na Taya; Poovorawan, Yong; Prompetchara, Eakachai; Yamaguchi, Ryoji; Techangamsuwan, Somporn

    2013-09-27

    Canine distemper virus (CDV) is known to cause multisystemic disease in all families of terrestrial carnivores. Attenuated live vaccines have been used to control CDV in a variety of species for many decades, yet a number of CDV infections in vaccinated dogs are still observed. The aims of this study were to investigate the genetic diversity of CDV lineages based on phosphoprotein (P), hemagglutinin (H) and fusion protein (F) genes and to develop the restriction fragment length polymorphism (RFLP) technique for effective differentiation among individual wild-type and vaccine lineages in Thailand. Four commercial vaccine products, thirteen conjunctival swabs and various tissues from 9 necropsied dogs suspected of having CDV infections were included. Virus isolation was performed using Vero cell expressing canine signaling lymphocyte activation molecules (Vero-DST cells). Reverse-transcription polymerase chain reaction (RT-PCR) on 3 gene regions from the dog derived specimens and the vaccines were carried out, then RFLP analysis upon F-gene amplified fragments was developed. Nucleotide sequence and phylogenetic analysis were compared with other CDV lineages in Genbank. Phylogenetic relationships revealed that CDV field isolates were separated from the vaccine lineage and could be divided into two clusters; one of which belonged to the Asia-1 lineage and another, not related to any previous recognized lineages was proposed as 'Asia-4'. RFLP patterns demonstrating concordance with phylogenetic trees of the distemper virus allowed for differentiation between the Asia-1, Asia-4 and vaccine lineages. Thus, RFLP technique is able to effectively distinguish individual wild-type canine distemper virus from vaccine lineages in Thailand.

  7. [Immunosuppression in dogs and pigs infected with canine distemper virus].

    PubMed

    Sereda, A D; Nogina, I V

    2011-01-01

    Immunosuppression manifesting itself as leukopenia and a considerably lower lymphocyte proliferative response to T- and B-cell mitogens develops in pigs and dogs within 2-3 weeks after intramuscular or oral infection with canine distemper virus (CDV). CDV antigens are detectable in the oral secretions of the animals within 2-2.5 week after infection.

  8. Fatal canine distemper virus infection of giant pandas in China.

    PubMed

    Feng, Na; Yu, Yicong; Wang, Tiecheng; Wilker, Peter; Wang, Jianzhong; Li, Yuanguo; Sun, Zhe; Gao, Yuwei; Xia, Xianzhu

    2016-06-16

    We report an outbreak of canine distemper virus (CDV) infection among endangered giant pandas (Ailuropoda melanoleuca). Five of six CDV infected giant pandas died. The surviving giant panda was previously vaccinated against CDV. Genomic sequencing of CDV isolated from one of the infected pandas (giant panda/SX/2014) suggests it belongs to the Asia-1 cluster. The hemagglutinin protein of the isolated virus and virus sequenced from lung samples originating from deceased giant pandas all possessed the substitutions V26M, T213A, K281R, S300N, P340Q, and Y549H. The presence of the Y549H substitution is notable as it is found at the signaling lymphocytic activation molecule (SLAM) receptor-binding site and has been implicated in the emergence of highly pathogenic CDV and host switching. These findings demonstrate that giant pandas are susceptible to CDV and suggest that surveillance and vaccination among all captive giant pandas are warranted to support conservation efforts for this endangered species.

  9. Canine distemper virus causes apoptosis of Vero cells.

    PubMed

    Guo, A; Lu, C

    2000-04-01

    Apoptosis of Vero cells infected with two canine distemper virus (CDV) vaccine strains was detected using TdT (terminal deoxynucleotidyl transferase)-mediated dUTP nick end-labelling (TUNEL), flow cytometric analysis, agarose gel electrophoresis and electron microscopy (EM). By TUNEL, apoptotic cells were found in CDV-Onderstepoort (CDV-Ond)-infected cells. DNA fragments isolated from infected cells were separated by agarose gel electrophoresis and a 'ladder' pattern appeared. EM observations demonstrated that the cells undergoing cytopathic effect (CPE) possessed morphological characteristics of apoptotic cells. Flow cytometric analysis indicated that CDV could induce apoptosis of Vero cells, but the percentages of the apoptotic cells were correlated with the CPE types. The strain showing the cell-rounding type of CPE produced a much higher percentage of apoptotic cells than CDV-Ond with the syncytium type of CPE (P < 0.01). It was concluded that CDV vaccine strains could induce apoptosis of Vero cells and the apoptosis was virus strain-dependent and cell-dependent. The mechanism remains to be studied.

  10. Fatal canine distemper virus infection of giant pandas in China

    PubMed Central

    Feng, Na; Yu, Yicong; Wang, Tiecheng; Wilker, Peter; Wang, Jianzhong; Li, Yuanguo; Sun, Zhe; Gao, Yuwei; Xia, Xianzhu

    2016-01-01

    We report an outbreak of canine distemper virus (CDV) infection among endangered giant pandas (Ailuropoda melanoleuca). Five of six CDV infected giant pandas died. The surviving giant panda was previously vaccinated against CDV. Genomic sequencing of CDV isolated from one of the infected pandas (giant panda/SX/2014) suggests it belongs to the Asia-1 cluster. The hemagglutinin protein of the isolated virus and virus sequenced from lung samples originating from deceased giant pandas all possessed the substitutions V26M, T213A, K281R, S300N, P340Q, and Y549H. The presence of the Y549H substitution is notable as it is found at the signaling lymphocytic activation molecule (SLAM) receptor-binding site and has been implicated in the emergence of highly pathogenic CDV and host switching. These findings demonstrate that giant pandas are susceptible to CDV and suggest that surveillance and vaccination among all captive giant pandas are warranted to support conservation efforts for this endangered species. PMID:27310722

  11. Genotyping of canine distemper virus strains circulating in Brazil from 2008 to 2012.

    PubMed

    Budaszewski, Renata da Fontoura; Pinto, Luciane Dubina; Weber, Matheus Nunes; Caldart, Eloiza Teles; Alves, Christian Diniz Beduschi Travassos; Martella, Vito; Ikuta, Nilo; Lunge, Vagner Ricardo; Canal, Cláudio Wageck

    2014-02-13

    Canine distemper virus (CDV) is a major pathogen of dogs and represents a serious threat to both unvaccinated and vaccinated animals. This study surveyed dogs with or without clinical signs related to canine distemper from different regions of Brazil from 2008 to 2012. A total of 155 out of 386 animals were found to be CDV positive by RT-PCR; 37 (23.8%) dogs were asymptomatic at the time of sampling, and 90 (58%) displayed clinical signs suggestive of distemper. Nineteen (12.2%) dogs had a record of complete vaccination, 15 (9.6%) had an incomplete vaccination protocol, and 76 (49%) had no vaccination record. Based on the sequence analysis of the complete hemagglutinin gene of 13 samples, 12 of the strains were characterized as Genotype South America-I/Europe. Considering criteria of at least 95% nucleotide identity to define a genotype and 98% to define a subgenotype, South America-I/Europe sequences segregated into eight different phylogenetically well-defined clusters that circulated or co-circulated in distinct geographical areas. Together, these findings highlight the relevance of CDV infection in Brazilian dogs, demonstrate the predominance of one genotype in Brazil and support the need to intensify the current control measures.

  12. Canine distemper outbreak in pet store puppies linked to a high-volume dog breeder.

    PubMed

    Schumaker, Brant A; Miller, Myrna M; Grosdidier, Paul; Cavender, Jacqueline L; Montgomery, Donald L; Cornish, Todd E; Farr, Robert M; Driscoll, Michael; Maness, Lori J; Gray, Tangney; Petersen, Dana; Brown, William L; Logan, Jim; O'Toole, Donal

    2012-11-01

    Canine distemper is uncommon in the pet trade in the United States, in large part due to effective vaccines against Canine distemper virus (CDV). This is a report of CDV affecting 24 young dogs of multiple breeds shortly after sale by 2 pet stores in Wyoming during August-October 2010. Cases were diagnosed over 37 days. Diagnosis was established by a combination of fluorescent antibody staining, reverse transcription polymerase chain reaction, negative stain electron microscopy, and necropsy with histopathology. Viral hemagglutinin gene sequences were analyzed from 2 affected dogs and were identical (GenBank accession no. JF283477). Sequences were distinct from those in a contemporaneous unrelated case of CDV in a Wyoming dog (JF283476) that had no contact with the pet store dogs. The breeding property from which the puppies originated was quarantined by the Kansas Animal Health Department. Puppies intended for sale were tested for CDV. Canine distemper was diagnosed on site in November 2010. At that point 1,466 dogs were euthanized to eliminate dispersal of the disease through commercial channels. The investigation underscores the risks inherent in large-scale dog breeding when vaccination and biosecurity practices are suboptimal.

  13. Serological detection of infection with canine distemper virus, canine parvovirus and canine adenovirus in communal dogs from Zimbabwe.

    PubMed

    McRee, Anna; Wilkes, Rebecca P; Dawson, Jessica; Parry, Roger; Foggin, Chris; Adams, Hayley; Odoi, Agricola; Kennedy, Melissa A

    2014-09-05

    Domestic dogs are common amongst communities in sub-Saharan Africa and may serve as important reservoirs for infectious agents that may cause diseases in wildlife. Two agents of concern are canine parvovirus (CPV) and canine distemper virus (CDV), which may infect and cause disease in large carnivore species such as African wild dogs and African lions, respectively. The impact of domestic dogs and their diseases on wildlife conservation is increasing in Zimbabwe, necessitating thorough assessment and implementation of control measures. In this study, domestic dogs in north-western Zimbabwe were evaluated for antibodies to CDV, CPV, and canine adenovirus (CAV). These dogs were communal and had no vaccination history. Two hundred and twenty-five blood samples were collected and tested using a commercial enzyme-linked immunosorbent assay (ELISA) for antibodies to CPV, CDV, and CAV. Of these dogs, 75 (34%) had detectable antibodies to CDV, whilst 191 (84%) had antibodies to CPV. Antibodies to canine adenovirus were present in 28 (13%) dogs. Canine parvovirus had high prevalence in all six geographic areas tested. These results indicate that CPV is circulating widely amongst domestic dogs in the region. In addition, CDV is present at high levels. Both pathogens can infect wildlife species. Efforts for conservation of large carnivores in Zimbabwe must address the role of domestic dogs in disease transmission.

  14. Characterization of a new dog isolate of canine distemper virus from China.

    PubMed

    Qiao, J; Meng, Q; Chen, C; Xia, X; Cai, X; Ren, Y; Zhang, H

    2011-01-01

    Canine distemper virus (CDV) is a highly contagious pathogen of dogs. Vaccination is an effective way to protect dogs from CDV infection, but occasionally fails. In the present study, a wild type (wt) CDV, named XJ2, was isolated from a dead vaccinated dog. The hemagglutinin (H) gene of the XJ2 was amplified and analyzed for the molecular characteristics including N-glycosylation sites, phylogenesis, hydrophobicity and epitopes. The data indicated that XJ2 was a genetic variant strain of CDV. CDV-sero-negative dogs were inoculated intranasally with XJ2, developed severe clinical symptoms and died, suggesting high virulence.

  15. Establishment of a rescue system for canine distemper virus.

    PubMed

    Gassen, U; Collins, F M; Duprex, W P; Rima, B K

    2000-11-01

    Canine distemper virus (CDV) has been rescued from a full-length cDNA clone. Besides Measles virus (MV) and Rinderpest virus, a third morbillivirus is now available for genetic analysis using reverse genetics. A plasmid p(+)CDV was constructed by sequential cloning using the Onderstepoort vaccine strain large-plaque-forming variant. The presence of a T7 promoter allowed transcription of full-length antigenomic RNA by a T7 RNA polymerase, which was provided by a host range mutant of vaccinia virus (MVA-T7). Plasmids expressing the nucleocapsid protein, the phosphoprotein, and the viral RNA-dependent RNA polymerase, also under control of a T7 promoter, have been generated. Infection of HeLa cells with MVA-T7 and subsequent transfection of p(+)CDV plus the helper plasmids led to syncytium formation and release of infectious recombinant (r) CDV. Comparison of the rescued virus with the parental virus revealed no major differences in the progression of infection or in the shape and size of syncytia. A genetic tag, consisting of two nucleotide changes within the coding region of the L protein, has been identified in the rCDV genome. Expression by rCDV of all the major viral structural proteins has been demonstrated by immunofluorescence.

  16. Differentiation of canine distemper virus isolates in fur animals from various vaccine strains by reverse transcription-polymerase chain reaction-restriction fragment length polymorphism according to phylogenetic relations in china.

    PubMed

    Wang, Fengxue; Yan, Xijun; Chai, Xiuli; Zhang, Hailing; Zhao, Jianjun; Wen, Yongjun; Wu, Wei

    2011-02-27

    In order to effectively identify the vaccine and field strains of Canine distemper virus (CDV), a new differential diagnostic test has been developed based on reverse transcription-polymerase chain reaction (RT-PCR) and restriction fragment length polymorphism (RFLP). We selected an 829 bp fragment of the nucleoprotein (N) gene of CDV. By RFLP analysis using BamHI, field isolates were distinguishable from the vaccine strains. Two fragments were obtained from the vaccine strains by RT-PCR-RFLP analysis while three were observed in the field strains. An 829 nucleotide region of the CDV N gene was analyzed in 19 CDV field strains isolated from minks, raccoon dogs and foxes in China between 2005 and 2007. The results suggest this method is precise, accurate and efficient. It was also determined that three different genotypes exist in CDV field strains in fur animal herds of the north of China, most of which belong to Asian type. Mutated field strains, JSY06-R1, JSY06-R2 and JDH07-F1 also exist in Northern China, but are most closely related to the standard virulent strain A75/17, designated in Arctic and America-2 genetype in the present study, respectively.

  17. Canine distemper virus in wild ferret-badgers of Taiwan.

    PubMed

    Chen, Chen-Chih; Pei, Kurtis Jai-Chyi; Liao, Ming-Huei; Mortenson, Jack A

    2008-04-01

    Canine distemper is an acute or subacute, highly contagious, febrile disease that is caused by canine distemper virus (CDV). Two CDV-infected wild Taiwan ferret-badgers (Melogale moschata subauantiaca) were found in Kaohsiung County, southern Taiwan, in 2005. Each case was confirmed by detecting CDV RNA in lung and brain tissues. A suspected third case was detected based on clinical signs and histology. These cases are the first record of wildlife infected by CDV in Taiwan. It is believed that domestic dogs or coexisting wild carnivores infected with the virus were the most likely source, and a serologic survey is needed to fully understand the host range of this virus in Taiwan. In addition, further genetic sequencing is needed to determine the source of these CDV cases.

  18. The hemagglutinin of canine distemper virus determines tropism and cytopathogenicity.

    PubMed

    von Messling, V; Zimmer, G; Herrler, G; Haas, L; Cattaneo, R

    2001-07-01

    Canine distemper virus (CDV) and measles virus (MV) cause severe illnesses in their respective hosts. The viruses display a characteristic cytopathic effect by forming syncytia in susceptible cells. For CDV, the proficiency of syncytium formation varies among different strains and correlates with the degree of viral attenuation. In this study, we examined the determinants for the differential fusogenicity of the wild-type CDV isolate 5804Han89 (CDV(5804)), the small- and large-plaque-forming variants of the CDV vaccine strain Onderstepoort (CDV(OS) and CDV(OL), respectively), and the MV vaccine strain Edmonston B (MV(Edm)). The cotransfection of different combinations of fusion (F) and hemagglutinin (H) genes in Vero cells indicated that the H protein is the main determinant of fusion efficiency. To verify the significance of this observation in the viral context, a reverse genetic system to generate recombinant CDVs was established. This system is based on a plasmid containing the full-length antigenomic sequence of CDV(OS). The coding regions of the H proteins of all CDV strains and MV(Edm) were introduced into the CDV and MV genetic backgrounds, and recombinant viruses rCDV-H(5804), rCDV-H(OL), rCDV-H(Edm), rMV-H(5804), rMV-H(OL), and rMV-H(OS) were recovered. Thus, the H proteins of the two morbilliviruses are interchangeable and fully functional in a heterologous complex. This is in contrast with the glycoproteins of other members of the family Paramyxoviridae, which do not function efficiently with heterologous partners. The fusogenicity, growth characteristics, and tropism of the recombinant viruses were examined and compared with those of the parental strains. All these characteristics were found to be predominantly mediated by the H protein regardless of the viral backbone used.

  19. Genetic characterization of an isolate of canine distemper virus from a Tibetan Mastiff in China.

    PubMed

    Li, Weike; Li, Tiansong; Liu, Yuxiu; Gao, Yuwei; Yang, Songtao; Feng, Na; Sun, Heting; Wang, Shengle; Wang, Lei; Bu, Zhigao; Xia, Xianzhu

    2014-08-01

    Canine distemper (CD) is a highly contagious, often fatal, multisystemic, and incurable disease in dogs and other carnivores, which is caused by canine distemper virus (CDV). Although vaccines have been used as the principal means of controlling the disease, CD has been reported in vaccinated animals. The hemoagglutinin (H) protein is one of the most important antigens for inducing protective immunity against CD, and antigenic variation of recent CDV strains may explain vaccination failure. In this study, a new CDV isolate (TM-CC) was obtained from a Tibetan Mastiff that died of distemper, and its genome was characterized. Phylogenetic analysis of the H gene revealed that the CDV-TM-CC strain is unique among 20 other CDV strains and can be classified into the Asia-1 group with the Chinese strains, Hebei and HLJ1-06, and the Japanese strain, CYN07-hV. The H gene of CDV-TM-CC shows low identity (90.4 % nt and 88.9 % aa) with the H gene of the classical Onderstepoort vaccine strain, which may explain the inability of the Tibetan Mastiff to mount a protective immune response. We also performed a comprehensive phylogenetic analysis of the N, P, and F protein sequences, as well as potential N-glycosylation sites and cysteine residues. This analysis shows that an N-glycosylation site at aa 108-110 within the F protein of CDV-TM-CC is specific for the wild-type strains (5804P, A75/17, and 164071) and the Asia-1 group strains, and may be another important factor for the poor immune response. These results provide important information for the design of CD vaccines in the China region and elsewhere.

  20. Inactivated Recombinant Rabies Viruses Displaying Canine Distemper Virus Glycoproteins Induce Protective Immunity against Both Pathogens.

    PubMed

    da Fontoura Budaszewski, Renata; Hudacek, Andrew; Sawatsky, Bevan; Krämer, Beate; Yin, Xiangping; Schnell, Matthias J; von Messling, Veronika

    2017-04-15

    The development of multivalent vaccines is an attractive methodology for the simultaneous prevention of several infectious diseases in vulnerable populations. Both canine distemper virus (CDV) and rabies virus (RABV) cause lethal disease in wild and domestic carnivores. While RABV vaccines are inactivated, the live-attenuated CDV vaccines retain residual virulence for highly susceptible wildlife species. In this study, we developed recombinant bivalent vaccine candidates based on recombinant vaccine strain rabies virus particles, which concurrently display the protective CDV and RABV glycoprotein antigens. The recombinant viruses replicated to near-wild-type titers, and the heterologous glycoproteins were efficiently expressed and incorporated in the viral particles. Immunization of ferrets with beta-propiolactone-inactivated recombinant virus particles elicited protective RABV antibody titers, and animals immunized with a combination of CDV attachment protein- and fusion protein-expressing recombinant viruses were protected from lethal CDV challenge. However, animals that were immunized with only a RABV expressing the attachment protein of CDV vaccine strain Onderstepoort succumbed to infection with a more recent wild-type strain, indicating that immune responses to the more conserved fusion protein contribute to protection against heterologous CDV strains.IMPORTANCE Rabies virus and canine distemper virus (CDV) cause high mortality rates and death in many carnivores. While rabies vaccines are inactivated and thus have an excellent safety profile and high stability, live-attenuated CDV vaccines can retain residual virulence in highly susceptible species. Here we generated recombinant inactivated rabies viruses that carry one of the CDV glycoproteins on their surface. Ferrets immunized twice with a mix of recombinant rabies viruses carrying the CDV fusion and attachment glycoproteins were protected from lethal CDV challenge, whereas all animals that received

  1. Canine parvovirus enteritis, canine distemper, and major histocompatibility complex genetic variation in Mexican wolves.

    PubMed

    Hedrick, Philip W; Lee, Rhonda N; Buchanan, Colleen

    2003-10-01

    The endangered Mexican wolf (Canis lupus baileyi) was recently reintroduced into Arizona and New Mexico (USA). In 1999 and 2000, pups from three litters that were part of the reintroduction program died of either canine parvovirus or canine distemper. Overall, half (seven of 14) of the pups died of either canine parvovirus or canine distemper. The parents and their litters were analyzed for variation at the class II major histocompatibility complex (MHC) gene DRB1. Similar MHC genes are related to disease resistance in other species. All six of the surviving pups genotyped for the MHC gene were heterozygous while five of the pups that died were heterozygous and one was homozygous. Resistance to pathogens is an important aspect of the management and long-term survival of endangered taxa, such as the Mexican wolf.

  2. Outbreak of canine distemper in domestic ferrets (Mustela putorius furo).

    PubMed

    Perpiñán, D; Ramis, A; Tomás, A; Carpintero, E; Bargalló, F

    2008-08-23

    In 2006 an outbreak of canine distemper affected 14 young domestic ferrets in Barcelona, Spain. Their clinical signs included a reduced appetite, lethargy, dyspnoea, coughing, sneezing, mucopurulent ocular and nasal discharges, facial and perineal dermatitis, diarrhoea, splenomegaly and fever. Late in the course of the disease, general desquamation and pruritus, and hyperkeratotic/crusting dermatitis of the lips, eyes, nose, footpads, and perineal area were observed. None of the ferrets developed neurological signs. Non-regenerative anaemia and high serum concentrations of alpha- and beta-globulins were the most common laboratory findings. Most of the animals died or were euthanased because of respiratory complications. Postmortem there were no signs of lung collapse. Distemper was diagnosed by direct immunofluorescence of conjunctival swabs or pcr of several organs, and histology revealed the characteristic eosinophilic intracytoplasmic and intranuclear inclusion bodies of canine distemper virus in several organs. The minimum incubation periods calculated for six of the ferrets were 11 to 56 days, and in 13 of the ferrets the signs of disease lasted 14 to 34 days. Inclusion bodies compatible with infection by herpesvirus were found in the lungs of one of the ferrets.

  3. Vaccines for Canine Leishmaniasis

    PubMed Central

    Palatnik-de-Sousa, Clarisa B.

    2012-01-01

    Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL) is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global warming, coinfection with immunosuppressive diseases, and poverty. The disease is an anthroponosis in India and Central Africa and a canid zoonosis (ZVL) in the Americas, the Middle East, Central Asia, China, and the Mediterranean. The ZVL epidemic has been controlled by one or more measures including the culling of infected dogs, treatment of human cases, and insecticidal treatment of homes and dogs. However, the use of vaccines is considered the most cost–effective control tool for human and canine disease. Since the severity of the disease is related to the generation of T-cell immunosuppression, effective vaccines should be capable of sustaining or enhancing the T-cell immunity. In this review we summarize the clinical and parasitological characteristics of ZVL with special focus on the cellular and humoral canine immune response and review state-of-the-art vaccine development against human and canine VL. Experimental vaccination against leishmaniasis has evolved from the practice of leishmanization with living parasites to vaccination with crude lysates, native parasite extracts to recombinant and DNA vaccination. Although more than 30 defined vaccines have been studied in laboratory models no human formulation has been licensed so far; however three second-generation canine vaccines have already been registered. As expected for a zoonotic disease, the recent preventive vaccination of dogs in Brazil has led to a reduction in the incidence of canine and human disease. The recent identification of several Leishmania proteins with T-cell epitopes anticipates development of a multiprotein vaccine that will be capable of protecting both humans and dogs against VL. PMID:22566950

  4. Canine distemper virus associated proliferation of canine footpad keratinocytes in vitro.

    PubMed

    Engelhardt, P; Wyder, M; Zurbriggen, A; Gröne, A

    2005-04-25

    Infection of canine footpads with canine distemper virus (CDV) can result in so-called hard pad disease characterized by footpad epidermal proliferation and hyperkeratosis. Cultured canine footpad keratinocytes (CFK) were inoculated with a virulent canine distemper virus strain (A75/17-CDV) to study the effects of CDV-infection on keratinocyte proliferation. Infection was analyzed by immunohistochemistry and in situ hybridization for CDV nucleoprotein (N-protein) antigen and mRNA. CDV caused a persistent, non-cytocidal infection with spread from single cells to infection of the confluent cell layer 7 days post infection (p.i.). Absolute cell numbers were significantly higher in infected cultures compared to control cultures from day 4 until day 6 p.i. Infected cultures contained significantly more total DNA on day 5 p.i. compared to controls. Immunohistochemical investigation of proliferation markers Ki67 and BrdU demonstrated a nearly two-fold increase in numbers of positive cells on day 5 p.i. compared to controls. These findings demonstrate that canine distemper virus infection of canine footpad keratinocytes in vitro was associated with proliferation.

  5. Advances in canine distemper virus pathogenesis research: a wildlife perspective.

    PubMed

    Loots, Angelika K; Mitchell, Emily; Dalton, Desiré L; Kotzé, Antoinette; Venter, Estelle H

    2017-03-01

    Canine distemper virus (CDV) has emerged as a significant disease of wildlife, which is highly contagious and readily transmitted between susceptible hosts. Initially described as an infectious disease of domestic dogs, it is now recognized as a global multi-host pathogen, infecting and causing mass mortalities in a wide range of carnivore species. The last decade has seen the effect of numerous CDV outbreaks in various wildlife populations. Prevention of CDV requires a clear understanding of the potential hosts in danger of infection as well as the dynamic pathways CDV uses to gain entry to its host cells and its ability to initiate viral shedding and disease transmission. We review recent research conducted on CDV infections in wildlife, including the latest findings on the causes of host specificity and cellular receptors involved in distemper pathogenesis.

  6. Characteristics of a Canine Distemper Virus Outbreak in Dichato, Chile Following the February 2010 Earthquake

    PubMed Central

    Garde, Elena; Pérez, Guillermo; Acosta-Jamett, Gerardo; Bronsvoort, Barend Mark

    2013-01-01

    Simple Summary A disease outbreak in domestic dogs was reported by a coastal Chilean community following the February 2010 earthquake and tsunami. Using clinical exams and diagnostic testing, canine distemper virus was confirmed. Most dogs seen had never been vaccinated, and the majority of those with positive results were recorded in dogs less than two years of age. There were no facilities to contain or treat dogs locally, and no plan to shelter free-roaming dogs. This observational study demonstrates the great need for disaster preparedness planning in developing countries that includes companion animals. Abstract Following the earthquake and tsunami disaster in Chile in February 2010, residents of Dichato reported high morbidity and mortality in dogs, descriptions of which resembled canine distemper virus (CDV). To assess the situation, free vaccine clinics were offered in April and May. Owner information, dog history and signalment were gathered; dogs received physical examinations and vaccines protecting against CDV, and other common canine pathogens. Blood was collected to screen for IgM antibodies to CDV. In total, 208 dogs received physical exams and vaccines were given to 177. IgM antibody titres to CDV were obtained for 104 dogs. Fifty-four dogs (51.9%) tested positive for CDV at the cut off titre of >1:50, but a total of 91.4% of dogs had a detectable titre >1:10. Most of the positive test results were in dogs less than 2 years of age; 33.5% had been previously vaccinated against CDV, and owners of 84 dogs (42.2%) reported clinical signs characteristic of CDV in their dogs following the disaster. The presence of endemic diseases in dog populations together with poor pre-disaster free-roaming dog management results in a potential for widespread negative effects following disasters. Creation of preparedness plans that include animal welfare, disease prevention and mitigation should be developed. PMID:26479537

  7. Vimentin-positive astrocytes in canine distemper: a target for canine distemper virus especially in chronic demyelinating lesions?

    PubMed

    Seehusen, Frauke; Orlando, Enzo A; Wewetzer, Konstantin; Baumgärtner, Wolfgang

    2007-12-01

    In canine distemper demyelinating leukoencephalitis (DL), caused by canine distemper virus (CDV), astrocytes represent the main virus target. In these cells, glial fibrillary acidic protein (GFAP) is the main intermediate filament, whereas vimentin occurs early in the astrocytic lineage and is replaced gradually by GFAP. To further characterize the role of astrocytic infection in dogs with DL, an animal model for multiple sclerosis, formalin-fixed paraffin-embedded cerebella were investigated immunohistochemically and by immunofluorescence. The expression and morphological alterations of these intermediate filaments were also determined by immunofluorescence studies of CDV-infected canine mixed brain cell cultures. In acute distemper lesions, the astrocytic response was mainly composed of GFAP- and CDV-positive cells. In contrast, vimentin-positive astrocyte-like cells were present in advanced lesions, which represented the main cell type harboring the pathogen, indicating a change in cell tropism and/or susceptibility of glial cells during lesion progression in CDV encephalomyelitis. Canine cell cultures were composed of GFAP-positive astrocytes, vimentin-positive cells and other glial cells. Following infection with the CDV-R252 strain, GFAP-positive astrocytes, especially multinucleated syncytial giant cells, displayed a disrupted cytoskeleton, whereas vimentin-positive cells though more frequently infected did not show any alteration in the filament network. This indicates increased vulnerability of mature GFAP-positive astrocytes compared to immature, vimentin-positive astrocytes. The latter, however, exhibited increased susceptibility to CDV. To conclude, the present findings indicate a change in cell tropism of CDV and/or the occurrence of less differentiated astrocytes representing a permanent source for virus infection and spread in advanced lesions of DL.

  8. Occurrence of filaria in domestic dogs of Samburu pastoralists in Northern Kenya and its associations with canine distemper.

    PubMed

    Albrechtová, Kateřina; Sedlák, Kamil; Petrželková, Klára J; Hlaváč, Jan; Mihalca, Andrei D; Lesingirian, Alison; Kanyari, Paul W N; Modrý, David

    2011-12-15

    Samples of blood (serum, smears and blood preserved with ethanol) were collected from dogs during a vaccination campaign in northern Kenya in the years 2006 and 2007. Blood was screened for filarial parasites using molecular and microscopy methods and sera were tested for antibodies against canine distemper virus (CDV). Parasitological examination revealed the presence of two species of canine filariae: Acanthocheilonema dracunculoides and A. reconditum. The DNA from the former species was detected in 58% dogs sampled in 2006 and 36% dogs sampled in 2007, whereas the latter was found only in 4.2% samples collected in 2007. Microfilariae were found in 33.8% blood smears collected in 2006 and 10.6% blood smears collected in 2007. The seroprevalence of CDV was 33.4% in 2006 and 11.2% in 2007. The effect of sex, age and CDV-seropositivity/seronegativity on the occurrence of A. dracunculoides was evaluated. Infection by A. dracunculoides was more common in males and in dogs with a positive antibody titer for canine distemper, but evenly distributed among different age groups. The difference in the prevalence of A. dracunculoides in two isolated mountain ranges was not statistically significant. Methodologies available for detection and determination of canine filariae are compared, underlining methodical pitfalls arising through the determination of less common filarial species. The role of single epidemiological factors and possible association between canine distemper and filariasis are discussed.

  9. Interstitial pneumonia in neonatal canine pups with evidence of canine distemper virus infection.

    PubMed

    Pandher, Karamjeet; Podell, Brendan; Gould, Daniel H; Johnson, Bill J; Thompson, Sheri

    2006-03-01

    Four dead canine pups (5-12 days old) from 3 litters in Douglas County of north central Colorado were submitted to the Colorado State University Diagnostic Laboratory for necropsy. Pups were originally presented to the referring clinics for respiratory tract illness, with or without diarrhea. At necropsy, the lungs from all pups had similar lesions, including random foci of hemorrhage and failure to collapse on opening of the thoracic cavity. The lungs were histologically characterized by subacute interstitial pneumonia, with alveolar septa expanded by a histiocyte-rich infiltrate with a few lymphocytes and neutrophils. The alveolar spaces were filled with moderate amounts of proteinaceous fluid, foamy macrophages, and a few neutrophils. Lungs from 3 of the 4 pups were test positive for canine distemper virus (CDV) by use of reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Immunohistochemically stained lungs, including those from the pup that were CDV negative, by use of RT-PCR analysis, were test positive for CDV antigen in bronchial and bronchiolar epithelial cells and in a few alveolar macrophages. Central nervous system lesions were not observed in any of the 4 pups. These cases represent an unusual presentation of canine distemper in neonatal pups marked by respiratory tract lesions without central nervous system involvement. Canine distemper should be considered in the differential diagnosis of neonatal canine respiratory tract illness.

  10. Occurrence of different Canine distemper virus lineages in Italian dogs.

    PubMed

    Balboni, Andrea; De Lorenzo Dandola, Giorgia; Scagliarini, Alessandra; Prosperi, Santino; Battilani, Mara

    2014-01-01

    This study describes the sequence analysis of the H gene of 7 Canine distemper virus (CDV) strains identified in dogs in Italy between years 2002-2012. The phylogenetic analysis showed that the CDV strains belonged to 2 clusters: 6 viruses were identified as Arctic-like lineage and 1 as Europe 1 lineage. These data show a considerable prevalence of Arctic-like-CDVs in the analysed dogs. The dogs and the 3 viruses more recently identified showed 4 distinctive amino acid mutations compared to all other Arctic CDVs.

  11. Evidence of two co-circulating genetic lineages of canine distemper virus in South America.

    PubMed

    Panzera, Yanina; Calderón, Marina Gallo; Sarute, Nicolás; Guasco, Soledad; Cardeillac, Arianne; Bonilla, Braulio; Hernández, Martín; Francia, Lourdes; Bedó, Gabriela; La Torre, José; Pérez, Ruben

    2012-01-01

    Canine distemper virus (CDV) is the etiological agent of a multisystemic infection that affects different species of carnivores and is responsible for one of the main diseases suffered by dogs. Recent data have shown a worldwide increase in the incidence of the disease, including in vaccinated dog populations, which necessitates the analysis of circulating strains. The hemagglutinin (H) gene, which encodes the major antigenic viral protein, has been widely used to determine the degree of genetic variability and to associate CDVs in different worldwide circulating lineages. Here, we obtained the sequence of the first full-length H gene of field South American CDV strains and compared it with sequences of worldwide circulating field strains and vaccine viruses. In South America, we detect two co-circulating lineages with different prevalences: the Europe 1 lineage and a new South America 2 lineage. The Europe 1 lineage was the most prevalent in South America, and we suggest renaming it the Europe 1/South America 1 lineage. The South America 2 lineage was found only in Argentina and appears related to wild CDV strains. All South American CDV strains showed high amino-acid divergence from vaccine strains. This genetic variability may be a possible factor leading to the resurgence of distemper cases in vaccinated dog populations.

  12. Aspects of canine distemper virus and measles virus encephalomyelitis.

    PubMed

    Summers, B A; Appel, M J

    1994-12-01

    Canine distemper (CD) is a frequently fatal, systemic morbillivirus infection in the dog and other carnivores: encephalomyelitis is the common cause of death. Susceptibility to canine distemper virus (CDV) is now recognized in a wide range of non-domestic animals, most recently in captive lions, tigers and leopards. Furthermore, closely related viruses have produced CD-like diseases in marine mammals. CDV induces an inclusion-body encephalomyelitis in the dog and demyelination is often a conspicuous feature. Myelin injury is associated with the presence of virus but the mechanism of demyelination remains incompletely understood. Oligodendrocyte infection may be defective, as has been shown in vitro. CDV and measles virus (MV) produce similar systemic disorders in their respective hosts but differ markedly in the frequency of central nervous system (CNS) involvement, and in the pathogenesis of the more common neurological sequelae. Both CDV and MV have been considered as multiple sclerosis agents, and the association of CDV with other human disease has been suggested.

  13. Demyelination in canine distemper virus infection: a review.

    PubMed

    Vandevelde, Marc; Zurbriggen, Andreas

    2005-01-01

    Canine distemper virus (CDV) causes severe immunosuppression and neurological disease in dogs, associated with demyelination, and is a model for multiple sclerosis in man. In the early stage of the infection, demyelination is associated with viral replication in the white matter. In acute demyelinating lesions there is massive down-regulation of myelin transcription and metabolic impairment of the myelin-producing cells, but there is no evidence that these cells are undergoing apoptosis or necrosis. Oligodendroglial change is related to restricted infection of these cells (transcription but no translation) and marked activation of microglial cells in acute lesions. Concomitant with immunological recovery during the further course of the disease, inflammation occurs in the demyelinating plaques with progression of the lesions in some animals. A series of experiments in vitro suggests that chronic inflammatory demyelination is due to a bystander mechanism resulting from interactions between macrophages and antiviral antibodies. Autoimmune reactions are also observed, but do not correlate with the course of the disease. The progressive or relapsing course of the disease is associated with viral persistence in the nervous system. Persistence of CDV in the brain appears to be favored by non-cytolytic selective spread of the virus and restricted infection, in this way escaping immune surveillance in the CNS. The CDV Fusion protein appears to play an important role in CDV persistence. Similarities between canine distemper and rodent models of virus-induced demyelination are discussed.

  14. Immunohistochemical demonstration of the putative canine distemper virus receptor CD150 in dogs with and without distemper.

    PubMed

    Wenzlow, N; Plattet, P; Wittek, R; Zurbriggen, A; Gröne, A

    2007-11-01

    Signaling lymphocyte activation molecule (SLAM) or CD150 can function as a receptor for the canine distemper virus (CDV) in vitro. The expression of SLAM was studied using immunohistochemistry in order to evaluate the presence and distribution of the receptor in dogs in vivo. Additionally, receptor expression was assessed after experimental infection of dogs with CDV. In 7 control dogs without distemper virus, the receptor was found in various tissues, mostly on cells morphologically identified as lymphocytes and macrophages. In 7 dogs with early distemper lesions characterized by presence of the virus, higher numbers of SLAM-expressing cells were found in multiple tissues recognized as targets of CDV compared with those in control dogs. These findings suggest that SLAM, a putative distemper receptor, is expressed in dogs in vivo. Additionally, virus infection is associated with up-regulation of SLAM, potentially causing an amplification of virus in the host.

  15. Distribution of inclusion bodies in tissues from 100 dogs infected with canine distemper virus.

    PubMed

    Kubo, Takuya; Kagawa, Yumiko; Taniyama, Hiroyuki; Hasegawa, Atsuhiko

    2007-05-01

    One hundred dogs that were positive for canine distemper virus antigen and inclusion bodies in the tonsils were examined for the distribution of inclusion bodies in various tissues. Inclusion bodies were found in the lungs (70 dogs), brains (20 dogs), urinary bladders (73 dogs), stomachs (78 dogs), spleens (77 dogs), and lymph nodes (81 dogs) of the dogs. Based on these results, the tonsils may be the most suitable tissue for detection of inclusion bodies in canine distemper.

  16. Characterization of a novel Canine distemper virus causing disease in wildlife.

    PubMed

    Pope, Jenny P; Miller, Debra L; Riley, Matthew C; Anis, Eman; Wilkes, Rebecca P

    2016-09-01

    Canine distemper virus (CDV) is a common cause of a multisystemic disease in both domestic dogs and wildlife species, including raccoons and foxes. Outbreaks of CDV in domestic dogs in eastern Tennessee have occurred since 2012, and it was determined that these outbreaks resulted from a novel genotype of CDV. We hypothesized that this virus is also infecting area wildlife and may be a source of the virus for these outbreaks in dogs. From 2013 to 2014, autopsies were performed and tissues collected from raccoons (Procyon lotor; n = 50) and gray foxes (Urocyon cinereoargenteus; n = 8) for CDV testing. A real-time reverse transcription PCR was used to document the presence of CDV in tissue samples, and a portion of the virus was subsequently sequenced for phylogenetic analysis. A high percentage of wildlife, both with (86%) and without (55%) clinical signs, tested positive for CDV, with the majority (77%) testing positive for the novel genotype. Microscopic findings, including syncytia in the lungs and viral inclusion bodies in urothelium, astrocytes, neurons, and bronchiolar epithelium, were also consistent with canine distemper. Minimal inflammation in the central nervous system of affected animals was indicative of the acute neurologic form of the disease. Pneumonia and parasitism were also commonly found in CDV-infected animals. Based on these results, CDV appears to be prevalent in eastern Tennessee wildlife. Subclinical or clinically recovered shedders are a potential source of this novel genotype for domestic dogs, and this genotype is genetically distinct from vaccine strains.

  17. Canine distemper virus induces apoptosis through caspase-3 and -8 activation in vero cells.

    PubMed

    Kajita, M; Katayama, H; Murata, T; Kai, C; Hori, M; Ozaki, H

    2006-08-01

    We investigated the signal-transduction pathway of canine distemper virus-Onderstepoort (CDV-Ond) vaccine strain-mediated apoptosis in Vero cells. Canine distemper virus-Onderstepoort at a multiplicity of infection (MOI) of 0.1 induced DNA fragmentation 48 h after infection. Immunofluorescence staining revealed that 57% +/- 4% of the CDV-N-protein-positive cells were terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive, and all TUNEL-positive cells were CDV-N-protein-positive, indicating that CDV-Ond induced apoptosis only in the infected cells. We also found that CDV-Ond infection induced activation of caspase-3 and caspase-8. In the semi-quantitative reverse transcription-polymerase chain reaction assay for apoptosis-related genes, the expression of mRNA of the death receptor, Fas, was also increased in CDV-Ond-infected cells. In contrast, the expressions of Bcl-2 and Bax, regulators for intrinsic apoptotic signaling through the mitochondria, did not change. These results suggest that CDV-Ond induced apoptosis by activating caspase-3, possibly through caspase-8 signaling rather than through p53/Bax-mediated, mitochondrial signaling in the infected cells.

  18. A recombinant canine distemper virus expressing a modified rabies virus glycoprotein induces immune responses in mice.

    PubMed

    Li, Zhili; Wang, Jigui; Yuan, Daoli; Wang, Shuang; Sun, Jiazeng; Yi, Bao; Hou, Qiang; Mao, Yaping; Liu, Weiquan

    2015-06-01

    Canine distemper virus (CDV) and rabies virus (RV) are two important pathogens of the dog. CDV, a member of the morbillivirus genus, has shown promise as an expression vector. The glycoprotein from RV is a main contributor to protective immunity and capable of eliciting the production of virus-neutralizing antibodies. In this study, we recovered an attenuated strain of canine distemper virus and constructed a recombinant virus, rCDV-RV-G, expressing a modified (R333Q) rabies virus glycoprotein (RV-G) of RV Flury strain LEP. RV-G expression by the recombinant viruses was confirmed. Furthermore, G was proved to be incorporated into the surface of CDV particles. While replication of the recombinant virus was slightly reduced compared with the parental CDV, it stably expressed the RV-G over ten serial passages. Inoculation of mice induced specific neutralizing antibodies against both RV-G and CDV. Therefore, the rCDV-RV-G has the potential as a vaccine that may be used to control rabies virus infection in dogs and other animals.

  19. Canine distemper virus in a crab-eating fox (Cerdocyon thous) in Brazil: case report and phylogenetic analyses.

    PubMed

    Megid, Jane; de Souza, Vanessa Aparecida Feijó; Teixeira, Carlos Roberto; Cortez, Adriana; Amorin, Renée Laufer; Heinemman, Marcos Bryan; Cagnini, Didier Quevedo; Richtzenhain, Leonardo José

    2009-04-01

    Although canine distemper is enzootic worldwide and has a wide host range, there are no reports of canine distemper virus in crab-eating foxes (Cerdocyon thous) that provide information on virus phylogeny and histopathologic lesions. The objective of this study is report and describe canine distemper in a crab-eating fox (C. thous), with a focus on the phylogeny of the virus strain and the histopathologic lesions in the animal.

  20. Recombinant rabies virus expressing the H protein of canine distemper virus protects dogs from the lethal distemper challenge.

    PubMed

    Wang, Feng-Xue; Zhang, Shu-Qin; Zhu, Hong-Wei; Yang, Yong; Sun, Na; Tan, Bin; Li, Zhen-Guang; Cheng, Shi-Peng; Fu, Zhen F; Wen, Yong-Jun

    2014-12-05

    The rabies virus (RV) vector LBNSE expressing foreign antigens have shown considerable promise as vaccines against viral and bacteria diseases, which is effective and safe. We produced a new RV-based vaccine vehicle expressing 1.824 kb hemagglutinin (H) gene of the canine distemper virus (CDV) by reverse genetics technology. The recombinant virus LBNSE-CDV-H retained growth properties similar to those of vector LBNSE both in BSR and mNA cell culture. The H gene of CDV was expressed and detected by immunostaining. To compare the immunogenicity of LBNSE-CDV-H, dogs were immunized with each of these recombinant viruses by intramuscular (i.m.). The dogs were bled at third weeks after the immunization for the measurement of virus neutralizing antibody (VNA) and then challenged with virulent virus (ZJ 7) at fourth weeks. The parent virus (LBNSE) without expression of any foreign molecules was included for comparison. Dogs inoculated with LBNSE-CDV-H showed no any signs of disease and exhibited seroconversion against both RV and CDV H protein. The LBNSE-CDV-H did not cause disease in dogs and conferred protection from challenge with a lethal wild type CDV strain, demonstrating its potential value for wildlife conservation efforts. Together, these studies suggest that recombinant RV expressing H protein from CDV stimulated high levels of adaptive immune responses (VNA), and protected all dogs challenge infection.

  1. Molecular identification of a recent type of canine distemper virus in Japan by restriction fragment length polymorphism.

    PubMed

    Ohashi, K; Iwatsuki, K; Nakamura, K; Mikami, T; Kai, C

    1998-11-01

    Restriction fragment length polymorphism analysis was used to differentiate recent field viruses of canine distemper virus (CDU) from vaccine strains. Virus genomes were amplified by using reverse transcriptase-polymerase chain reaction in part of the haemagglutinin gene. After digestion with EcoRV, the PCR products of recent field isolates were cut into two fragments that differ from the uncut form of old strains including all of vaccine strains. This method could be applied to fresh or stored brains, spleens and peripheral blood mononuclear cells of infected dogs. This molecular approach is useful for determining the causative agent of postvaccinated CDV infection.

  2. Detection of canine distemper virus by reverse transcriptase-polymerase chain reaction in the urine of dogs with clinical signs of distemper encephalitis.

    PubMed

    Saito, T B; Alfieri, A A; Wosiacki, S R; Negrão, F J; Morais, H S A; Alfieri, A F

    2006-02-01

    In a prospective study we evaluated the use of the reverse transcriptase-polymerase chain reaction (RT-PCR) in urine samples to diagnose canine distemper virus in dogs with progressive neurological disease. A fragment of the nucleoprotein gene of canine distemper virus was amplified from the urine of 22 distemper dogs. The body fluids and leukocytes of 12 asymptomatic dogs were RT-PCR negative. RT-PCR of urine samples was more sensitive than serum and leukocytes and at least as sensitive as cerebrospinal fluid to screen for distemper in dogs with neurological signs and extraneural systemic signs.

  3. Microglial cell activation in demyelinating canine distemper lesions.

    PubMed

    Stein, Veronika M; Czub, Markus; Schreiner, Nicole; Moore, Peter F; Vandevelde, Marc; Zurbriggen, Andreas; Tipold, Andrea

    2004-08-01

    Microglia cells are the principal immune effector elements of the brain responding to any pathological event. To elucidate the possible role of microglia in initial non-inflammatory demyelination in canine distemper virus (CDV) infection, microglia from experimentally CDV infected dogs were isolated ex vivo by density gradient centrifugation and characterized immunophenotypically and functionally using flow cytometry. Results from dogs with demyelinating lesions were compared to results from recovered dogs and two healthy controls. CDV antigen could be detected in microglia of dogs with histopathologically confirmed demyelination. Microglia of these dogs showed marked upregulation of the surface molecules CD18, CD11b, CD11c, CD1c, MHC class I and MHC class II and a tendency for increased expression intensity of ICAM-1 (CD54), B7-1 (CD80), B7-2 (CD86), whereas no increased expression was found for CD44 and CD45. Functionally, microglia exhibited distinctly enhanced phagocytosis and generation of reactive oxygen species (ROS). It was concluded that in CDV infection, there is a clear association between microglial activation and demyelination. This strongly suggests that microglia contribute to acute myelin destruction in distemper.

  4. Canine distemper infections, with special reference to South Africa, with a review of the literature.

    PubMed

    Leisewitz, A L; Carter, A; van Vuuren, M; van Blerk, L

    2001-09-01

    Canine distemper virus is a member of the genus Morbillivirus of the family Paramyxoviridae that causes severe disease in dogs and a range of wild mammals. The clinical signs relate essentially to the respiratory, gastrointestinal and central nervous systems. In South Africa, infection with Ehrlichia canis and canine parvovirus may present similarly Many dogs will initially present with a wide range of central nervous system signs without any history of systemic disease. A recent South African study evaluating ante mortem diagnosis highlighted the importance of recognising clinical signs, cerebrospinal fluid IgG titres, serum IgM titres and immunocytochemistry of epithelial tissue. A 2-year retrospective evaluation of cerebrospinal fluid samples collected from dogs presented to the Onderstepoort Veterinary Academic Hospital indicates that distemper infection is common, and this disease should routinely be suspected in cases of diverse neurological disease in dogs. The South African dog population is specifically at high risk for the disease because of the large pool of unvaccinated, reproductively-active dogs that expose the wildlife resources of the country to risk of fatal disease. Outbreaks of disease in dogs continue to occur in developed and developing communities in both vaccinated and unvaccinated dogs worldwide, and have also been described in a wide range of free-ranging wildlife, including seals, dolphins and lions, and in endangered zoo animals. Modified live virus vaccines have contributed markedly to disease control in the dog population but have caused mortality in some wild carnivores. New recombinant vaccines are being developed that will be safe in wild animals. The pathogenesis of CNS demyelination has been compared to various important demyelinating diseases in humans and, amongst other things, relates to down-regulation of the oligodendrocyte gene coding for myelin synthesis and non-immunocyte CNS cell expression of type II major

  5. Genetic characterization of canine distemper virus in Serengeti carnivores.

    PubMed

    Carpenter, M A; Appel, M J; Roelke-Parker, M E; Munson, L; Hofer, H; East, M; O'Brien, S J

    1998-10-23

    The lion (Panthera leo) population in the Serengeti ecosystem was recently afflicted by a fatal epidemic involving neurological disease, encephalitis and pneumonia. The cause was identified as canine distemper virus (CDV). Several other species in the Serengeti were also affected. This report presents CDV H and P gene sequences isolated from Serengeti lions (Panthera leo), spotted hyenas (Crocuta crocuta), bat-eared fox (Otocyon megalotis) and domestic dog (Canis familiaris). Sequence analyses demonstrated that the four Serengeti species carry closely related CDV isolates which are genetically distinct from other CDV isolates from various species and locations. The results are consistent with the conclusions that: (1) a particularly virulent strain of CDV emerged among Serengeti carnivores within the last few years; (2) that strain has recognizable shared-derived (synapomorphic) genetic differences in both H and P genes when compared to CDV from other parts of the world; and (3) that the CDV strain has frequently crossed host species among Serengeti carnivores.

  6. Canine distemper virus infection in fennec fox (Vulpes zerda).

    PubMed

    Woo, Gye-Hyeong; Jho, Yeon-Sook; Bak, Eun-Jung

    2010-08-01

    Fifteen 8-month-old fennec foxes imported from Sudan showed fever, mucopurulent ocular discharge, diarrhea, severe emaciation, seizures, and generalized ataxia, and died. Three of the 15 animals were presented for diagnostic investigation. Severe dehydration, brain congestion, and gastric ulcers were observed in all animals. In one animal, the lungs had failed to collapse and were multifocally dark red in appearance. Histopathologically, there were lymphohistiocytic meningoencephalitis with malacia, mild interstitial pneumonia, lymphoid depletion of lymphoid tissues and organs, and intestinal villous atrophy with intralesional coccidia. There were many intracytoplasmic and/or intranuclear inclusion bodies in the epithelial cells of the medullary velum, lungs, liver, kidneys, trachea, pancreas, stomach, gall bladder, urinary bladder, and ureters, and in macrophages of malacia foci and lymphocytes and macrophages of lymphoid organs. Additionally, intestinal coccidia were confirmed to be Isospora species by a fecal test. To our knowledge, this is the first report of canine distemper with intestinal coccidiosis in fennec fox.

  7. Pathogenesis and immunopathology of systemic and nervous canine distemper.

    PubMed

    Beineke, A; Puff, C; Seehusen, F; Baumgärtner, W

    2009-01-15

    Canine distemper is a worldwide occurring infectious disease of dogs, caused by a morbillivirus, closely related to measles and rinderpest virus. The natural host range comprises predominantly carnivores. Canine distemper virus (CDV), an enveloped, negative-sense RNA virus, infects different cell types, including epithelial, mesenchymal, neuroendocrine and hematopoietic cells of various organs and tissues. CDV infection of dogs is characterized by a systemic and/or nervous clinical course and viral persistence in selected organs including the central nervous system (CNS) and lymphoid tissue. Main manifestations include respiratory and gastrointestinal signs, immunosuppression and demyelinating leukoencephalomyelitis (DL). Impaired immune function, associated with depletion of lymphoid organs, consists of a viremia-associated loss of lymphocytes, especially of CD4+ T cells, due to lymphoid cell apoptosis in the early phase. After clearance of the virus from the peripheral blood an assumed diminished antigen presentation and altered lymphocyte maturation cause an ongoing immunosuppression despite repopulation of lymphoid organs. The early phase of DL is a sequel of a direct virus-mediated damage and infiltrating CD8+ cytotoxic T cells associated with an up-regulation of pro-inflammatory cytokines such as interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-alpha and IL-12 and a lacking response of immunomodulatory cytokines such as IL-10 and transforming growth factor (TGF)-beta. A CD4+-mediated delayed type hypersensitivity and cytotoxic CD8+ T cells contribute to myelin loss in the chronic phase. Additionally, up-regulation of interferon-gamma and IL-1 may occur in advanced lesions. Moreover, an altered balance between matrix metalloproteinases and their inhibitors seems to play a pivotal role for the pathogenesis of DL. Summarized, DL represents a biphasic disease process consisting of an initial direct virus-mediated process and immune-mediated plaque

  8. Histopathology and immunohistochemistry of canine distemper virus-induced footpad hyperkeratosis (hard Pad disease) in dogs with natural canine distemper.

    PubMed

    Koutinas, A F; Baumgärtner, W; Tontis, D; Polizopoulou, Z; Saridomichelakis, M N; Lekkas, S

    2004-01-01

    Hard pad disease represents an uncommon manifestation of canine distemper virus (CDV) infection with a still uncertain pathogenesis. To study the pathogenesis of this uncommon, virally induced cutaneous lesion, the footpads of 19 dogs with naturally occurring distemper were investigated for histologic changes and distribution pattern of CDV antigen. All dogs displayed clinical signs of distemper, which had lasted from 10 to 75 days. Overt digital hyperkeratosis was observed in 12 animals (group A), whereas the footpads of the remaining seven dogs appeared normal macroscopically (group B). Orthokeratotic hyperkeratosis (12/12; 100%), irregular acanthosis (11/12; 92%), thickened rete ridges (10/12; 83%), and mild mononuclear perivascular (10/ 12; 83%) and periadnexal (7/12; 58%) dermatitis were the most common findings in dogs with hard pad disease. Surprisingly, orthokeratotic hyperkeratosis (5/7; 71%), irregular acanthosis (5/7; 71%), and thickened rete ridges (4/7; 57%) were also seen in the dogs without clinical evidence of digital hyperkeratosis. CDV-specific inclusion bodies and ballooning degeneration were not observed in the footpad epidermis of the 19 dogs. Immunohis-tochemistry revealed that CDV antigen was most frequently found in the stratum spinosum and granulosum and in the epithelial cells of the eccrine sweat glands and only rarely in the basal layer. Fibroblasts, pericytes, endothelial cells, and hair follicles were also positive in some animals. Despite the obvious difference regarding the macroscopic picture, the microscopic changes were less prominent between the animal groups. The selective infection of keratinocytes in the stratum spinosum might be the key event for the development of hard pad disease in the dog.

  9. Detection of canine distemper virus in dogs by real-time RT-PCR.

    PubMed

    Elia, Gabriella; Decaro, Nicola; Martella, Vito; Cirone, Francesco; Lucente, Maria Stella; Lorusso, Eleonora; Di Trani, Livia; Buonavoglia, Canio

    2006-09-01

    Canine distemper virus is the etiological agent of a severe disease in dogs and many other carnivores. Clinical diagnosis of canine distemper is difficult due to the broad spectrum of signs that may be confounded with other respiratory and enteric diseases of dogs. Accordingly, a laboratory confirmation is required for suspected cases. In this study a real-time RT-PCR assay was developed for detection and quantitation of canine distemper virus. The assay exhibited high specificity as all the negative controls (no-template-controls and samples from healthy sero-negative dogs) and other canine pathogens were not misdetected. Up to 1 x 10(2) copies of RNA were detected by the TaqMan assay, thus revealing a high sensitivity. Quantitative TaqMan was validated on clinical samples, including various tissues and organs collected from dogs naturally infected by canine distemper virus. Urines, tonsil, conjunctival swabs and whole blood were found to contain high virus loads and therefore proved to be suitable targets for detection of canine distemper virus RNA.

  10. Serologic investigations of canine parvovirus and canine distemper in relation to wolf (Canis lupus) pup mortalities.

    PubMed

    Johnson, M R; Boyd, D K; Pletscher, D H

    1994-04-01

    Twenty-one serum samples from 18 wolves (Canis lupus) were collected from 1985 to 1990 from northwestern Montana (USA) and southeastern British Columbia, Canada, and evaluated for antibodies to canine parvovirus (CPV), canine distemper (CD), infectious canine hepatitis, and Lyme disease; we found prevalences of 13 (65%) of 19, five (29%) of 17, seven (36%) of 19, and 0 of 20 wolves for these diseases, respectively. Pups died or disappeared in three of the eight packs studied. In these three packs, adult pack members had CPV titers > or = 1,600 or CD titers > or = 1,250. In packs that successfully raised pups, CPV and CD titers were low. We propose that CPV or CD may have caused some pup mortalities.

  11. Morbillivirus Experimental Animal Models: Measles Virus Pathogenesis Insights from Canine Distemper Virus.

    PubMed

    da Fontoura Budaszewski, Renata; von Messling, Veronika

    2016-10-11

    Morbilliviruses share considerable structural and functional similarities. Even though disease severity varies among the respective host species, the underlying pathogenesis and the clinical signs are comparable. Thus, insights gained with one morbillivirus often apply to the other members of the genus. Since the Canine distemper virus (CDV) causes severe and often lethal disease in dogs and ferrets, it is an attractive model to characterize morbillivirus pathogenesis mechanisms and to evaluate the efficacy of new prophylactic and therapeutic approaches. This review compares the cellular tropism, pathogenesis, mechanisms of persistence and immunosuppression of the Measles virus (MeV) and CDV. It then summarizes the contributions made by studies on the CDV in dogs and ferrets to our understanding of MeV pathogenesis and to vaccine and drugs development.

  12. Canine distemper virus utilizes different receptors to infect chicken embryo fibroblasts and vero cells.

    PubMed

    Chen, Jun; Liang, Xiu; Chen, Pei-fu

    2011-04-01

    Inducing animal viruses to adapt to chicken embryos or chicken embryo fibroblasts (CEF) is a common method to develop attenuated live vaccines with full security. Canine distemper virus (CDV) also does this, but the mechanisms and particular receptors remain unclear. Virus overlay protein blot assays were carried out on CEF membrane proteins, which were extracted respectively with a Mem-PER™ kit, a radioimmunoprecipitation assay buffer or a modified co-immunoprecipitation method, and revealed a common 57 kDa positive band that differed from the 42-kDa positive band in Vero cells and also from those receptors reported in lymphocytes and 293 cells, indicating a receptor diversity of CDV and the possibility of the 57-kDa protein acting as a receptor that is involved in adaptive infection of CDV Kunming strain to CEF.

  13. Phylogenetic analysis of canine distemper virus in domestic dogs in Nanjing, China.

    PubMed

    Bi, Zhenwei; Wang, Yongshan; Wang, Xiaoli; Xia, Xingxia

    2015-02-01

    Canine distemper virus (CDV) infects a broad range of carnivores, including wild and domestic Canidae. The hemagglutinin gene, which encodes the attachment protein that determines viral tropism, has been widely used to determine the relationship between CDV strains of different lineages circulating worldwide. We determined the full-length H gene sequences of seven CDV field strains detected in domestic dogs in Nanjing, China. A phylogenetic analysis of the H gene sequences of CDV strains from different geographic regions and vaccine strains was performed. Four of the seven CDV strains were grouped in the same cluster of the Asia-1 lineage to which the vast majority of Chinese CDV strains belong, whereas the other three were clustered within the Asia-4 lineage, which has never been detected in China. This represents the first record of detection of strains of the Asia-4 lineage in China since this lineage was reported in Thailand in 2013.

  14. Morbillivirus Experimental Animal Models: Measles Virus Pathogenesis Insights from Canine Distemper Virus

    PubMed Central

    da Fontoura Budaszewski, Renata; von Messling, Veronika

    2016-01-01

    Morbilliviruses share considerable structural and functional similarities. Even though disease severity varies among the respective host species, the underlying pathogenesis and the clinical signs are comparable. Thus, insights gained with one morbillivirus often apply to the other members of the genus. Since the Canine distemper virus (CDV) causes severe and often lethal disease in dogs and ferrets, it is an attractive model to characterize morbillivirus pathogenesis mechanisms and to evaluate the efficacy of new prophylactic and therapeutic approaches. This review compares the cellular tropism, pathogenesis, mechanisms of persistence and immunosuppression of the Measles virus (MeV) and CDV. It then summarizes the contributions made by studies on the CDV in dogs and ferrets to our understanding of MeV pathogenesis and to vaccine and drugs development. PMID:27727184

  15. Epizootic canine distemper virus infection among wild mammals.

    PubMed

    Kameo, Yuki; Nagao, Yumiko; Nishio, Yohei; Shimoda, Hiroshi; Nakano, Hitoshi; Suzuki, Kazuo; Une, Yumi; Sato, Hiroshi; Shimojima, Masayuki; Maeda, Ken

    2012-01-27

    In the spring of 2007, seven raccoon dogs and a weasel were captured near the city of Tanabe in Wakayama prefecture, Japan. The causative agent of the animals' death 1-2 days after capture was identified as canine distemper virus (CDV) by virus isolation, immunostaining with an anti-CDV polyclonal antibody, and a commercially available CDV antigen-detection kit. Sequence analysis of hemagglutinin genes indicated the isolated viruses belong to genotype Asia-1 and possess the substitution from tyrosine (Y) to histidine (H) at position 549 that is associated with the spread of CDV to non-canine hosts. A serosurvey for CDV was then conducted among wild animals in the region. The animals assayed consisted of 104 raccoons, 41 wild boars, 19 raccoon dogs, five Sika deer, two badgers, one weasel, one marten, one Siberian weasel and one fox. Virus-neutralization (VN) tests showed that, except for fox and weasel, all of the species assayed had VN antibodies to CDV. Interestingly, 11 of the 41 wild boars (27%) and two of the five Sika deer assayed possessed VN antibodies to CDV. These findings indicate that CDV infection was widespread among wild mammals during this epizootic.

  16. Phylogenetic characterization of canine distemper viruses detected in naturally infected dogs in North America.

    PubMed

    Pardo, Ingrid D R; Johnson, Gayle C; Kleiboeker, Steven B

    2005-10-01

    In 2004, six puppies and one adult dog from a total of four premises were subjected to necropsy evaluation. For five of the seven dogs, disease caused by canine distemper virus (CDV) infection was suspected based on clinical signs. In all of the dogs, a diagnosis of CDV infection was established by the presence of compatible gross and histologic lesions, immunohistochemical labeling for CDV antigen, and detection of CDV RNA by reverse transcription-PCR. To further characterize the CDV strains detected in the four cases, complete gene sequences were determined for the hemagglutinin (H) and fusion (F) protein genes, while partial gene sequencing was performed for the phosphoprotein gene. A total of 4,508 bases were sequenced for the CDV strains detected from each of the four cases. Two cases were found to have identical sequences except for 2 bases in the intergenic region of the F and H genes. Phylogenetic analysis strongly suggested an evolutionary relationship between sequences detected in these two cases and those of phocine distemper virus 2 and two other strains of CDV not previously detected in the continental United States. Clear phylogenetic relationships were not established for viruses detected in the two additional cases; however, one strain showed similarity to CDV strains detected in a panda from China. Importantly, the three CDV strains detected were demonstrated to be genetically distinct from known vaccine strains and strains previously reported in the continental United States.

  17. New aspects of the pathogenesis of canine distemper leukoencephalitis.

    PubMed

    Lempp, Charlotte; Spitzbarth, Ingo; Puff, Christina; Cana, Armend; Kegler, Kristel; Techangamsuwan, Somporn; Baumgärtner, Wolfgang; Seehusen, Frauke

    2014-07-02

    Canine distemper virus (CDV) is a member of the genus morbillivirus, which is known to cause a variety of disorders in dogs including demyelinating leukoencephalitis (CDV-DL). In recent years, substantial progress in understanding the pathogenetic mechanisms of CDV-DL has been made. In vivo and in vitro investigations provided new insights into its pathogenesis with special emphasis on axon-myelin-glia interaction, potential endogenous mechanisms of regeneration, and astroglial plasticity. CDV-DL is characterized by lesions with a variable degree of demyelination and mononuclear inflammation accompanied by a dysregulated orchestration of cytokines as well as matrix metalloproteinases and their inhibitors. Despite decades of research, several new aspects of the neuropathogenesis of CDV-DL have been described only recently. Early axonal damage seems to represent an initial and progressive lesion in CDV-DL, which interestingly precedes demyelination. Axonopathy may, thus, function as a potential trigger for subsequent disturbed axon-myelin-glia interactions. In particular, the detection of early axonal damage suggests that demyelination is at least in part a secondary event in CDV-DL, thus challenging the dogma of CDV as a purely primary demyelinating disease. Another unexpected finding refers to the appearance of p75 neurotrophin (NTR)-positive bipolar cells during CDV-DL. As p75NTR is a prototype marker for immature Schwann cells, this finding suggests that Schwann cell remyelination might represent a so far underestimated endogenous mechanism of regeneration, though this hypothesis still remains to be proven. Although it is well known that astrocytes represent the major target of CDV infection in CDV-DL, the detection of infected vimentin-positive astrocytes in chronic lesions indicates a crucial role of this cell population in nervous distemper. While glial fibrillary acidic protein represents the characteristic intermediate filament of mature astrocytes

  18. Jaundice and bilirubinemia as manifestations of canine distemper in raccoons and ferrets

    USGS Publications Warehouse

    Kilham, L.; Habermann, R.T.; Herman, C.M.

    1956-01-01

    1) Two strains of distemper virus have been isolated from wild raccoons and one strain from ferrets. 2) All strains isolated have induced bilirubinemia in raccoons and ferrets. Many raccoons with bilirubinemia also had jaundice. 3) Identification of these strains as members of the canine distemper virus complex has been by clinical and pathological findings consistent with this diagnosis as well as by cross-immunity tests.

  19. Comparison of the immunofluorescence assay with RT-PCR and nested PCR in the diagnosis of canine distemper.

    PubMed

    Jóźwik, A; Frymus, T

    2005-05-01

    Two pairs of primers were prepared, both localized within the sequences of the nucleoprotein gene (NP) of canine distemper virus (CDV). A number of experiments were done to optimize the conditions of RT-PCR and nested PCR methods. The nucleic acids of the Onderstepoort, Rockborn, Snyder Hill and Lederle strains of CDV could be detected with these primers. However, they did not react with the sequences of the Edmonston strain of the measles virus. The detection limit for RT-PCR was 10 TCID50 and for nested PCR 0.1 TCID50 of CDV. The RT-PCR was able to demonstrate the nucleic acid of CDV in the blood of all seven puppies vaccinated with a modified live virus. Blood samples of 23 dogs clinically suspected of distemper were examined by RT-PCR combined with nested PCR, and the results were compared with the detection of the CDV antigen in the smears from the mucous membranes by the direct immunofluorescence (IF) test. Of the 23 dogs, 12 were positive in nested PCR, six in the IF assay, and only two in single RT-PCR. It is concluded that nested PCR seems to be the most sensitive method for ante-mortem diagnosis of canine distemper, especially in its subacute or chronic forms.

  20. Canine distemper virus (CDV) in another big cat: should CDV be renamed carnivore distemper virus?

    PubMed

    Terio, Karen A; Craft, Meggan E

    2013-09-17

    One of the greatest threats to the conservation of wild cat populations may be dogs or, at least, one of their viruses. Canine distemper virus (CDV), a single-stranded RNA virus in the Paramyxoviridae family and genus Morbillivirus, infects and causes disease in a variety of species, not just canids. An outbreak of CDV in wild lions in the Serengeti, Tanzania, in 1994 was a wake-up call for conservationists, as it demonstrated that an infectious disease could swiftly impact a previously healthy felid population. To understand how this virus causes disease in noncanid hosts, researchers have focused on specific mutations in the binding site of the CDV hemagglutinin gene. Now, Seimon et al. provide information on CDV in its latest feline victim, the endangered wild Amur tiger (Panthera tigris altaica) [T. A. Seimon et al., mBio 4(4):e00410-13, 2013, doi:10.1128/mBio.00410-13]. Their findings of CDV strains infecting tigers, in combination with recent information from other felids, paints a different picture, one in which CDV strains from a variety of geographic lineages and with a variety of amino acid residues in the hemagglutinin gene binding site can infect cats and cause disease. Although CDV has been known as a multihost disease since its discovery in domestic dogs in 1905, perhaps it is time to reconsider whether these noncanid species are not just incidental or "spillover" hosts but, rather, a normal part of the complex ecology of this infectious disease.

  1. Antibody titers for canine parvovirus type-2, canine distemper virus, and canine adenovirus type-1 in adult household dogs.

    PubMed

    Taguchi, Masayuki; Namikawa, Kazuhiko; Maruo, Takuya; Orito, Kensuke; Lynch, Jonathan; Sahara, Hiroeki

    2011-09-01

    Serum antibody titers for canine parvovirus type-2 (CPV-2), canine distemper virus (CDV) and canine adenovirus type-1 (CAV-1) were investigated in 1031 healthy adult household dogs (2 to 18 years old) given an annual inoculation in the previous 11 to 13 months. The number of dogs retaining significant titers of antibodies against CPV-2, CDV, and CAV-1 were 888 (86%), 744 (72%), and 732 (71%), respectively. There were no differences between males and females in antibody titers against the 3 viruses. Antibody titer for CPV-2 was significantly higher in younger dogs than in older dogs, CDV antibody was significantly higher in older dogs than in younger dogs, and CAV titer was not associated with age.

  2. Antibody titers for canine parvovirus type-2, canine distemper virus, and canine adenovirus type-1 in adult household dogs

    PubMed Central

    Taguchi, Masayuki; Namikawa, Kazuhiko; Maruo, Takuya; Orito, Kensuke; Lynch, Jonathan; Sahara, Hiroeki

    2011-01-01

    Serum antibody titers for canine parvovirus type-2 (CPV-2), canine distemper virus (CDV) and canine adenovirus type-1 (CAV-1) were investigated in 1031 healthy adult household dogs (2 to 18 years old) given an annual inoculation in the previous 11 to 13 months. The number of dogs retaining significant titers of antibodies against CPV-2, CDV, and CAV-1 were 888 (86%), 744 (72%), and 732 (71%), respectively. There were no differences between males and females in antibody titers against the 3 viruses. Antibody titer for CPV-2 was significantly higher in younger dogs than in older dogs, CDV antibody was significantly higher in older dogs than in younger dogs, and CAV titer was not associated with age. PMID:22379198

  3. Canine Distemper Virus in Wild Felids of Costa Rica.

    PubMed

    Avendaño, Roberto; Barrueta, Flor; Soto-Fournier, Sofía; Chavarría, Max; Monge, Otto; Gutiérrez-Espeleta, Gustavo A; Chaves, Andrea

    2016-04-28

    Several highly infectious diseases can be transmitted through feces and cause elevated mortality among carnivore species. One such infectious agent, canine distemper virus (CDV; Paramyxoviridae: Morbillivirus), has been reported to affect wild carnivores, among them several felid species. We screened free-ranging and captive wild carnivores in Costa Rica for CDV. Between 2006 and 2012, we collected 306 fecal samples from 70 jaguars (Panther onca), 71 ocelots ( Leopardus pardalis ), five jaguarundis (Puma yaguaroundi), 105 pumas ( Puma concolor ), five margays ( Leopardus wiedii ), 23 coyotes ( Canis latrans ), and 27 undetermined Leopardus spp. We found CDV in six individuals: one captive jaguarundi (rescued in 2009), three free-ranging ocelots (samples collected in 2012), and two free-ranging pumas (samples collected in 2007). Phylogenetic analyses were performed using sequences of the phosphoprotein (P) gene. We provide evidence of CDV in wild carnivores in Costa Rica and sequence data from a Costa Rican CDV isolate, adding to the very few sequence data available for CDV isolates from wild Central American carnivores.

  4. A canine distemper virus epidemic in Serengeti lions (Panthera leo).

    PubMed

    Roelke-Parker, M E; Munson, L; Packer, C; Kock, R; Cleaveland, S; Carpenter, M; O'Brien, S J; Pospischil, A; Hofmann-Lehmann, R; Lutz, H; Mwamengele, G L; Mgasa, M N; Machange, G A; Summers, B A; Appel, M J

    1996-02-01

    Canine distemper virus (CDV) is thought to have caused several fatal epidemics in canids within the Serengeti-Mara ecosystem of East Africa, affecting silver-backed jackals (Canis mesomelas) and bat-eared foxes (Otocyon megalotis) in 1978 (ref. 1), and African wild dogs (Lycaon pictus) in 1991 (refs 2, 3). The large, closely monitored Serengeti lion population was not affected in these epidemics. However, an epidemic caused by a morbillivirus closely related to CDV emerged abruptly in the lion population of the Serengeti National Park, Tanzania, in early 1994, resulting in fatal neurological disease characterized by grand mal seizures and myoclonus; the lions that died had encephalitis and pneumonia. Here we report the identification of CDV from these lions, and the close phylogenetic relationship between CDV isolates from lions and domestic dogs. By August 1994, 85% of the Serengeti lion population had anti-CDV antibodies, and the epidemic spread north to lions in the Maasai Mara National reserve, Kenya, and uncounted hyaenas, bat-eared foxes, and leopards were also affected.

  5. Could Epstein-Barr virus or canine distemper virus cause multiple sclerosis?

    PubMed

    Lincoln, John A; Hankiewicz, Karolina; Cook, Stuart D

    2008-08-01

    Multiple sclerosis (MS) is thought to be an immune-mediated disease with a possible environmental trigger. Genetic and environmental factors, including infection by pathogens, may act synergistically to trigger the disease. There is growing epidemiologic, serologic, and pathologic evidence that Epstein-Barr virus may cause MS or contribute to its pathogenesis. The evidence that canine distemper virus is involved in MS is less robust. More definitive data are required to prove that Epstein-Barr virus or canine distemper virus causes some or most cases of MS.

  6. Efficacy of Recombinant Canine Distemper Virus Expressing Leishmania Antigen against Leishmania Challenge in Dogs.

    PubMed

    Miura, Ryuichi; Kooriyama, Takanori; Yoneda, Misako; Takenaka, Akiko; Doki, Miho; Goto, Yasuyuki; Sanjoba, Chizu; Endo, Yasuyuki; Fujiyuki, Tomoko; Sugai, Akihiro; Tsukiyama-Kohara, Kyoko; Matsumoto, Yoshitsugu; Sato, Hiroki; Kai, Chieko

    2015-01-01

    Canine distemper virus (CDV) vaccination confers long-term protection against CDV reinfection. To investigate the utility of CDV as a polyvalent vaccine vector for Leishmania, we generated recombinant CDVs, based on an avirulent Yanaka strain, that expressed Leishmania antigens: LACK, TSA, or LmSTI1 (rCDV-LACK, rCDV-TSA, and rCDV-LmSTI1, respectively). Dogs immunized with rCDV-LACK were protected against challenge with lethal doses of virulent CDV, in the same way as the parental Yanaka strain. To evaluate the protective effects of the recombinant CDVs against cutaneous leishmaniasis in dogs, dogs were immunized with one recombinant CDV or a cocktail of three recombinant CDVs, before intradermal challenge (in the ears) with infective-stage promastigotes of Leishmania major. Unvaccinated dogs showed increased nodules with ulcer formation after 3 weeks, whereas dogs immunized with rCDV-LACK showed markedly smaller nodules without ulceration. Although the rCDV-TSA- and rCDV-LmSTI1-immunized dogs showed little protection against L. major, the cocktail of three recombinant CDVs more effectively suppressed the progression of nodule formation than immunization with rCDV-LACK alone. These results indicate that recombinant CDV is suitable for use as a polyvalent live attenuated vaccine for protection against both CDV and L. major infections in dogs.

  7. Efficacy of Recombinant Canine Distemper Virus Expressing Leishmania Antigen against Leishmania Challenge in Dogs

    PubMed Central

    Yoneda, Misako; Takenaka, Akiko; Doki, Miho; Goto, Yasuyuki; Sanjoba, Chizu; Endo, Yasuyuki; Fujiyuki, Tomoko; Sugai, Akihiro; Tsukiyama-Kohara, Kyoko; Matsumoto, Yoshitsugu; Sato, Hiroki; Kai, Chieko

    2015-01-01

    Canine distemper virus (CDV) vaccination confers long-term protection against CDV reinfection. To investigate the utility of CDV as a polyvalent vaccine vector for Leishmania, we generated recombinant CDVs, based on an avirulent Yanaka strain, that expressed Leishmania antigens: LACK, TSA, or LmSTI1 (rCDV–LACK, rCDV–TSA, and rCDV–LmSTI1, respectively). Dogs immunized with rCDV-LACK were protected against challenge with lethal doses of virulent CDV, in the same way as the parental Yanaka strain. To evaluate the protective effects of the recombinant CDVs against cutaneous leishmaniasis in dogs, dogs were immunized with one recombinant CDV or a cocktail of three recombinant CDVs, before intradermal challenge (in the ears) with infective-stage promastigotes of Leishmania major. Unvaccinated dogs showed increased nodules with ulcer formation after 3 weeks, whereas dogs immunized with rCDV–LACK showed markedly smaller nodules without ulceration. Although the rCDV–TSA- and rCDV–LmSTI1-immunized dogs showed little protection against L. major, the cocktail of three recombinant CDVs more effectively suppressed the progression of nodule formation than immunization with rCDV–LACK alone. These results indicate that recombinant CDV is suitable for use as a polyvalent live attenuated vaccine for protection against both CDV and L. major infections in dogs. PMID:26162094

  8. Phylogenetic evidence of a new canine distemper virus lineage among domestic dogs in Colombia, South America.

    PubMed

    Espinal, Maria A; Díaz, Francisco J; Ruiz-Saenz, Julian

    2014-08-06

    Canine distemper virus (CDV) is a highly contagious viral disease of carnivores affecting both wild and domestic populations. The hemagglutinin gene, encoding for the attachment protein that determines viral tropism, shows high heterogeneity among strains, allowing for the distinction of ten different lineages distributed worldwide according to a geographic pattern. We obtained the sequences of the full-length H gene of 15 wild-type CDV strains circulating in domestic dog populations from the Aburrá Valley, Colombia. A phylogenetic analysis of H gene nucleotide sequences from Colombian CDV viruses along with field isolates from different geographic regions and vaccine strains was performed. Colombian wild-type viruses formed a distinct monophyletic cluster clearly separated from the previously identified wild-type and vaccine lineages, suggesting that a novel genetic variant, quite different from vaccines and other lineages, is circulating among dog populations in the Aburrá Valley. We propose naming this new lineage as "South America 3". This information indicates that there are at least three different CDV lineages circulating in domestic and wild carnivore populations in South America. The first one, renamed Europe/South America 1, circulates in Brazil and Uruguay; the second, South America 2, appears to be restricted to Argentina; and the third, South America 3, which comprises all the strains characterized in this study, may also be circulating in other northern countries of South America.

  9. Concomitant canine distemper, infectious canine hepatitis, canine parvoviral enteritis, canine infectious tracheobronchitis, and toxoplasmosis in a puppy.

    PubMed

    Headley, Selwyn Arlington; Alfieri, Amauri Alcindo; Fritzen, Juliana Torres Tomazi; Garcia, João Luis; Weissenböck, Herbert; da Silva, Ana Paula; Bodnar, Livia; Okano, Werner; Alfieri, Alice Fernandes

    2013-01-01

    The concomitant infections of Canine distemper virus (CDV), Canine adenovirus A types 1 (CAdV-1) and 2 (CAdV-2), Canine parvovirus type 2 (CPV-2), and Toxoplasma gondii are described in a 43-day-old mixed-breed puppy. Clinically, there were convulsions and blindness with spontaneous death; 14 siblings of this puppy, born to a 10-month-old dam, which was seropositive (titer: 1,024) for T. gondii, also died. Necropsy revealed unilateral corneal edema (blue eye), depletion of intestinal lymphoid tissue, non-collapsible lungs, congestion of meningeal vessels, and a pale area in the myocardium. Histopathology demonstrated necrotizing myocarditis associated with intralesional apicomplexan protozoa; necrotizing and chronic hepatitis associated with rare intranuclear inclusion bodies within hepatocytes; necrotizing bronchitis and bronchiolitis; interstitial pneumonia associated with eosinophilic intracytoplasmic inclusion bodies within epithelial cells; atrophy and fusion of intestinal villi with cryptal necrosis; and white matter demyelination of the cerebrum and cerebellum associated with intranuclear inclusion bodies within astrocytes. Polymerase chain reaction (PCR) amplified the partial fragments (bp) of the CDV N gene (290 bp), CPV-2c VP2 capsid protein gene (583 bp), and CAdV-1 (508 bp) and CAdV-2 (1,030 bp) E gene from urine and tissue samples. The PCR assays demonstrated that the apicomplexan protozoa observed within several organs contained DNA specific for T. gondii; genotyping revealed T. gondii type III. The findings support the characterization of concomitant infections of CDV, CAdV-1, CAdV-2, CPV-2, and T. gondii in this puppy. Further, seroreactivity to T. gondii of the dam in association with the systemic disease observed in the puppy described herein is suggestive of congenital toxoplasmosis.

  10. Recombinant Newcastle disease viral vector expressing hemagglutinin or fusion of canine distemper virus is safe and immunogenic in minks.

    PubMed

    Ge, Jinying; Wang, Xijun; Tian, Meijie; Gao, Yuwei; Wen, Zhiyuan; Yu, Guimei; Zhou, Weiwei; Zu, Shulong; Bu, Zhigao

    2015-05-15

    Canine Distemper Virus (CDV) infects many carnivores and cause several high-mortality disease outbreaks. The current CDV live vaccine cannot be safely used in some exotic species, such as mink and ferret. Here, we generated recombinant lentogenic Newcastle disease virus (NDV) LaSota expressing either envelope glycoproyein, heamagglutinine (H) or fusion protein (F), named as rLa-CDVH and rLa-CDVF, respectively. The feasibility of these recombinant NDVs to serve as live virus-vectored CD vaccine was evaluated in minks. rLa-CDVH induced significant neutralization antibodies (NA) to CDV and provided solid protection against virulent CDV challenge. On the contrast, rLa-CDVF induced much lower NA to CDV and fail to protected mink from virulent CDV challenge. Results suggest that recombinant NDV expressing CDV H is safe and efficient candidate vaccine against CDV in mink, and maybe other host species.

  11. Canine Distemper Virus (CDV) in Another Big Cat: Should CDV Be Renamed Carnivore Distemper Virus?

    PubMed Central

    Terio, Karen A.; Craft, Meggan E.

    2013-01-01

    ABSTRACT One of the greatest threats to the conservation of wild cat populations may be dogs or, at least, one of their viruses. Canine distemper virus (CDV), a single-stranded RNA virus in the Paramyxoviridae family and genus Morbillivirus, infects and causes disease in a variety of species, not just canids. An outbreak of CDV in wild lions in the Serengeti, Tanzania, in 1994 was a wake-up call for conservationists, as it demonstrated that an infectious disease could swiftly impact a previously healthy felid population. To understand how this virus causes disease in noncanid hosts, researchers have focused on specific mutations in the binding site of the CDV hemagglutinin gene. Now, Seimon et al. provide information on CDV in its latest feline victim, the endangered wild Amur tiger (Panthera tigris altaica) [T. A. Seimon et al., mBio 4(4):e00410-13, 2013, doi:10.1128/mBio.00410-13]. Their findings of CDV strains infecting tigers, in combination with recent information from other felids, paints a different picture, one in which CDV strains from a variety of geographic lineages and with a variety of amino acid residues in the hemagglutinin gene binding site can infect cats and cause disease. Although CDV has been known as a multihost disease since its discovery in domestic dogs in 1905, perhaps it is time to reconsider whether these noncanid species are not just incidental or “spillover” hosts but, rather, a normal part of the complex ecology of this infectious disease. PMID:24045642

  12. Canine distemper virus--a morbillivirus in search of new hosts?

    PubMed

    Harder, T C; Osterhaus, A D

    1997-03-01

    Canine distemper morbillivirus (CDV) induces a multisystemic, often fatal disease in a wide and seemingly expanding host range among the Carnivora. Several genotypes of an otherwise monotypic virus species co-circulate in a geographically restricted pattern. Interspecies transmissions frequently occur, often leading to devastating epizootics in highly susceptible or immunologically naive populations.

  13. Canine distemper viruses expressing a hemagglutinin without N-glycans lose virulence but retain immunosuppression.

    PubMed

    Sawatsky, Bevan; von Messling, Veronika

    2010-03-01

    Paramyxovirus glycoproteins are posttranslationally modified by the addition of N-linked glycans, which are often necessary for correct folding, processing, and cell surface expression. To establish the contribution of N glycosylation to morbillivirus attachment (H) protein function and overall virulence, we first determined the use of the potential N-glycosylation sites in the canine distemper virus (CDV) H proteins. Biochemical characterization revealed that the three sites conserved in all strains were N glycosylated, whereas only two of the up to five additional sites present in wild-type strains are used. A wild-type virus with an H protein reproducing the vaccine strain N-glycosylation pattern remained lethal in ferrets but with a prolonged course of disease. In contrast, introduction of the vaccine H protein in the wild-type context resulted in complete attenuation. To further characterize the role of N glycosylation in CDV pathogenesis, the N-glycosylation sites of wild-type H proteins were successively deleted, including a nonstandard site, to ultimately generate a nonglycosylated H protein. Despite reduced expression levels, this protein remained fully functional. Recombinant viruses expressing N-glycan-deficient H proteins no longer caused disease, even though their immunosuppressive capacities were retained, indicating that reduced N glycosylation contributes to attenuation without affecting immunosuppression.

  14. Pathogenesis and phylogenetic analyses of canine distemper virus strain 007Lm, a new isolate in dogs.

    PubMed

    Lan, N T; Yamaguchi, R; Furuya, Y; Inomata, A; Ngamkala, S; Naganobu, K; Kai, K; Mochizuki, M; Kobayashi, Y; Uchida, K; Tateyama, S

    2005-10-31

    The pathogenesis of a new isolate of canine distemper virus (CDV), strain 007Lm, was investigated from lymph node tissue by using Vero cells that express canine signalling lymphocyte activation molecules with a tag (Vero-DST) in dogs. Two CDV sero-negative Beagle dogs were inoculated intranasally and intraconjunctively with a virus suspension. Both infected dogs showed clinical signs of severe bloody diarrhea, conjunctivitis, ocular discharge, nasal discharge and coughing, lymphopenia, fever and weight loss. Titers of CDV-IgM and CDV-IgG in the blood were measured. CDV was detected by using reverse transcriptase-PCR and was recovered in swabs from one dog from 9 days and from the other dogs from 10 days after inoculation. Molecular and phylogenetic analyses of H and P genes showed that nucleotide and amino acid sequences of these genes of strain 007Lm after isolation in Vero-DST cells are identical to those of the original virus from fresh tissue and that strain 007Lm joins to the Asia 2 group cluster of CDV strains that is distinct from other clusters. These results indicate that (1) CDV strain 007Lm isolated in Vero-DST cells is virulent, (2) nucleotide and amino acid sequences of H and P genes of strain 007Lm do not change after isolation in Vero-DST cells compared with the original virus from fresh tissue and (3) strain 007Lm isolated from a vaccinated dog belongs to a cluster far from the vaccine strains in the phylogenetic trees of H and P genes.

  15. Immunization with plasmid DNA encoding the hemagglutinin and the nucleoprotein confers robust protection against a lethal canine distemper virus challenge.

    PubMed

    Dahl, Lotte; Jensen, Trine Hammer; Gottschalck, Elisabeth; Karlskov-Mortensen, Peter; Jensen, Tove Dannemann; Nielsen, Line; Andersen, Mads Klindt; Buckland, Robin; Wild, T Fabian; Blixenkrone-Møller, Merete

    2004-09-09

    We have investigated the protective effect of immunization of a highly susceptible natural host of canine distemper virus (CDV) with DNA plasmids encoding the viral nucleoprotein (N) and hemagglutinin (H). The combined intradermal and intramuscular routes of immunization elicited high virus-neutralizing serum antibody titres in mink (Mustela vison). To mimic natural exposure, we also conducted challenge infection by horizontal transmission from infected contact animals. Other groups received a lethal challenge infection by administration to the mucosae of the respiratory tract and into the muscle. One of the mink vaccinated with N plasmid alone developed severe disease after challenge. In contrast, vaccination with the H plasmid together with the N plasmid conferred solid protection against disease and we were unable to detect CDV infection in PBMCs or in different tissues after challenge. Our findings show that DNA immunization by the combined intradermal and intramuscular routes can confer solid protective immunity against naturally transmitted morbillivirus infection and disease.

  16. Protective levels of canine distemper virus antibody in an urban dog population using plaque reduction neutralization test.

    PubMed

    Oyedele, O I; Oluwayelu, D O; Cadmus, S I B; Odemuyiwa, S O; Adu, F D

    2004-09-01

    Blood samples from 50 dogs were collected at three veterinary clinics in Ibadan and Abuja, Nigeria and the serum from each sample was evaluated serologically for neutralizing antibodies against canine distemper virus (CDV) by the highly sensitive plaque reduction (PRN) neutralization assay. Thirteen dogs had plaque reduction neutralization titres of 0-100, seven had titres of 100-1,000 while 30 had titres ranging from 1,000-6,000. The PRN titres of vaccinated dogs were found to be significantly higher than unvaccinated dogs. The widespread use of the highly reproducible PRN test for the evaluation of antibody response to CDV may be very important in the generation of international CDV positive serum standards that should help to improve pre-and post-vaccination testing of dogs worldwide.

  17. Phylogenetic analysis of the haemagglutinin gene of canine distemper virus strains detected from giant panda and raccoon dogs in China

    PubMed Central

    2013-01-01

    Background Canine distemper virus (CDV) infects a variety of carnivores, including wild and domestic Canidae. In this study, we sequenced and phylogenetic analyses of the hemagglutinin (H) genes from eight canine distemper virus (CDV) isolates obtained from seven raccoon dogs (Nyctereutes procyonoides) and a giant panda (Ailuropoda melanoleuca) in China. Results Phylogenetic analysis of the partial hemagglutinin gene sequences showed close clustering for geographic lineages, clearly distinct from vaccine strains and other wild-type foreign CDV strains, all the CDV strains were characterized as Asia-1 genotype and were highly similar to each other (91.5-99.8% nt and 94.4-99.8% aa). The giant panda and raccoon dogs all were 549Y on the HA protein in this study, irrespective of the host species. Conclusions These findings enhance our knowledge of the genetic characteristics of Chinese CDV isolates, and may facilitate the development of effective strategies for monitoring and controlling CDV for wild canids and non-cainds in China. PMID:23566727

  18. Nectin4 is an epithelial cell receptor for canine distemper virus and involved in neurovirulence.

    PubMed

    Pratakpiriya, Watanyoo; Seki, Fumio; Otsuki, Noriyuki; Sakai, Kouji; Fukuhara, Hideo; Katamoto, Hiromu; Hirai, Takuya; Maenaka, Katsumi; Techangamsuwan, Somporn; Lan, Nguyen Thi; Takeda, Makoto; Yamaguchi, Ryoji

    2012-09-01

    Canine distemper virus (CDV) uses signaling lymphocyte activation molecule (SLAM), expressed on immune cells, as a receptor. However, epithelial and neural cells are also affected by CDV in vivo. Wild-type CDV strains showed efficient replication with syncytia in Vero cells expressing dog nectin4, and the infection was blocked by an anti-nectin4 antibody. In dogs with distemper, CDV antigen was preferentially detected in nectin4-positive neurons and epithelial cells, suggesting that nectin4 is an epithelial cell receptor for CDV and also involved in its neurovirulence.

  19. Nectin4 Is an Epithelial Cell Receptor for Canine Distemper Virus and Involved in Neurovirulence

    PubMed Central

    Pratakpiriya, Watanyoo; Seki, Fumio; Otsuki, Noriyuki; Sakai, Kouji; Fukuhara, Hideo; Katamoto, Hiromu; Hirai, Takuya; Maenaka, Katsumi; Techangamsuwan, Somporn; Lan, Nguyen Thi; Takeda, Makoto

    2012-01-01

    Canine distemper virus (CDV) uses signaling lymphocyte activation molecule (SLAM), expressed on immune cells, as a receptor. However, epithelial and neural cells are also affected by CDV in vivo. Wild-type CDV strains showed efficient replication with syncytia in Vero cells expressing dog nectin4, and the infection was blocked by an anti-nectin4 antibody. In dogs with distemper, CDV antigen was preferentially detected in nectin4-positive neurons and epithelial cells, suggesting that nectin4 is an epithelial cell receptor for CDV and also involved in its neurovirulence. PMID:22761370

  20. Three-year serologic immunity against canine parvovirus type 2 and canine adenovirus type 2 in dogs vaccinated with a canine combination vaccine.

    PubMed

    Larson, L J; Schultz, R D

    2007-01-01

    A group of client-owned dogs and a group of dogs at a commercial kennel were evaluated for duration of antibody responses against canine parvovirus type 2 (CPV-2) and canine adenovirus type 1 (CAV-1) after receiving a combination vaccine containing recombinant canarypox-vectored canine distemper virus (CDV) and modified-live CPV-2, CAV-2, and canine parainfluenza virus, with (C6) or without (C4) two serovars of Leptospira (Recombitek C4 or C6, Merial). Duration of antibody, which correlates with protective immunity, was found to be at least 36 months in both groups. Recombitek combination vaccines can confidently be given every 3 years with assurance of protection in immunocompetent dogs against CPV-2 and CAV-1 as well as CDV. This allows this combination vaccine, like other, similar modified- live virus combination products containing CDV, CAV-2, and CPV-2, to be administered in accordance with the recommendations of the American Animal Hospital Association Canine Vaccine Task Force.

  1. Prevalence of antibodies against canine distemper virus and canine parvovirus among foxes and wolves from Spain.

    PubMed

    Sobrino, R; Arnal, M C; Luco, D F; Gortázar, C

    2008-01-01

    Viral diseases can influence the population dynamics of wild carnivores and can have effects on carnivore conservation. Hence, a serologic survey was conducted in an opportunistic sample of 137 foxes (Vulpes vulpes) and 37 wolves (Canis lupus) in Spain for 1997-2007 to detect antibodies against canine distemper virus (CDV) and against canine parvovirus (CPV) by indirect ELISA. Antibodies against CDV were detected in 18.7% of the analyzed animals and antibodies against CPV in 17.2%. There was no difference in antibody prevalence to CDV between both species, even in the same region (P>0.05), but there was a significant difference in antibody prevalence to CPV between foxes (5.1%) and wolves (62.2%) (P<0.05). In fox populations there was a significant difference in antibody prevalence to CDV between geographic areas (Aragón 26.4%, La Mancha 7.8%, P<0.05). In wolf populations there was significantly higher antibody prevalence against CPV (P<0.05) in Castilla y León (100%) than in the Cantabric region (53.3%). There was no significant sex or age-related difference in the antibody prevalence against CDV or CPV in foxes. These results indicate that contact with CDV is widespread among wild canid populations in Spain and that CPV is endemic in the Iberian wolf population. The implications of these results are briefly discussed.

  2. Phylogenetic analysis of Austrian canine distemper virus strains from clinical samples from dogs and wild carnivores.

    PubMed

    Benetka, V; Leschnik, M; Affenzeller, N; Möstl, K

    2011-04-09

    Austrian field cases of canine distemper (14 dogs, one badger [Meles meles] and one stone marten [Martes foina]) from 2002 to 2007 were investigated and the case histories were summarised briefly. Phylogenetic analysis of fusion (F) and haemagglutinin (H) gene sequences revealed different canine distemper virus (CDV) lineages circulating in Austria. The majority of CDV strains detected from 2002 to 2004 were well embedded in the European lineage. One Austrian canine sample detected in 2003, with a high similarity to Hungarian sequences from 2005 to 2006, could be assigned to the Arctic group (phocine distemper virus type 2-like). The two canine sequences from 2007 formed a clearly distinct group flanked by sequences detected previously in China and the USA on an intermediate position between the European wildlife and the Asia-1 cluster. The Austrian wildlife strains (2006 and 2007) could be assigned to the European wildlife group and were most closely related to, yet clearly different from, the 2007 canine samples. To elucidate the epidemiological role of Austrian wildlife in the transmission of the disease to dogs and vice versa, H protein residues related to receptor and host specificity (residues 530 and 549) were analysed. All samples showed the amino acids expected for their host of origin, with the exception of a canine sequence from 2007, which had an intermediate position between wildlife and canine viral strains. In the period investigated, canine strains circulating in Austria could be assigned to four different lineages reflecting both a high diversity and probably different origins of virus introduction to Austria in different years.

  3. Expression of a foreign gene by recombinant canine distemper virus recovered from cloned DNAs.

    PubMed

    Parks, Christopher L; Wang, Hai-Ping; Kovacs, Gerald R; Vasilakis, Nikos; Kowalski, Jacek; Nowak, Rebecca M; Lerch, Robert A; Walpita, Pramila; Sidhu, Mohinderjit S; Udem, Stephen A

    2002-02-26

    A canine distemper virus (CDV) genomic cDNA clone and expression plasmids required to establish a CDV rescue system were generated from a laboratory-adapted strain of the Onderstepoort vaccine virus. In addition, a CDV minireplicon was prepared and used in transient expression studies performed to identify optimal virus rescue conditions. Results from the transient expression experiments indicated that minireplicon-encoded reporter gene activity was increased when transfected cell cultures were maintained at 32 rather than 37 degrees C, and when the cellular stress response was induced by heat shock. Applying these findings to rescue of recombinant CDV (rCDV) resulted in efficient recovery of virus after transfected HEp2 or A549 cells were co-cultured with Vero cell monolayers. Nucleotide sequence determination and analysis of restriction site polymorphisms confirmed that rescued virus was rCDV. A rCDV strain also was engineered that contained the luciferase gene inserted between the P and M genes; this virus directed high levels of luciferase expression in infected cells.

  4. Phylogenetic characterization of canine distemper virus isolates from naturally infected dogs and a marten in Korea.

    PubMed

    An, Dong-Jun; Yoon, Sook-Hee; Park, Jee-Yong; No, In-Sun; Park, Bong-Kyun

    2008-12-10

    We sequenced the hemagglutinin (H) genes from four canine distemper virus (CDV) isolates obtained from three dogs and a marten in Korea. These sequences were included in subsequent H gene-focused phylogenetic tree analysis of 89 CDV strains. This analysis revealed eight clades designated as EU1, EU2, EU3, NA1, NA2, Asia 1, Asia 2 and Vaccine. Three of the Korean isolates (97Jindo, 98Marten and 07D111) occurred in the Asia 2 group that also contains many Japanese CDV strains isolated in 1998. The remaining Korean strain (07Q72) fell into the Asia 1 group. The 21 H protein sequences of 25 Asia 1 strains are generally predicted to bear nine potential N-linked glycosylation sites. In contrast, the 9 H protein sequences of 12 Asia 2 strains had eight potential N-linked glycosylation sites. The remaining strains had six (98Marten and 07D111) and seven (97Jindo) potential N-linked glycosylation sites.

  5. Importance of canine distemper virus (CDV) infection in free-ranging Iberian lynxes (Lynx pardinus).

    PubMed

    Meli, Marina L; Simmler, Pascale; Cattori, Valentino; Martínez, Fernando; Vargas, Astrid; Palomares, Francisco; López-Bao, José V; Simón, Miguel A; López, Guillermo; León-Vizcaino, Luis; Hofmann-Lehmann, Regina; Lutz, Hans

    2010-11-20

    Canine distemper virus (CDV) is a morbillivirus that is the etiological agent of one of the most important viral diseases affecting canids and an expanding range of other carnivores. Using real-time RT-PCR, CDV RNA was detected in organs of an Iberian lynx (Lynx pardinus) found dead in the Doñana National Park, Southwestern Andalusia, Spain. This finding may be of great importance for the conservation of the species; at present the Iberian lynx is the most critically endangered wild felid. The aim of the present study was to elucidate the significance of CDV for the Iberian lynx population. High viral loads were evident in the dead lynx, suggesting an etiological involvement of CDV in its death. When carnivores from the same region were analyzed by CDV RT-PCR, a stone marten (Martes foina) was positive. Phylogenetic analyses demonstrated high identity of the two detected CDVs and a close relationship to the European dog lineage of CDV. Antibodies to CDV were detected in 14.8% of 88 tested free-ranging Iberian lynxes. The sample seroprevalence was significantly higher in lynxes from the Doñana Natural Space (22.9%) than Sierra Morena (5%). The stone marten and a red fox (Vulpes vulpes) also tested seropositive. In conclusion, CDV is present in the Iberian lynx population, especially in the Doñana region, with sporadic cases of disease. To reduce the infectious pressure of CDV on this endangered population, a mass dog vaccination should be considered.

  6. Development and characterization of neutralizing monoclonal antibodies against canine distemper virus hemagglutinin protein.

    PubMed

    Bi, Zhenwei; Xia, Xingxia; Wang, Yongshan; Mei, Yongjie

    2015-04-01

    Canine distemper virus (CDV) causes a serious multisystemic disease in dogs and other carnivora. Hemagglutinin (H) protein-specific antibodies are mainly responsible for protective immunity against CDV infection. In the present study, six neutralizing MAbs to the H protein of CDV were newly obtained and characterized by immunizing BALB/c mice with a recent Chinese field isolate. Competitive binding inhibition assay revealed that they recognized four distinct antigenic regions of the H protein. Immunofluorescence assay and western blotting showed that all MAbs recognize the conformational rather than the linear epitopes of the H protein. Furthermore, in immunofluorescence and virus neutralization assays, two of the MAbs were found to react only with the recent Chinese field isolate and not with older CDV strains, including vaccine strain Onderstepoort, indicating there are neutralization-related antigenic variations between the recent Chinese field isolate and the older CDV strains examined in this study. The newly established MAbs are useful for differentiating the expanding CDV strains and could be used in immunotherapy and immunodiagnosis against infection with CDV.

  7. The anti-canine distemper virus activities of ex vivo-expanded canine natural killer cells.

    PubMed

    Park, Ji-Yun; Shin, Dong-Jun; Lee, Soo-Hyeon; Lee, Je-Jung; Suh, Guk-Hyun; Cho, Duck; Kim, Sang-Ki

    2015-04-17

    Natural killer (NK) cells play critical roles in induction of antiviral effects against various viruses of humans and animals. However, few data on NK cell activities during canine distemper virus (CDV) infections are available. Recently, we established a culture system allowing activation and expansion of canine non-B, non-T, large granular NK lymphocytes from PBMCs of normal dogs. In the present study, we explored the ability of such expanded NK cells to inhibit CDV infection in vitro. Cultured CD3-CD5-CD21- NK cells produced large amounts of IFN-γ, exhibited highly upregulated expression of mRNAs encoding NK-cell-associated receptors, and demonstrated strong natural killing activity against canine tumor cells. Although the expanded NK cells were dose-dependently cytotoxic to both normal and CDV-infected Vero cells, CDV infection rendered Vero cells more susceptible to NK cells. Pretreatment with anti-CDV serum from hyperimmunized dogs enhanced the antibody-dependent cellular cytotoxicity (ADCC) of NK cells against CDV-infected Vero cells. The culture supernatants of NK cells, added before or after infection, dose-dependently inhibited both CDV replication and development of CDV-induced cytopathic effects (CPEs) in Vero cells. Anti-IFN-γ antibody neutralized the inhibitory effects of NK cell culture supernatants on CDV replication and CPE induction in Vero cells. Such results emphasize the potential significance of NK cells in controlling CDV infection, and indicate that NK cells may play roles both during CDV infection and in combating such infections, under certain conditions.

  8. Canine distemper virus matrix protein influences particle infectivity, particle composition, and envelope distribution in polarized epithelial cells and modulates virulence.

    PubMed

    Dietzel, Erik; Anderson, Danielle E; Castan, Alexandre; von Messling, Veronika; Maisner, Andrea

    2011-07-01

    In paramyxoviruses, the matrix (M) protein mediates the interaction between the envelope and internal proteins during particle assembly and egress. In measles virus (MeV), M mutations, such as those found in subacute sclerosing panencephalitis (SSPE) strains, and differences in vaccine and wild-type M proteins can affect the strength of interaction with the envelope glycoproteins, assembly efficiency, and spread. However, the contribution of the M protein to the replication and pathogenesis of the closely related canine distemper virus (CDV) has not been characterized. To this end this, we generated a recombinant wild-type CDV carrying a vaccine strain M protein. The recombinant virus retained the parental growth phenotype in VerodogSLAMtag cells, but displayed an increased particle-to-infectivity ratio very similar to that of the vaccine strain, likely due to inefficient H protein incorporation. Even though infectious virus was released only from the apical surface, consistent with the release polarity of the wild-type CDV strain, envelope protein distribution in polarized epithelial cells reproduced the bipolar pattern seen in vaccine strain-infected cells. Most notably, the chimeric virus was completely attenuated in ferrets and caused only a mild and transient leukopenia, indicating that the differences in particle infectivity and envelope protein sorting mediated by the vaccine M protein contribute importantly to vaccine strain attenuation.

  9. Unusual Necrotizing Encephalitis in Raccoons and Skunks Concurrently Infected With Canine Distemper Virus and Sarcocystis sp.

    PubMed

    Kubiski, S V; Sisó, S; Church, M E; Cartoceti, A N; Barr, B; Pesavento, P A

    2016-05-01

    Canine distemper virus commonly infects free-ranging, terrestrial mesopredators throughout the United States. Due to the immunosuppressive effects of the virus, concurrent opportunistic infections are also common. Among these, secondary systemic protozoal infections have been described in a number of species. We report an unusual presentation of necrotizing encephalitis associated withSarcocystissp in four raccoons and one skunk concurrently infected with canine distemper virus. Lesions were characterized by variably sized necrotizing cavitations composed of abundant mineral admixed with inflammatory cells and protozoa.Sarcocystissp was confirmed via immunohistochemistry using a monoclonal antibody toSarcocystis neurona The pathologic changes are similar to lesions in human AIDS patients infected withToxoplasma gondii.

  10. A monoclonal antibody against truncated N protein (aa 277-471) of canine distemper virus.

    PubMed

    Yi, Li; Cheng, Shipeng

    2014-02-01

    Canine distemper (CD) is a highly contagious, systemic, viral disease of dogs seen worldwide. The nucleocapsid protein (NP) of canine distemper virus encloses virus assembly and has some regulatory functions in viral transcription and replication. Here, we describe a procedure to generate a monoclonal antibody (MAb) against CDV N protein and investigate its characteristics. Western blot analysis showed that the MAbs produced in this study were against CDV N specifically. Indirect immunofluorescence assay demonstrated that they could recognize native N protein in CDV-infected Vero cells. The MAbs reported here may provide valuable tools for the further exploration of biological properties and functions of N protein and may also be developed for potential clinical applications.

  11. Acute canine distemper encephalitis is associated with rapid neuronal loss and local immune activation.

    PubMed

    Rudd, Penny A; Bastien-Hamel, Louis-Etienne; von Messling, Veronika

    2010-04-01

    For most virus infections of the central nervous system (CNS), immune-mediated damage, the route of inoculation and death of infected cells all contribute to the pathology observed. To investigate the role of these factors in early canine distemper neuropathogenesis, we infected ferrets either intranasally or intraperitoneally with the neurovirulent canine distemper virus strain Snyder Hill. Regardless of the route of inoculation, the virus primarily targeted the olfactory bulb, brainstem, hippocampus and cerebellum, whereas only occasional foci were detected in the cortex. The infection led to widespread neuronal loss, which correlated with the clinical signs observed. Increased numbers of activated microglia, reactive gliosis and different pro-inflammatory cytokines were detected in the infected areas, suggesting that the presence and ultimate death of infected cells at early times after infection trigger strong local immune activation, despite the observed systemic immunosuppression.

  12. Distribution of 3beta-hydroxysteroid dehydrogenase in the cerebellum in canine distemper virus infection.

    PubMed

    Yarim, M; Kabakci, N

    2002-11-01

    The cerebella of eight dogs naturally infected with canine distemper virus (CDV) and two normal dogs were examined immunohistochemically for glial fibrillary acidic protein (GFAP) and 3beta-hydroxysteroid dehydrogenase (3beta-HSD). The clinical diagnosis of canine distemper was confirmed histopathologically and by the immunohistochemical demonstration of CDV antigen. In all dogs (healthy and infected), the Purkinje cells of the cerebellum were immunolabelled for 3beta-HSD activity. In infected dogs, 3beta-HSD labelling was prominent in astrocytes (particularly in areas of astrocytosis) whereas in healthy dogs such immunolabelling was weak. Double immunolabelling demonstrated that all GFAP-positive cells (especially in demyelinating areas) were also positive for 3beta-HSD. The results suggest that 3beta-HSD expression by astrocytes is associated with demyelination in CDV infection.

  13. Low Titers of Canine Distemper Virus Antibody in Wild Fishers (Martes pennanti) in the Eastern USA.

    PubMed

    Peper, Steven T; Peper, Randall L; Mitcheltree, Denise H; Kollias, George V; Brooks, Robert P; Stevens, Sadie S; Serfass, Thomas L

    2016-01-01

    Canine distemper virus (CDV) infects species in the order Carnivora. Members of the family Mustelidae are among the species most susceptible to CDV and have a high mortality rate after infection. Assessing an animal's pathogen or disease load prior to any reintroduction project is important to help protect the animal being reintroduced, as well as the wildlife and livestock in the area of relocation. We screened 58 fishers for CDV antibody prior to their release into Pennsylvania, US, as part of a reintroduction program. Five of the 58 (9%) fishers had a weak-positive reaction for CDV antibody at a dilution of 1:16. None of the fishers exhibited any clinical sign of canine distemper while being held prior to release.

  14. Antibodies to parvovirus, distemper virus and adenovirus conferred to household dogs using commercial combination vaccines containing Leptospira bacterin.

    PubMed

    Taguchi, M; Namikawa, K; Maruo, T; Lynch, J; Sahara, H

    2010-12-11

    To examine how the inclusion (+) or exclusion (-) of inactivated Leptospira antigens in a vaccine for canine parvovirus type 2 (CPV-2), canine distemper virus (CDV) and canine adenovirus type 2 (CAdV-2) affects antibody titres to CPV-2, CDV and CAdV-1 antigens, household dogs were vaccinated with commercially available vaccines from one of three manufacturers. CPV-2, CDV and CAdV-1 antibody titres were measured 11 to 13 months later and compared within three different age groups and three different bodyweight groups. There were significant differences between CPV-2 antibody titres in dogs vaccinated with (+) vaccine and those vaccinated with (-) vaccine for two products in the two-year-old group and for one product in the greater than seven-year-old group; no significant differences were seen that could be attributed to bodyweight. No differences in CDV antibody titres were observed within age groups, but a significant difference was seen in the 11 to 20 kg weight group for one product. Significant differences in CAdV-1 antibody titres were seen for one product in both the two-year-old group and the ≤10 kg weight group.

  15. Occurrence and geographical distribution of Canine Distemper Virus infection in red foxes (Vulpes vulpes) of Saxony-Anhalt, Germany.

    PubMed

    Denzin, N; Herwig, V; van der Grinten, E

    2013-02-22

    Canine Distemper Virus (CDV) infects dogs and a variety of carnivore species. In Saxony-Anhalt, a federal state of Germany, 761 foxes were examined for CDV infection, using real-time polymerase chain reaction (PCR), in the years 2010 and 2011. A prevalence of 30.5% was found for the whole time period without significant changes in prevalence between 2010 and 2011. The relative risk (RR) of a fox to test positive for CDV varied markedly within the area of the state and was significantly increased in some regions. The latter was confirmed by a spatial cluster test that identified a significant cluster (p<0.001) with a diameter of 44 km in the west of the state. To protect hounds and domestic dogs from CDV infection, vaccination is recommended in Saxony-Anhalt.

  16. Isolation and sequence analysis of a canine distemper virus from a raccoon dog in Jilin Province, China.

    PubMed

    Cheng, Yuening; Wang, Jianke; Zhang, Miao; Zhao, Jianjun; Shao, Xiqun; Ma, Zengjun; Zhao, Hang; Lin, Peng; Wu, Hua

    2015-10-01

    Canine distemper virus (CDV) is a major pathogen not only in raccoon dogs but also in a variety of carnivorous animals, including domesticated animals, particularly if they have not been vaccinated. In this study, a wild-type strain of CDV was isolated from lung tissue from a raccoon dog kept at a fur farm in Jilin Province, China. Cytopathic effects typical of CDV infection were observed after three blind passages in Vero cells, yielding a virus titer of 10(4.6) TCID50/mL. Virus identification was carried out by RT-PCR, immunofluorescence, electron microscopy, and genome sequencing. The results showed that the isolated virus, termed the SY strain, corresponded to the Asia-1 genotype of CDV and has a genome of 15,690 nucleotides. This represents the first complete nucleotide sequence of a CDV strain circulating in raccoon dogs in China.

  17. Rabies, canine distemper, and canine parvovirus exposure in large carnivore communities from two Zambian ecosystems.

    PubMed

    Berentsen, Are R; Dunbar, Mike R; Becker, Matthew S; M'soka, Jassiel; Droge, Egil; Sakuya, Nicholas M; Matandiko, Wigganson; McRobb, Rachel; Hanlon, Cathleen A

    2013-09-01

    Disease transmission within and among wild and domestic carnivores can have significant impacts on populations, particularly for threatened and endangered species. We used serology to evaluate potential exposure to rabies virus, canine distemper virus (CDV), and canine parvovirus (CPV) for populations of African lions (Panthera leo), African wild dogs (Lycaon pictus), and spotted hyenas (Crocuta crocuta) in Zambia's South Luangwa National Park (SLNP) and Liuwa Plain National Park (LPNP) as well as community lands bordering these areas. In addition, domestic dogs in the study region were evaluated for exposure to CDV and rabies. We provide the first comprehensive disease exposure data for these species in these ecosystems. Twenty-one lions, 20 hyenas, 13 wild dogs, and 38 domestic dogs were sampled across both regions from 2009 to 2011. Laboratory results show 10.5% of domestic dogs, 5.0% of hyenas, and 7.7% of wild dogs sampled were positive for CDV exposure. All lions were negative. Exposure to CPV was 10.0% and 4.8% for hyenas and lions, respectively. All wild dogs were negative, and domestic dogs were not tested due to insufficient serum samples. All species sampled were negative for rabies virus neutralizing antibodies except lions. Forty percent of lions tested positive for rabies virus neutralizing antibodies. Because these lions appeared clinically healthy, this finding is consistent with seroconversion following exposure to rabies antigen. To our knowledge, this finding represents the first ever documentation of rabies virus neutralizing antibodies consistent with rabies exposure that did not lead to clinical disease in free-ranging African lions from this region. With ever-increasing human pressure on these ecosystems, understanding disease transmission dynamics is essential for proper management and conservation of these carnivore species.

  18. The 2000 canine distemper epidemic in Caspian seals (Phoca caspica): pathology and analysis of contributory factors.

    PubMed

    Kuiken, T; Kennedy, S; Barrett, T; Van de Bildt, M W G; Borgsteede, F H; Brew, S D; Codd, G A; Duck, C; Deaville, R; Eybatov, T; Forsyth, M A; Foster, G; Jepson, P D; Kydyrmanov, A; Mitrofanov, I; Ward, C J; Wilson, S; Osterhaus, A D M E

    2006-05-01

    More than 10,000 Caspian seals (Phoca caspica) were reported dead in the Caspian Sea during spring and summer 2000. We performed necropsies and extensive laboratory analyses on 18 seals, as well as examination of the pattern of strandings and variation in weather in recent years, to identify the cause of mortality and potential contributory factors. The monthly stranding rate in 2000 was up to 2.8 times the historic mean. It was preceded by an unusually mild winter, as observed before in mass mortality events of pinnipeds. The primary diagnosis in 11 of 13 seals was canine distemper, characterized by broncho-interstitial pneumonia, lymphocytic necrosis and depletion in lymphoid organs, and the presence of typical intracytoplasmic inclusion bodies in multiple epithelia. Canine distemper virus infection was confirmed by phylogenetic analysis of reverse transcriptase-polymerase chain reaction products. Organochlorine and zinc concentrations in tissues of seals with canine distemper were comparable to those of Caspian seals in previous years. Concurrent bacterial infections that may have contributed to the mortality of the seals included Bordetella bronchiseptica (4/8 seals), Streptococcus phocae (3/8), Salmonella dublin (1/8), and S. choleraesuis (1/8). A newly identified bacterium, Corynebacterium caspium, was associated with balanoposthitis in one seal. Several infectious and parasitic organisms, including poxvirus, Atopobacter phocae, Eimeria- and Sarcocystis-like organisms, and Halarachne sp. were identified in Caspian seals for the first time.

  19. Antibody study in canine distemper virus nucleocapsid protein gene-immunized mice.

    PubMed

    Yuan, B; Li, X Y; Zhu, T; Yuan, L; Hu, J P; Chen, J; Gao, W; Ren, W Z

    2015-04-10

    The gene for the nucleocapsid (N) protein of canine distemper virus was cloned into the pMD-18T vector, and positive recombinant plasmids were obtained by enzyme digestion and sequencing. After digestion by both EcoRI and KpnI, the plasmid was directionally cloned into the eukaryotic expression vector pcDNA; the positive clone pcDNA-N was screened by electrophoresis and then transfected into COS-7 cells. Immunofluorescence analysis results showed that the canine distemper virus N protein was expressed in the cytoplasm of transfected COS-7 cells. After emulsification in Freund's adjuvant, the recombinant plasmid pcDNA-N was injected into the abdominal cavity of 8-week-old BABL/c mice, with the pcDNA original vector used as a negative control. Mice were immunized 3 times every 2 weeks. The blood of immunized mice was drawn 2 weeks after completing the immunizations to measure titer levels. The antibody titer in the pcDNA-N test was 10(1.62 ± 0.164), while in the control group this value was 10(0.52 ± 0.56), indicating that specific humoral immunity was induced in canine distemper virus nucleocapsid protein-immunized mice.

  20. Controversial results of therapy with mesenchymal stem cells in the acute phase of canine distemper disease.

    PubMed

    Pinheiro, A O; Cardoso, M T; Vidane, A S; Casals, J B; Passarelli, D; Alencar, A L F; Sousa, R L M; Fantinato-Neto, P; Oliveira, V C; Lara, V M; Ambrósio, C E

    2016-05-23

    Distemper disease is an infectious disease reported in several species of domestic and wild carnivores. The high mortality rate of animals infected with canine distemper virus (CDV) treated with currently available therapies has driven the study of new efficacious treatments. Mesenchymal stem cell (MSC)-based therapy is a promising therapeutic option for many degenerative, hereditary, and inflammatory diseases. Therefore, the aim of this study was to characterize stem cells derived from the canine fetal olfactory epithelium and to assess the systemic response of animals infected with CDV to symptomatic therapy and treatment with MSCs. Eight domestic mongrel dogs (N = 8) were divided into two groups: support group (SG) (N = 5) and support group + cell therapy (SGCT) (N = 3), which were monitored over 15 days. Blood samples were collected on days 0, 6, 9, 12, and 15 to assess blood count and serum biochemistry (urea, creatinine, alanine transferase, alkaline phosphatase, gamma-glutamyl transferase, total protein, albumin, and globulin), and urine samples were obtained on days 0 and 15 for urinary evaluation (urine I). The results showed a high mortality rate (SG = 4 and SGCT = 2), providing inadequate data on the clinical course of CDV infection. MSC therapy resulted in no significant improvement when administered during the acute phase of canine distemper disease, and a prevalence of animals with high mortality rate was found in both groups due to the severity of symptoms.

  1. First isolation and characterization of canine distemper virus in Vietnam with the immunohistochemical examination of the dog.

    PubMed

    Lan, Nguyen Thi; Yamaguchi, Ryoji; Kien, Tran Trung; Hirai, Takuya; Hidaka, Yuichi; Nam, Nguyen Huu

    2009-02-01

    Canine distemper caused by canine distemper virus (CDV) is a contagious, incurable, often fatal, multisystemic viral disease that affects the respiratory gastrointestinal and central nervous system. Strains Vn86 and Vn99 of CDV were isolated, we believe for the first time, in Vietnam from two 4-month-old autopsied dogs pathologically showing non-suppurative encephalitis with pneumonia, lymphoid depletion and severe gastroenteritis. These strains caused syncytium cytopathic effect in Vero cells and Vero cells expressing canine signaling lymphocyte activation molecules. The titers of cell-associated viruses of both strains were higher than for released viruses. Molecular analysis showed that both new isolates of CDV joined to the group of classic type that is far from the Asia 1 and Asia 2 groups. These results indicated that first isolation and characterization of canine distemper virus in Vietnam with the immunohistochemical examination of the dog.

  2. Forty years of canine vaccination.

    PubMed

    Appel, M J

    1999-01-01

    During the last 40 years vaccines have been developed that have greatly reduced the incidence of infectious diseases of dogs. In general, modified live products have been superior to inactivated vaccines for dogs. It can be expected that recombinant and/or DNA vaccines may dominate the market in the future. Although most vaccines on the market are safe and efficacious, there have been exceptions where disease was induced by vaccination or dogs were not protected. The failure of protection may in part be due to variations in individual vaccine batches. Only potency tests but not efficacy tests are required, which may not be sufficient. For example, a virus titer in a vaccine may be meaningless if the minimum protective dose is not known. Overattenuated virus (e.g., CDV-Ond or parvovirus in cat cells) may have a high titer in tissue culture but is not immunogenic. The question of frequency of vaccination of dogs should be addressed. Annual revaccinations for CDV, CPV, and CAV are probably not needed. However, it would be desirable to collect more data to support less frequent vaccinations. Annual immunization for bacterial diseases such as kennel cough, Lyme disease, and leptospirosis should continue. It also would be desirable to develop more oro/nasal vaccines, perhaps combined with newly developed vectors that are less likely to induce undesirable side effects that may be seen after parenteral vaccination. Finally a word of warning against homeopathic "nosodes" to replace tested canine vaccines. They will appear highly effective as long as the majority of dogs remain vaccinated. As soon as a nonvaccinated dog population is large enough to allow virulent agents to spread, disease outbreaks will occur and we will be back where we began 40 years ago.

  3. Construction of an expression system for bioactive IL-18 and generation of recombinant canine distemper virus expressing IL-18.

    PubMed

    Liu, Yuxiu; Sato, Hiroki; Hamana, Masahiro; Moonan, Navita Anisia; Yoneda, Misako; Xia, Xianzhu; Kai, Chieko

    2014-09-01

    Interleukin 18 (IL-18) plays an important role in the T-helper-cell type 1 immune response against intracellular parasites, bacteria and viral infections. It has been widely used as an adjuvant for vaccines and as an anticancer agent. However, IL-18 protein lacks a typical signal sequence and requires cleavage into its mature active form by caspase 1. In this study, we constructed mammalian expression vectors carrying cDNA encoding mature canine IL-18 (cIL-18) or mouse IL-18 (mIL-18) fused to the human IL-2 (hIL-2) signal sequence. The expressed proIL-18 proteins were processed to their mature forms in the cells. The supernatants of cells transfected with these plasmids induced high interferon-γ production in canine peripheral blood mononuclear cells or mouse splenocytes, respectively, indicating the secretion of bioactive IL-18. Using reverse genetics, we also generated a recombinant canine distemper virus that expresses cIL-18 or mIL-18 fused to the hIL-2 signal sequence. As expected, both recombinant viruses produced mature IL-18 in the infected cells, which secreted bioactive IL-18. These results indicate that the signal sequence from hIL-2 is suitable for the secretion of mature IL-18. These recombinant viruses can also potentially be used as immunoadjuvants and agents for anticancer therapies in vivo.

  4. Experiments with a homologous, inactivated canine parvovirus vaccine in vaccination programmers for dogs.

    PubMed

    Wilson, J H; Hermann-Dekkers, W M

    1982-01-01

    The significance of canine parvovirus (CPV) infections as a permanent threat susceptible dogs, in particular pups, made the authors develop three liquid homologous inactivated adjuvant CPV vaccines that were compatible with existing canine vaccines and could be incorporated in current vaccination programmes. On vaccine (Kavak Parvo) contained only the CPV component, the second product (Kavak i-LP) also contained two inactivated leptospiral antigens, and the third vaccine (Kavak i-HLP) contained in addition an inactivated canine hepatitis virus. This paper reports on the studies conducted to test the safety and efficacy of the three products. They were used as such and as diluents for freeze dried vaccines containing live attenuated measles, distemper, and hepatitis viruses. The study was performed in a breeding kennel where all dogs were free from CPV antibodies and the nonvaccinated sentinels remained so for the course of the study. All vaccines proved to be safe in dogs of all ages, including pregnant bitches. The efficacy of the CPV component was studied both by monitoring antibody titres for more than a year and by challenge exposure of some dogs to virulent CPV. The results obtained from these studies prove that the CPV component used in the three vaccines can be incorporated as indicated in the recommended canine vaccination programmes. The observations that the inactivated CPV and hepatitis components do induce an active immunity in pups that are still protected by low levels of maternally derived antibodies against these viruses, make those vaccines very suitable in breeding kennels. Additional studies on a comparative basis are being continued in edemically CPV infected breeding kennels to quantify the significance of these observations in these special conditions.

  5. Detection by hemi-nested reverse transcription polymerase chain reaction and genetic characterization of wild type strains of Canine distemper virus in suspected infected dogs.

    PubMed

    Di Francesco, Cristina E; Di Francesco, Daniela; Di Martino, Barbara; Speranza, Roberto; Santori, Domenico; Boari, Andrea; Marsilio, Fulvio

    2012-01-01

    A new highly sensitive and specific hemi-nested reverse transcription polymerase chain reaction (RT-PCR) assay was applied to detect nucleoprotein (NP) gene of Canine distemper virus (CDV) in samples collected from dogs showing respiratory, gastrointestinal, and neurological signs. Thirty-eight out of 86 samples were positive suggesting that despite the vaccination, canine distemper may still represent a high risk to the canine population. The 968 base pair (bp) fragments from the hemagglutinin (H) gene of 10 viral strains detected in positive samples were amplified and analyzed by restriction fragment length polymorphism (RFLP) using AluI and PsiI enzymes in order to differentiate among vaccine and wild-type CDV strains and to characterize the field viral strains. The products of the both enzymatic digestions allowed identification all viruses as wild strains of CDV. In addition, the RFLP analysis with AluI provided additional information about the identity level among the strains analyzed on the basis of the positions of the cleavage site in the nucleotide sequences of the H gene. The method could be a more useful and simpler method for molecular studies of CDV strains.

  6. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Type 2 Vaccine. 113.305 Section 113.305 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... STANDARD REQUIREMENTS Live Virus Vaccines § 113.305 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine. Canine Hepatitis Vaccine and Canine Adenovirus Type 2 Vaccine shall be prepared from virus-bearing...

  7. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Type 2 Vaccine. 113.305 Section 113.305 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... STANDARD REQUIREMENTS Live Virus Vaccines § 113.305 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine. Canine Hepatitis Vaccine and Canine Adenovirus Type 2 Vaccine shall be prepared from virus-bearing...

  8. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Type 2 Vaccine. 113.305 Section 113.305 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... STANDARD REQUIREMENTS Live Virus Vaccines § 113.305 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine. Canine Hepatitis Vaccine and Canine Adenovirus Type 2 Vaccine shall be prepared from virus-bearing...

  9. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Type 2 Vaccine. 113.305 Section 113.305 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... STANDARD REQUIREMENTS Live Virus Vaccines § 113.305 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine. Canine Hepatitis Vaccine and Canine Adenovirus Type 2 Vaccine shall be prepared from virus-bearing...

  10. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Type 2 Vaccine. 113.305 Section 113.305 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... STANDARD REQUIREMENTS Live Virus Vaccines § 113.305 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine. Canine Hepatitis Vaccine and Canine Adenovirus Type 2 Vaccine shall be prepared from virus-bearing...

  11. RT-PCR and sequence analysis of the full-length fusion protein of Canine Distemper Virus from domestic dogs.

    PubMed

    Romanutti, Carina; Gallo Calderón, Marina; Keller, Leticia; Mattion, Nora; La Torre, José

    2016-02-01

    During 2007-2014, 84 out of 236 (35.6%) samples from domestic dogs submitted to our laboratory for diagnostic purposes were positive for Canine Distemper Virus (CDV), as analyzed by RT-PCR amplification of a fragment of the nucleoprotein gene. Fifty-nine of them (70.2%) were from dogs that had been vaccinated against CDV. The full-length gene encoding the Fusion (F) protein of fifteen isolates was sequenced and compared with that of those of other CDVs, including wild-type and vaccine strains. Phylogenetic analysis using the F gene full-length sequences grouped all the Argentinean CDV strains in the SA2 clade. Sequence identity with the Onderstepoort vaccine strain was 89.0-90.6%, and the highest divergence was found in the 135 amino acids corresponding to the F protein signal-peptide, Fsp (64.4-66.7% identity). In contrast, this region was highly conserved among the local strains (94.1-100% identity). One extra putative N-glycosylation site was identified in the F gene of CDV Argentinean strains with respect to the vaccine strain. The present report is the first to analyze full-length F protein sequences of CDV strains circulating in Argentina, and contributes to the knowledge of molecular epidemiology of CDV, which may help in understanding future disease outbreaks.

  12. Duration of Maternal Antibodies against Canine Distemper Virus and Hendra Virus in Pteropid Bats.

    PubMed

    Epstein, Jonathan H; Baker, Michelle L; Zambrana-Torrelio, Carlos; Middleton, Deborah; Barr, Jennifer A; Dubovi, Edward; Boyd, Victoria; Pope, Brian; Todd, Shawn; Crameri, Gary; Walsh, Allyson; Pelican, Katey; Fielder, Mark D; Davies, Angela J; Wang, Lin-Fa; Daszak, Peter

    2013-01-01

    Old World frugivorous bats have been identified as natural hosts for emerging zoonotic viruses of significant public health concern, including henipaviruses (Nipah and Hendra virus), Ebola virus, and Marburg virus. Epidemiological studies of these viruses in bats often utilize serology to describe viral dynamics, with particular attention paid to juveniles, whose birth increases the overall susceptibility of the population to a viral outbreak once maternal immunity wanes. However, little is understood about bat immunology, including the duration of maternal antibodies in neonates. Understanding duration of maternally derived immunity is critical for characterizing viral dynamics in bat populations, which may help assess the risk of spillover to humans. We conducted two separate studies of pregnant Pteropus bat species and their offspring to measure the half-life and duration of antibodies to 1) canine distemper virus antigen in vaccinated captive Pteropus hypomelanus; and 2) Hendra virus in wild-caught, naturally infected Pteropus alecto. Both of these pteropid bat species are known reservoirs for henipaviruses. We found that in both species, antibodies were transferred from dam to pup. In P. hypomelanus pups, titers against CDV waned over a mean period of 228.6 days (95% CI: 185.4-271.8) and had a mean terminal phase half-life of 96.0 days (CI 95%: 30.7-299.7). In P. alecto pups, antibodies waned over 255.13 days (95% CI: 221.0-289.3) and had a mean terminal phase half-life of 52.24 days (CI 95%: 33.76-80.83). Each species showed a duration of transferred maternal immunity of between 7.5 and 8.5 months, which was longer than has been previously estimated. These data will allow for more accurate interpretation of age-related Henipavirus serological data collected from wild pteropid bats.

  13. Pathogenesis of canine distemper virus in experimentally infected raccoon dogs, foxes, and minks.

    PubMed

    Zhao, Jianjun; Shi, Ning; Sun, Yangang; Martella, Vito; Nikolin, Veljko; Zhu, Chunsheng; Zhang, Hailing; Hu, Bo; Bai, Xue; Yan, Xijun

    2015-10-01

    Canine distemper virus (CDV) infects a broad range of carnivores and causes a highly contagious disease with severe immunosuppression. The disease severity markedly varies in different species. To investigate the pathogenesis of CDV in raccoon dog (Nyctereutes procyonoides), fox (Vulpes vulpes) and mink (Neovison vison) species, three groups of CDV sero-negative animals were infected with CDV strain LN(10)1. This CDV strain belongs to the Asia-1 genotype, which is epidemiologically predominant in carnivores in China. CDV infection provoked marked differences in virulence in the three species that were studied. Raccoon dogs developed fever, severe conjunctivitis, and pathological lesions, with 100% (5/5) mortality and with high viral RNA loads in organs within 15 days post infection (dpi). In infected foxes, the onset of the disease was delayed, with 40% (2/5) mortality by 21 dpi. Infected minks developed only mild clinical signs and pathological lesions, and mortality was not observed. Raccoon dogs and foxes showed more severe immune suppression (lymphopenia, decreased lymphocyte proliferation, viremia and low-level virus neutralizing antibodies) than minks. We also observed a distinct pattern of cytokine mRNA transcripts at different times after infection. Decreased IFN-γ and IL-4 mRNA responses were evident in the animals with fatal disease, while up-regulation of these cytokines was observed in the animals surviving the infection. Increased TNF-α response was detected in animals with mild or severe clinical signs. Based on the results, we could distinguish three different patterns of disease after experimental CDV infection, e.g. a mild form in minks, a moderate form in foxes and a severe disease in raccoon dogs. The observed differences in susceptibility to CDV could be related to distinct host cytokine profiles. Comparative evaluation of CDV pathogenesis in various animal species is pivotal to generate models suitable for the evaluation of CDV

  14. Detection of canine distemper virus serum neutralizing antibodies in captive U.S. phocids.

    PubMed

    Clancy, Meredith M; Gamble, Kathryn C; Travis, Dominic A

    2013-03-01

    Antibodies to morbilliviruses have been documented in free-ranging pinnipeds throughout populations in the Atlantic and Arctic Oceans, but not from the Pacific Ocean. As a symbolic geographic barrier between the exposed Atlantic and naive Pacific populations, the captive phocid population in North America had undocumented serologic status. In this study, canine distemper virus (CDV) serum neutralization assays were used to assess the prevalence of antibodies in this population with participation of 25 U.S. institutions from grey seals (Halichoerus grypus, n = 6) and harbor seals (Phoca vitulina, n = 108). Historic and environmental risk factors associated with the epidemiology of distemper virus were collected by survey. Based on antibodies to canine distemper virus, the prevalence of exposure in this population was 25.5%, with 28 seals (grey, n = 2; harbor, n = 26) demonstrating antibody titers > or = 1:16, and positive titers ranged from 1:4 to 1:1,536. By survey analysis, strong associations with seropositive status were identified for captive origin (P = 0.013) and movement among institutions (P = 0.024). Size of population has positive correlation with likelihood of seropositive seals at an institution (P = 0.020). However, no major husbandry or enclosure-based risk factors were identified in institutions with seropositive seals, and no interaction between individual or institutional risk factors was identified. Previously undocumented prior to this study, CDV antibodies were measured in harbor seals (n = 2) recently stranded from the Pacific coast.

  15. Cloning and characterization of DNA complementary to the canine distemper virus mRNA encoding matrix, phosphoprotein, and nucleocapsid protein

    SciTech Connect

    Rozenblatt, S.; Eizenberg, O.; Englund, G.; Bellini, W.J.

    1985-02-01

    Double-stranded cDNA synthesized from total polyadenylate-containing mRNA, extracted from monkey kidney cells infected with canine distemper virus (CDV), has been cloned into the PstI site of Escherichia coli plasmid pBR322. Clones containing canine distemper virus DNA were identified by hybridization to a canine distemper virus-specific, /sup 32/P-labeled cDNA. Four specific clones containing different classes of sequences have been identified. The cloned plasmids contain inserts of 800 (clone 44-80), 960 (clone 74-16), 1700 (clone 364), and 950 (clone 40-9) base pairs. The sizes of the mRNA species complementary to these inserts are 1500, 1850, 1850 and 2500 nucleotides, respectively, as determined by the Northern technique. Three of the cloned DNA fragments were further identified as the reverse transcripts of the mRNA coding for the matrix, phosphoprotein, and nucleocapsid protein of CDV.

  16. Phylogenetic analysis of canine distemper virus in South America clade 1 reveals unique molecular signatures of the local epidemic.

    PubMed

    Fischer, Cristine D B; Gräf, Tiago; Ikuta, Nilo; Lehmann, Fernanda K M; Passos, Daniel T; Makiejczuk, Aline; Silveira, Marcos A T; Fonseca, André S K; Canal, Cláudio W; Lunge, Vagner R

    2016-07-01

    Canine distemper virus (CDV) is a highly contagious pathogen for domestic dogs and several wild carnivore species. In Brazil, natural infection of CDV in dogs is very high due to the large non-vaccinated dog population, a scenario that calls for new studies on the molecular epidemiology. This study investigates the phylodynamics and amino-acid signatures of CDV epidemic in South America by analyzing a large dataset compiled from publicly available sequences and also by collecting new samples from Brazil. A population of 175 dogs with canine distemper (CD) signs was sampled, from which 89 were positive for CDV, generating 42 new CDV sequences. Phylogenetic analysis of the new and publicly available sequences revealed that Brazilian sequences mainly clustered in South America 1 (SA1) clade, which has its origin estimated to the late 1980's. The reconstruction of the demographic history in SA1 clade showed an epidemic expanding until the recent years, doubling in size every nine years. SA1 clade epidemic distinguished from the world CDV epidemic by the emergence of the R580Q strain, a very rare and potentially detrimental substitution in the viral genome. The R580Q substitution was estimated to have happened in one single evolutionary step in the epidemic history in SA1 clade, emerging shortly after introduction to the continent. Moreover, a high prevalence (11.9%) of the Y549H mutation was observed among the domestic dogs sampled here. This finding was associated (p<0.05) with outcome-death and higher frequency in mixed-breed dogs, the later being an indicator of a continuous exchange of CDV strains circulating among wild carnivores and domestic dogs. The results reported here highlight the diversity of the worldwide CDV epidemic and reveal local features that can be valuable for combating the disease.

  17. Canine adenovirus based rabies vaccines.

    PubMed

    Tordo, N; Foumier, A; Jallet, C; Szelechowski, M; Klonjkowski, B; Eloit, M

    2008-01-01

    Adenovirus based vectors are very attractive candidates for vaccination purposes as they induce in mammalian hosts potent humoral, mucosal and cellular immune responses to antigens encoded by the inserted genes. We have generated E1-deleted and replication-competent recombinant canine type-2 adenoviruses expressing the rabies virus glycoprotein (G). The effectiveness of both vectors to express a native G protein has been characterized in vitro in permissive cell lines. We compared the humoral and cellular immune responses induced in mice by intramuscular injection of the recombinant canine adenovirus vectors with those induced by a human (Ad5) E1-deleted virus expressing the same rabies G protein. Humoral responses specific to the adenoviruses or the rabies glycoprotein antigens were studied. The influence of the mouse strain was observed using replication-competent canine adenovirus. A high level of rabies neutralizing antibody was observed upon i.m. inoculation, and 100% of mice survived lethal challenge. These results are very promising in the perspective of oral vaccine for dog rabies control.

  18. Canine viral vaccines at a turning point--a personal perspective.

    PubMed

    Carmichael, L E

    1999-01-01

    The most important canine viral infections are distemper and CPV-2. Problems of variable CD vaccine safety and efficacy persist, but CD vaccines have greatly reduced the prevalence of disease and cases in vaccinated dogs are now rare. Canine hepatitis (ICH, CAV-1 infection) also has been controlled well by vaccines for more than 35 years and it is now rare; the sporadic cases seen in the 1990s have usually occurred in unvaccinated dogs. CAV-2 vaccines should, therefore, continue to be given since they have proved to be safe and effective, and prevent hepatitis as well as adenoviral tracheobronchitis. Failure to vaccinate would likely result in increase in cases of ICH, a serious disease, but never as significant as distemper and CPV infection. "Are we vaccinating too often?" The question is complex, but the dominant opinion is "yes" (Smith, 1995). The question cannot be responded to unequivocally, however, since manufacturers employ different strains that vary in their immunizing capacity and, probably, duration of immunity. This question was frequent with distemper in the 1960s. At that time, many veterinarians tested batches of the vaccine they used by providing pre- and postvaccinal sera to competent diagnostic laboratories. That practice appeared to benefit veterinarians and dogs, as well as the quality of vaccines. Unfortunately, many owners and some veterinarians seem to hold the view that infectious diseases such as parvovirus infection can be controlled by frequent vaccination alone. The common practice of dog breeders of vaccinating their animals several times each year is senseless. Revaccination for distemper and parvovirus infection is suggested at 1 year of age, but recommendations regarding the frequency of most vaccinations given after that time are unclear. Since most distemper and CPV-2 vaccines probably provide immunity that endures several years, vaccination at 3- to 5-year intervals, after the first year, seems a reasonable practice until more

  19. 9 CFR 113.316 - Canine Parainfluenza Vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Canine Parainfluenza Vaccine. 113.316... Virus Vaccines § 113.316 Canine Parainfluenza Vaccine. Canine Parainfluenza Vaccine shall be prepared... immunogenic shall be used for preparing seeds for vaccine production. All serials of vaccine shall be...

  20. 9 CFR 113.316 - Canine Parainfluenza Vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Canine Parainfluenza Vaccine. 113.316... Virus Vaccines § 113.316 Canine Parainfluenza Vaccine. Canine Parainfluenza Vaccine shall be prepared... immunogenic shall be used for preparing seeds for vaccine production. All serials of vaccine shall be...

  1. 9 CFR 113.316 - Canine Parainfluenza Vaccine.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Canine Parainfluenza Vaccine. 113.316... Virus Vaccines § 113.316 Canine Parainfluenza Vaccine. Canine Parainfluenza Vaccine shall be prepared... immunogenic shall be used for preparing seeds for vaccine production. All serials of vaccine shall be...

  2. 9 CFR 113.316 - Canine Parainfluenza Vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Canine Parainfluenza Vaccine. 113.316... Virus Vaccines § 113.316 Canine Parainfluenza Vaccine. Canine Parainfluenza Vaccine shall be prepared... immunogenic shall be used for preparing seeds for vaccine production. All serials of vaccine shall be...

  3. 9 CFR 113.316 - Canine Parainfluenza Vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Canine Parainfluenza Vaccine. 113.316... Virus Vaccines § 113.316 Canine Parainfluenza Vaccine. Canine Parainfluenza Vaccine shall be prepared... immunogenic shall be used for preparing seeds for vaccine production. All serials of vaccine shall be...

  4. 9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Type 2 Vaccine, Killed Virus. 113.202 Section 113.202 Animals and Animal Products ANIMAL AND PLANT...; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.202 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed...

  5. 9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Type 2 Vaccine, Killed Virus. 113.202 Section 113.202 Animals and Animal Products ANIMAL AND PLANT...; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.202 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed...

  6. 9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Type 2 Vaccine, Killed Virus. 113.202 Section 113.202 Animals and Animal Products ANIMAL AND PLANT...; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.202 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed...

  7. 9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Type 2 Vaccine, Killed Virus. 113.202 Section 113.202 Animals and Animal Products ANIMAL AND PLANT...; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.202 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed...

  8. 9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Type 2 Vaccine, Killed Virus. 113.202 Section 113.202 Animals and Animal Products ANIMAL AND PLANT...; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.202 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed...

  9. Non-cytocidal infection of keratinocytes by canine distemper virus in the so-called hard pad disease of canine distemper.

    PubMed

    Gröne, A; Groeters, S; Koutinas, A; Saridomichelakis, M; Baumgärtner, W

    2003-10-17

    A late, but not uncommon sequel to canine distemper virus (CDV) infection of dogs is thickening of footpads and nasal planum, the so-called hard pad disease, originally described as vacuolar degeneration of epidermal keratinocytes with inclusion body formation and massive hyperkeratosis. However, in a recent study of footpads of naturally CDV-infected dogs only hyperkeratosis was observed without any of the other changes. Instead, acanthosis was frequently noticed. CDV nucleoprotein was present in the suprabasal keratinocytes and eccrine epithelial glands only. No CDV nucleoprotein was present in basal keratinocytes. This observation in combination with lack of obvious cytocidal changes strongly suggested the possibility of a restricted viral infection with presence of viral mRNA but without protein expression. Therefore, the presence of CDV nucleoprotein mRNA was investigated using in situ hybridization and compared to the localization of the nucleoprotein in footpads of clinically healthy and distemper dogs. Viral nucleoprotein and nucleoprotein mRNA in nearly all cases co-localized to the same compartments and basal keratinocytes did not contain nucleoprotein mRNA. These findings dispute the idea of a restricted viral infection of footpad keratinocytes in dogs with natural CDV infection. Instead, a migration of the virus to the epidermal surface along with the proliferating and differentiating epithelium is the most likely explanation for the lack of virus antigen in basal keratinocytes.

  10. Identification, expression and antigenic analysis of recombinant hemagglutinin proteins of canine distemper virus.

    PubMed

    Chan, Kun-Wei; Hsieh, Hsien-Hua; Wang, Hsien-Chi; Lee, Ya-Jane; Sung, Ming-Hua; Wong, Min-Liang; Hsu, Wei-Li

    2009-01-01

    Canine distemper (CD) is a widely distributed disease of dogs, caused by the canine distemper virus (CDV). In the present study, the gene encoding the hemagglutinin (H) protein of a CDV isolate from central Taiwan was sequenced and compared with other strains. Sequence variations were noticed in the H gene from the field CDV strain that had previously been implicated in the increasing incidence of CD. To establish a serology-based diagnostic test, the full-length H protein, as well as five deletion mutants of a recombinant H protein of the local isolate, were produced using an E. coli expression system. Three truncated recombinant proteins with relatively high expression levels, designated HM3, HM4 and HM5, were used as antigens to examine their reactivity with canine sera. By using three negative sera and 17 CD-positive sera, the high specificity of recombinant H proteins was observed by ELISA. In addition, immunoblotting demonstrated that all three purified recombinant proteins exhibit an antigenic property recognized by the serum of a CD-suspected dog.

  11. In-vitro antiviral efficacy of ribavirin and interferon-alpha against canine distemper virus.

    PubMed

    Carvalho, Otávio V; Saraiva, Giuliana L; Ferreira, Caroline G T; Felix, Daniele M; Fietto, Juliana L R; Bressan, Gustavo C; Almeida, Márcia R; Silva Júnior, Abelardo

    2014-10-01

    Canine distemper is a highly contagious disease with high incidence and lethality in the canine population. The objective of this study was to evaluate the efficacy of antiviral action with ribavirin (RBV), interferon-alpha (IFNα), and combinations of RBV and IFNα against canine distemper virus (CDV). Vero cells inoculated with CDV were treated with RBV, IFNα, and combinations of these drugs. The efficacy to inhibit viral replication was evaluated by adding the compounds at different times to determine which step of the viral replicative process was affected. Both drugs were effective against CDV in vitro. The IFNα was the most active compound, with an average IC50 (50% inhibitory concentration) value lower than the IC50 of the RBV. Ribavirin (RBV) was more selective than IFNα, however, and neither drug showed extracellular antiviral activity. The combination of RBV and IFNα exhibited antiviral activity for the intra- and extracellular stages of the replicative cycle of CDV, although the intracellular viral inhibition was higher. Both RBV and IFNα showed high antiviral efficacy against CDV, and furthermore, RBV + IFNα combinations have shown greater interference range in viral infectivity. These compounds could potentially be used to treat clinical disease associated with CDV infection.

  12. Dog overpopulation and burden of exposure to canine distemper virus and other pathogens on Santa Cruz Island, Galapagos.

    PubMed

    Diaz, Nicole M; Mendez, Gabriella S; Grijalva, C Jaime; Walden, Heather S; Cruz, Marilyn; Aragon, Eduardo; Hernandez, Jorge A

    2016-01-01

    Dog overpopulation and diseases are hazards to native island species and humans on the Galapagos. Vaccination and importation of dogs are prohibited on the Galapagos. Risk management of these hazards requires the use of science-based risk assessment and risk communication. The objectives of the study reported here were (i) to estimate the human:dog ratio and (ii) the prevalence of and identify exposure factors associated with positive antibody titers to canine distemper virus (CDV) and other pathogens, as well as infection with intestinal parasites in owned dogs on Santa Cruz Island, Galapagos in September 2014. The observed human:dog ratio was 6.148:1 which extrapolates to 2503 dogs (two times more than a recent dog count conducted by Galapagos Biosecurity Agency in March 2014). The proportion of spayed female dogs (50%) was higher, compared to neutered male dogs (30%) (p=0.04). Prevalence of dogs with positive antibody titers to CDV was 36% (95% CI=26, 46%), to canine parvovirus was 89% (95% CI=82, 95%), and to canine adenovirus was 40% (95% CI=30, 51%). The frequency of seropositive dogs to CDV was lower in urban dogs (26%), compared to rural dogs (53%) (p<0.05). A positive interaction effect between rural residence and spay/neuter status on seropositivity to CDV was observed, which we discuss in this report. Because vaccination is prohibited, the dog population on Santa Cruz is susceptible to an outbreak of CDV (particularly among urban dogs) with potential spill over to marine mammals. Dog's age (1-2 or 3-14 years old, compared to younger dogs), and residence (rural, urban) were associated with positive antibody titers to parvovirus, adenovirus, Ehrlichia spp., or Anaplasma spp., as well as infection with Ancylostoma spp., an intestinal parasite in dogs that can be transmitted to humans, particularly children. These results provide the most comprehensive assessment of dog overpopulation and exposure to CDV and other pathogens on the Galapagos to date.

  13. Up-regulation of the hyaluronate receptor CD44 in canine distemper demyelinated plaques.

    PubMed

    Alldinger, S; Fonfara, S; Kremmer, E; Baumgärtner, W

    2000-02-01

    CD44 antigen (CD44), the principle cell surface receptor for hyaluronate, is up-regulated in the human demyelinating disease multiple sclerosis on fibrous astrocytes. As astrocytes are the main target cell of canine distemper virus (CDV), the consequences of a CDV infection on the CD44 expression and distribution in brains with spontaneous demyelinating canine distemper encephalitis (CDE) were of interest. Thirteen acute, 35 subacute, and 11 chronic plaques of nine dogs with immunohistologically confirmed CDE and brains of control dogs were included in the study. For light microscopy, 5-micron-thick serial sections were stained with H&E and incubated with monoclonal antibodies (mAbs) against CD44 and canine distemper virus nucleoprotein and polyclonal antibodies (pAbs) against glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP). For immunoelectron microscopy, 90-nm-thick sections were double stained with anti-GFAP and anti-CD44 mAbs to specify CD44-expressing structures. In controls, CD44 was diffusely distributed in the white matter and single meningeal cells exhibited a marginal expression of the antigen. In acute and more prominently in subacute demyelinating encephalitis, there was a plaque-associated up-regulation of CD44 which paralleled GFAP. In chronic demyelinating lesions, a reduction of CD44 associated with a loss of GFAP-positive astrocytes was noted. Additionally, in chronic plaques, CD44 was expressed on the cell membrane of perivascular mononuclear cells. Immunoelectron microscopically, in controls, CD44 was rarely demonstrated on astrocytic cell processes. In contrast, in brains with CDE CD44 was found on the cell membrane of broadened astrocytic cell processes. In summary, CD44 is up-regulated on astrocytes in the early phase of CDE and seems to represent a marker for the activation of immune cells in the late phase of the infection.

  14. Canine distemper virus induces apoptosis in cervical tumor derived cell lines.

    PubMed

    Del Puerto, Helen L; Martins, Almir S; Milsted, Amy; Souza-Fagundes, Elaine M; Braz, Gissandra F; Hissa, Barbara; Andrade, Luciana O; Alves, Fabiana; Rajão, Daniela S; Leite, Rômulo C; Vasconcelos, Anilton C

    2011-06-30

    Apoptosis can be induced or inhibited by viral proteins, it can form part of the host defense against virus infection, or it can be a mechanism for viral spread to neighboring cells. Canine distemper virus (CDV) induces apoptotic cells in lymphoid tissues and in the cerebellum of dogs naturally infected. CDV also produces a cytopathologic effect, leading to apoptosis in Vero cells in tissue culture. We tested canine distemper virus, a member of the Paramyxoviridae family, for the ability to trigger apoptosis in HeLa cells, derived from cervical cancer cells resistant to apoptosis. To study the effect of CDV infection in HeLa cells, we examined apoptotic markers 24 h post infection (pi), by flow cytometry assay for DNA fragmentation, real-time PCR assay for caspase-3 and caspase-8 mRNA expression, and by caspase-3 and -8 immunocytochemistry. Flow cytometry showed that DNA fragmentation was induced in HeLa cells infected by CDV, and immunocytochemistry revealed a significant increase in the levels of the cleaved active form of caspase-3 protein, but did not show any difference in expression of caspase-8, indicating an intrinsic apoptotic pathway. Confirming this observation, expression of caspase-3 mRNA was higher in CDV infected HeLa cells than control cells; however, there was no statistically significant change in caspase-8 mRNA expression profile. Our data suggest that canine distemper virus induced apoptosis in HeLa cells, triggering apoptosis by the intrinsic pathway, with no participation of the initiator caspase -8 from the extrinsic pathway. In conclusion, the cellular stress caused by CDV infection of HeLa cells, leading to apoptosis, can be used as a tool in future research for cervical cancer treatment and control.

  15. First report of clinical disease associated with canine distemper virus infection in a wild black bear (Ursus americana).

    PubMed

    Cottrell, W O; Keel, M Kevin; Brooks, J W; Mead, D G; Phillips, J E

    2013-10-01

    An approximately 1-yr-old black bear was discovered on the porch of a rural residence in southwestern Pennsylvania on October 26, 2011, where it remained during the day in spite of efforts to frighten it away. The bear exhibited periods of somnolence and sporadic tremors and seizures. It was euthanized by gunshot that evening. Immediately after euthanasia it was observed to have footpads that exuded fluid when compressed. It was submitted for necropsy the next day where roughened footpads were noted. Histologic examination of the brain demonstrated nonsuppurative encephalitis with eosinophilic intranuclear and intracytoplasmic inclusion bodies in neurons. The footpads were thickened and hyperkeratotic. Canine distemper virus (CDV) was detected by immunohistochemistry (IHC) in the brain and footpads, and by reverse transcription polymerase chain reaction (RT-PCR) from the brain tissue. Phylogenetic analysis indicated that the CDV cDNA from the bear had 98.2% nucleotide identity to the Rockborn-Candur vaccine and a canine isolate from 2004 in Missouri, USA, and 97.3% nucleotide identity to a raccoon CDV isolated in 2011 from Tennessee, USA. This represents a first report of CDV as a cause of encephalitis or footpad hyperkeratosis in a wild black bear.

  16. The fusion protein of wild-type canine distemper virus is a major determinant of persistent infection.

    PubMed

    Plattet, Philippe; Rivals, Jean-Paul; Zuber, Benoît; Brunner, Jean-Marc; Zurbriggen, Andreas; Wittek, Riccardo

    2005-07-05

    The wild-type A75/17 canine distemper virus (CDV) strain induces a persistent infection in the central nervous system but infects cell lines very inefficiently. In contrast, the genetically more distant Onderstepoort CDV vaccine strain (OP-CDV) induces extensive syncytia formation. Here, we investigated the roles of wild-type fusion (F(WT)) and attachment (H(WT)) proteins in Vero cells expressing, or not, the canine SLAM receptor by transfection experiments and by studying recombinants viruses expressing different combinations of wild-type and OP-CDV glycoproteins. We show that low fusogenicity is not due to a defect of the envelope proteins to reach the cell surface and that H(WT) determines persistent infection in a receptor-dependent manner, emphasizing the role of SLAM as a potent enhancer of fusogenicity. However, importantly, F(WT) reduced cell-to-cell fusion independently of the cell surface receptor, thus demonstrating that the fusion protein of the neurovirulent A75/17-CDV strain plays a key role in determining persistent infection.

  17. The fusion protein of wild-type canine distemper virus is a major determinant of persistent infection

    SciTech Connect

    Plattet, Philippe; Rivals, Jean-Paul; Zuber, BenoIt; Brunner, Jean-Marc; Zurbriggen, Andreas; Wittek, Riccardo . E-mail: Riccardo.Wittek@unil.ch

    2005-07-05

    The wild-type A75/17 canine distemper virus (CDV) strain induces a persistent infection in the central nervous system but infects cell lines very inefficiently. In contrast, the genetically more distant Onderstepoort CDV vaccine strain (OP-CDV) induces extensive syncytia formation. Here, we investigated the roles of wild-type fusion (F{sub WT}) and attachment (H{sub WT}) proteins in Vero cells expressing, or not, the canine SLAM receptor by transfection experiments and by studying recombinants viruses expressing different combinations of wild-type and OP-CDV glycoproteins. We show that low fusogenicity is not due to a defect of the envelope proteins to reach the cell surface and that H{sub WT} determines persistent infection in a receptor-dependent manner, emphasizing the role of SLAM as a potent enhancer of fusogenicity. However, importantly, F{sub WT} reduced cell-to-cell fusion independently of the cell surface receptor, thus demonstrating that the fusion protein of the neurovirulent A75/17-CDV strain plays a key role in determining persistent infection.

  18. Simultaneous canine distemper virus, canine adenovirus type 2, and Mycoplasma cynos infection in a dog with pneumonia.

    PubMed

    Chvala, S; Benetka, V; Möstl, K; Zeugswetter, F; Spergser, J; Weissenböck, H

    2007-07-01

    The present case is the first description of a triple infection with canine distemper virus (CDV), canine adenovirus (CAV) type 2, and Mycoplasma cynos in a dog. The 5-month-old female Miniature Pinscher was euthanized because of dyspnea, croaking lung sounds, weight loss, and lymphopenia. Pathologic examination revealed a fibrinous necrotizing pneumonia with large amphophilic intranuclear and acidophilic intracytoplasmatic inclusion bodies in different lung cells. Immunohistochemically, CDV antigen was present in lung and many other organs. In situ hybridization for detection of CAV nucleic acid showed positive signals in the lung only. Polymerase chain reaction of lung tissue and consecutive sequencing of the amplification product identified CAV type 2. Bacteriologic examination of lung tissue yielded large amounts of M cynos. This infection was confirmed by immunohistochemistry detecting abundant positive signals in the lung tissue.

  19. Serologic survey for canine distemper virus and canine parvovirus in free-ranging wild carnivores from Portugal.

    PubMed

    Santos, Nuno; Almendra, Cláudia; Tavares, Luís

    2009-01-01

    A serologic survey for Canine distemper virus (CDV) and canine parvovirus (CPV) was performed on serum and lung extract from an opportunistic sample of 120 free-ranging wild carnivores (13 species) from Portugal, collected from 1995 to 2006. Antibodies to CDV were detected in wolf (Canis lupus; 3/27) and red fox (Vulpes vulpes; 2/22). Antibodies to CPV were detected in wolf (9/28), red fox (2/14), wildcat (Felis silvestris;1/8), genet (Genetta genetta; 17/18), and stone marten (Martes foina; 3/17). Antibodies to CPV were detected throughout the study, whereas for CDV antibodies were detected in 3 of 10 yr and only during winter. The extremely high CPV antibody prevalence in genets is unprecedented. Although based on a limited sample, these data suggest widespread exposure of free-ranging Iberian carnivores to CDV and CPV.

  20. Canine distemper, a re-emerging morbillivirus with complex neuropathogenic mechanisms.

    PubMed

    Griot, Christian; Vandevelde, Marc; Schobesberger, Martina; Zurbriggen, Andreas

    2003-06-01

    Paramyxoviruses are responsible for a wide variety of diseases both in humans and in animals. Common to many paramyxoviruses is the fact that they can cause neurological symptoms in their final host. Newly discovered paramyxoviruses, such as the Hendra and Nipah viruses, show the same pattern of pathogenesis as that of the paramyxoviruses already known. Canine distemper virus (CDV) is a well-studied member of the genus Morbillivirus. Study of the neuropathogenesis of CDV might give insight into disease mechanisms and suggest approaches for the prevention of other recently discovered paramyxovirus infections.

  1. Characterization of monoclonal antibodies directed against the canine distemper virus nucleocapsid protein.

    PubMed

    Masuda, Munemitsu; Sato, Hiroki; Kamata, Hiroshi; Katsuo, Tomoe; Takenaka, Akiko; Miura, Ryuichi; Yoneda, Misako; Tsukiyama-Kohara, Kyoko; Mizumoto, Kiyohisa; Kai, Chieko

    2006-01-01

    We have established four monoclonal antibodies (MAbs) against the nucleocapsid protein (NP) of canine distemper virus (CDV). A competitive binding assay has revealed that the MAbs are directed against two antigenic domains. An immunofluorescence assay using a series of deletion clones of the NP and an immunoprecipitation assay using the NP have revealed that two of the MAbs recognize the C-terminal region of the NP while the other two recognize the tertiary structure of the N-terminal domain. These MAbs reacted with all eight strains of CDV used in this study, but showed different reactivities against measles virus and rinderpest virus.

  2. Atypical necrotizing encephalitis associated with systemic canine distemper virus infection in pups.

    PubMed

    Amude, Alexandre Mendes; Headley, Selwyn Arlington; Alfieri, Amauri Alcindo; Beloni, Suely Nunes Esteves; Alfieri, Alice Fernandes

    2011-12-01

    This report describes the naturally occurring atypical neuropathological manifestation of systemic canine distemper virus (CDV) infection in two 16-day-old Pit Bull pups. CDV-induced changes affected the gray and white matter of the forebrain while sparing the hindbrain. Histologically, there was necrosis with destruction of the nervous parenchyma due to an influx of inflammatory and reactive cells associated with eosinophilic intranuclear inclusion bodies within glial cells. Positive immunoreactivity against CDV antigens was predominantly observed within astrocytes and neurons. RT-PCR was used to amplify CDV-specific amplicons from brain fragments. These findings suggest the participation of CDV in the etiopathogenesis of these lesions.

  3. Canine distemper infection in crab-eating fox (Cerdocyon thous) from Argentina.

    PubMed

    Ferreyra, Hebe; Calderón, Marina G; Marticorena, Damián; Marull, Carolina; Leonardo, Barrios Caro

    2009-10-01

    Canine distemper virus (CDV) has been reported worldwide in wild carnivores and has been cited as the cause of population declines in some species. Crab-eating foxes (Cerdocyon thous) from El Palmar National Park, Argentina, were observed either dead or exhibiting clinical neurologic signs. Samples were taken from two individuals that were laterfound tobe positive for CDV by direct immunofluorescence in brain tissue. Based on molecular studies, the CDV strain had a high percentage of identity compared to CDV strains affecting dogsin Argentina. This is the first report of CDV infection in wild carnivores in Argentina.

  4. Accuracy of a point-of-care ELISA test kit for predicting the presence of protective canine parvovirus and canine distemper virus antibody concentrations in dogs.

    PubMed

    Litster, A L; Pressler, B; Volpe, A; Dubovi, E

    2012-08-01

    Canine parvovirus (CPV) and canine distemper virus (CDV) are highly infectious and often fatal diseases with worldwide distributions, and are important population management considerations in animal shelters. A point-of-care ELISA test kit is available to detect serum antibodies to CPV and CDV, and presumptively to predict protective status. The aim of this study was to determine the diagnostic accuracy of the test compared to CPV hemagglutination inhibition titers and CDV serum neutralization titers determined by a reference laboratory, using sera collected from dogs housed at animal shelters. The ELISA test was used under both field and laboratory conditions and duplicate specimens were processed using an extra wash step. The test kit yielded accurate results (CPV: sensitivity 92.3%, specificity 93.5%; CDV: sensitivity 75.7%, specificity 91.8%) under field conditions. CDV sensitivity was improved by performing the test under laboratory conditions and using an optical density (OD) meter (laboratory performed 94.0%; OD 88.1%). Point-of-care ELISA testing for serum CPV and CDV antibody titers was demonstrated to be a useful tool for determining antibody status when making decisions regarding the need for CPV and/or CDV vaccination and also in animal shelters for population management.

  5. Antigenic characterization of phocine distemper virus causing mass mortality in 2002 and its relationship to other morbilliviruses.

    PubMed

    Wohlsein, P; Müller, G; Haas, L; Siebert, U; Harder, T C; Baumgärtner, W

    2007-01-01

    The antigenic relationship between the phocine distemper virus (PDV) strain causing the epidemic in 2002 and the PDV strain of 1988, canine distemper virus from two dogs and one marten, and one measles virus strain was investigated in vivo and in vitro using monospecific polyclonal and monoclonal antibodies directed against five different proteins of canine or phocine distemper virus (N, P, M, F, H). Epitopic mapping revealed no difference between the PDV strains causing the epidemics in 1988 or 2002. However, the use of these antibodies allowed discrimination between different morbilliviruses including a vaccine strain of canine distemper virus. The major differences among the investigated morbilliviruses were found in the H protein.

  6. Vero cells infected with the Lederle strain of canine distemper virus have increased Fas receptor signaling expression at 15 h post-infection.

    PubMed

    Del Puerto, H L; Martins, A S; Braz, G F; Alves, F; Heinemann, M B; Rajão, D S; Araújo, F C; Martins, S F; Nascimento, D R; Leite, R C; Vasconcelos, A C

    2011-10-18

    We evaluated the expression of the Fas receptor gene in Vero cells infected with the Lederle vaccine strain of canine distemper virus using RT-PCR. Vero cells were plated, and after being grown for 24 h in MEM with 5% FBS, 80-90% confluent monolayer cultures were infected with the virus. The cells were harvested at 3, 6, 9, and 15 h post-infection. Uninfected Vero cells were used as a control. Total RNA was isolated from Vero cells using 1 mL Trizol(®) LS, and RT was performed using 2 μg total RNA. Primer pairs for RT-PCR amplification for the canine distemper virus nucleocapsid gene, the S26 reference gene, and the Vero rFas gene were used to analyze expression in Vero cells. RT-PCR results revealed virus activity at 3, 6, 9, and 15 h in the virus-infected Vero cells. The S26 housekeeping gene was amplified in virus infected and control samples. However, expression of the cell death receptor Fas was detected in Vero cells only at 15 h post-infection. We suggest that the Lederle vaccine induces apoptosis by Fas receptor signaling, possibly through caspase-8 signaling rather than through mitochondrial signaling in the infected cells.

  7. Glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes in dogs infected with canine distemper virus.

    PubMed

    Headley, S A; Soares, I C; Graça, D L

    2001-01-01

    An experiment based on astrocyte immunoreactivity to glial fibrillary acidic protein (GFAP) was designed to determine whether the astrocyte response in canine distemper encephalitis (CDE) was associated with the age of the animal, type of lesion and the cerebellar region affected. Four histopathological types of CDE lesion were examined, namely acute (11 dogs), acute with necrosis (four dogs), subacute (22 dogs) and chronic (six dogs). The animals were divided into three age groups, namely, 0-2 years (27 dogs), 2.1-4 years (12 dogs), and 4.1-12 years (four dogs). Three different cerebellar regions were evaluated. Cerebellar sections from three healthy dogs were used for control purposes. The highest number of astrocytes occurred in the cerebellar white matter and in dogs with acute distemper encephalopathy. In animals with subacute distemper encephalitis, the numbers of astrocytes appeared to increase with age, but the opposite effect occurred in dogs with acute or chronic encephalitis; age appeared not to influence the astrocyte numbers in dogs suffering from acute encephalitis with necrosis.

  8. Coinfection with Hepatozoon sp. and Canine Distemper Virus in a Yellow-throated Marten ( Martes flavigula koreana) in Korea.

    PubMed

    Park, Surim; Choi, Ul Soo; Kim, Eun Ju; Lee, Jong Hyun; Lee, Hae Beom; Cho, Ho Seong; Kim, Wonil; Lim, Chae Woong; Kim, Bumseok

    2016-04-28

    We describe coinfection with Hepatozoon sp. and canine distemper virus (CDV) in a yellow-throated marten ( Martes flavigula koreana). We found Hepatozoon cysts in muscular tissue and viral inclusion bodies in the brain. Hepatozoon sp., and CDV was confirmed in blood and brain, respectively, by PCR.

  9. Roles of an extracellular matrix (ECM) receptor and ECM processing enzymes in demyelinating canine distemper encephalitis.

    PubMed

    Alldinger, S; Gröters, S; Miao, Q; Fonfara, S; Kremmer, E; Baumgärtner, W

    2006-04-01

    Canine distemper virus (CDV) belongs to the genus Morbillivirus of the Paramyxoviridae family. Due to the central nervous system (CNS) tropism of the virus and associated neuropathological changes, demyelinating canine distemper encephalitis (CDE) represents a relevant model for human demyelinating diseases like multiple sclerosis. The present review decribes the role of CD44 antigen (CD44), the principle cell surface receptor for hyaluronate and extracellular matrix (ECM) processing enzymes (matrix metalloproteinases [MMPs]) and their inhibitors (TIMPs) in the pathogenesis of demyelination. In acute and subacute CDE, a plaque-associated CD44 up-regulation is found that parallels astrocyte activation. Likewise, MMPs and TIMPs are prominently up-regulated in these lesions and are expressed mostly by astrocytes and microglia. In chronic lesions, CD44 expression declines together with the number of glial fibrillary acidic protein (GFAP) positive astrocytes. In addition, in this plaque type, CD44 is expressed on the cell membrane of perivascular mononuclear cells. In this phase, a decrease of MMP and TIMP expressions apart from MMP-11, -12, and -13 is obvious. In summary, CD44 and MMPs might be associated with the onset of demyelination and may interact to initiate ECM disturbances. Ligation of CD44 in the early phase may induce chemokines and cytokines and hence initiate and perpetuate the inflammatory process. In the chronic phase, it is conceivable that a MMP-TIMP imbalance may be the motor for lesion progression with a simultaneous influx of CD44-positive activated immune cells.

  10. Demyelination precedes oligodendrocyte loss in canine distemper virus-induced encephalitis.

    PubMed

    Schobesberger, M; Zurbriggen, A; Doherr, M G; Weissenböck, H; Vandevelde, M; Lassmann, H; Griot, C

    2002-01-01

    Canine distemper virus (CDV), a negative-stranded RNA morbillivirus, causes a persistent infection within the central nervous system resulting in a progressive, multifocal demyelinating disease. Demyelination is thought to be caused by a selective alteration of the myelin-producing oligodendrocytes. Metabolic impairment and morphological changes of the oligodendrocytes after CDV infection have previously been observed in vitro as well as in vivo. Until now it has been suggested that the oligodendrocytes completely disappear from CDV-induced demyelinating lesions. However, ultrastructural analysis in brain tissue sections and immunohistochemical examination of oligodendrocytes in dog brain cell cultures contradicted these observations. In this study oligodendrocytes from different categories of CDV-induced lesions were examined by in situ hybridization for proteolipid protein mRNA and--as a new tool employed on canine brain tissue sections--by immunohistochemistry using a monoclonal antibody against 2',3'-cyclic nucleotide 3'-phosphodiesterase, a myelin-specific enzyme. A down-regulation in the myelin gene transcription was detected already before demyelination occurred. However, a decrease in the number of oligodendrocytes was not observed until demyelination became evident. Although there was further depletion of oligodendrocytes in plaques with progressive demyelination, we demonstrated for the first time that these cells were still present in a significant amount even in chronic, completely demyelinated distemper lesions.

  11. First evidence of canine distemper in Brazilian free-ranging felids.

    PubMed

    Nava, Alessandra Ferreira Dales; Cullen, Laury; Sana, Dênis Aléssio; Nardi, Marcello Schiavo; Filho, José Domingues Ramos; Lima, Thiago Ferraz; Abreu, Kauê Cachuba; Ferreira, Fernando

    2008-12-01

    Serum samples from 19 jaguars (Panthera onca), nine pumas (Puma concolor), and two ocelots (Leopardus pardalis) were collected between January 1999 and March of 2005 and tested for presence of canine distemper virus (CDV). All cats were free-ranging animals living in two protected areas in the Brazilian Atlantic Forest. In addition, 111 domestic dogs from nearby areas were sampled for CDV. Our results show the first evidence of CDV exposure in Brazilian free-ranging felids. From the 30 samples analyzed, six jaguars and one puma were tested seropositive for CDV. All seropositive large felids were from Ivinhema State Park, resulting in 31.5% of the sampled jaguars or 60% of the total jaguar population in Ivinhema State Park, and 11.28% of the sampled pumas. From the total 111 domestic dogs sampled, 45 were tested seropositive for CDV. At Morro do Diabo State Park, 34.6% of the dogs sampled were positive for CDV, and 100% at Ivinhema State Park. Canine distemper virus in wild felids seems to be related with home range use and in close association with domestic dogs living in nearby areas.

  12. Epidemiology of canine distemper virus in wild raccoon dogs (Nyctereutes procyonoides) from South Korea.

    PubMed

    Cha, Se-Yeoun; Kim, Eun-Ju; Kang, Min; Jang, Sang-Ho; Lee, Hae-Beom; Jang, Hyung-Kwan

    2012-09-01

    Raccoon dogs (Nyctereutes procyonoides) are widespread and common in South Korea. In 2011, we obtained serum samples from 102 wild raccoon dogs to survey their exposure to canine distemper virus (CDV). Forty-five of the 102 animals (44.1%) were seropositive. Field cases of canine distemper in wild raccoon dogs from 2010 to 2011 were investigated. Fourteen cases of CDV infection were identified by a commercially available CDV antigen detection kit. These cases were used for virus isolation and molecular analysis. Sequence analysis of hemagglutinin genes indicated that all viruses isolated belonged to the Asia-2 genotype. H protein residues which are related to the receptor and host specificity (residues 530 and 549) were analyzed. A glutamic acid (E) residue is present at 530 in all isolates. At 549, a histidine (H) residue was found in five isolates and tyrosine (Y) residue was found in 6 isolates. Our study demonstrated that CDV infection was widespread in wild raccoon dogs in South Korea.

  13. Accumulation of Extracellular Matrix in Advanced Lesions of Canine Distemper Demyelinating Encephalitis.

    PubMed

    Seehusen, Frauke; Al-Azreg, Seham A; Raddatz, Barbara B; Haist, Verena; Puff, Christina; Spitzbarth, Ingo; Ulrich, Reiner; Baumgärtner, Wolfgang

    2016-01-01

    In demyelinating diseases, changes in the quality and quantity of the extracellular matrix (ECM) may contribute to demyelination and failure of myelin repair and axonal sprouting, especially in chronic lesions. To characterize changes in the ECM in canine distemper demyelinating leukoencephalitis (DL), histochemical and immunohistochemical investigations of formalin-fixed paraffin-embedded cerebella using azan, picrosirius red and Gomori`s silver stain as well as antibodies directed against aggrecan, type I and IV collagen, fibronectin, laminin and phosphacan showed alterations of the ECM in CDV-infected dogs. A significantly increased amount of aggrecan was detected in early and late white matter lesions. In addition, the positive signal for collagens I and IV as well as fibronectin was significantly increased in late lesions. Conversely, the expression of phosphacan was significantly decreased in early and more pronounced in late lesions compared to controls. Furthermore, a set of genes involved in ECM was extracted from a publically available microarray data set and was analyzed for differential gene expression. Gene expression of ECM molecules, their biosynthesis pathways, and pro-fibrotic factors was mildly up-regulated whereas expression of matrix remodeling enzymes was up-regulated to a relatively higher extent. Summarized, the observed findings indicate that changes in the quality and content of ECM molecules represent important, mainly post-transcriptional features in advanced canine distemper lesions. Considering the insufficiency of morphological regeneration in chronic distemper lesions, the accumulated ECM seems to play a crucial role upon regenerative processes and may explain the relatively small regenerative potential in late stages of this disease.

  14. Accumulation of Extracellular Matrix in Advanced Lesions of Canine Distemper Demyelinating Encephalitis

    PubMed Central

    Seehusen, Frauke; Al-Azreg, Seham A.; Raddatz, Barbara B.; Haist, Verena; Puff, Christina; Spitzbarth, Ingo; Ulrich, Reiner; Baumgärtner, Wolfgang

    2016-01-01

    In demyelinating diseases, changes in the quality and quantity of the extracellular matrix (ECM) may contribute to demyelination and failure of myelin repair and axonal sprouting, especially in chronic lesions. To characterize changes in the ECM in canine distemper demyelinating leukoencephalitis (DL), histochemical and immunohistochemical investigations of formalin-fixed paraffin-embedded cerebella using azan, picrosirius red and Gomori`s silver stain as well as antibodies directed against aggrecan, type I and IV collagen, fibronectin, laminin and phosphacan showed alterations of the ECM in CDV-infected dogs. A significantly increased amount of aggrecan was detected in early and late white matter lesions. In addition, the positive signal for collagens I and IV as well as fibronectin was significantly increased in late lesions. Conversely, the expression of phosphacan was significantly decreased in early and more pronounced in late lesions compared to controls. Furthermore, a set of genes involved in ECM was extracted from a publically available microarray data set and was analyzed for differential gene expression. Gene expression of ECM molecules, their biosynthesis pathways, and pro-fibrotic factors was mildly up-regulated whereas expression of matrix remodeling enzymes was up-regulated to a relatively higher extent. Summarized, the observed findings indicate that changes in the quality and content of ECM molecules represent important, mainly post-transcriptional features in advanced canine distemper lesions. Considering the insufficiency of morphological regeneration in chronic distemper lesions, the accumulated ECM seems to play a crucial role upon regenerative processes and may explain the relatively small regenerative potential in late stages of this disease. PMID:27441688

  15. A chimeric measles virus with canine distemper envelope protects ferrets from lethal distemper challenge.

    PubMed

    Rouxel, Ronan Nicolas; Svitek, Nicholas; von Messling, Veronika

    2009-08-06

    CDV infects a broad range of carnivores, and over the past decades it has caused outbreaks in a variety of wild carnivore populations. Since the currently available live-attenuated vaccine is not sufficiently safe in these highly susceptible species, we produced a chimeric virus combining the replication complex of the measles Moraten vaccine strain with the envelope of a recent CDV wild type isolate. The resulting virus did not cause disease or immunosuppression in ferrets and conferred protection from challenge with a lethal wild type strain, demonstrating its potential value for wildlife conservation efforts.

  16. Evidence of canine distemper and suggestion of preceding parvovirus-myocarditis in a Eurasian badger (Meles meles).

    PubMed

    Burtscher, Hugo; Url, Angelika

    2007-03-01

    An approximately 1.5-yr-old free-ranging male Eurasian badger (Meles meles) from the eastern part of Austria had macroscopic and microscopic lesions consistent with canine distemper virus infection, including nonsuppurative meningoencephalitis, interstitial pneumonia with accumulation of macrophages in alveoli that contained intranuclear inclusion bodies, vesicular exanthema of the ventral abdomen, and atrophy of lymphoid tissues. Canine distemper virus-antigen was demonstrable in a variety of organs by using immunohistology. In addition, there were widespread areas of fibrosis in the myocardium that were rich in collagen and paucicellular. Because such changes are comparable with sequelae of the acute cardiac form of canine parvovirus (CPV) infection in dogs, it was speculated that this badger may have experienced CPV myocarditis as a cub but that the corresponding antigen or DNA was not detectable due to resolution of the disease.

  17. Pathologic and Molecular Virologic Characterization of a Canine Distemper Outbreak in Farmed Civets.

    PubMed

    Techangamsuwan, S; Banlunara, W; Radtanakatikanon, A; Sommanustweechai, A; Siriaroonrat, B; Lombardini, E D; Rungsipipat, A

    2015-07-01

    In October 2011, a fatal disease outbreak occurred in 3 civet species farmed for their use in the coffee industry in Thailand. The disease quickly killed 20 animals in a mixed population of Asian palm civets (Paradoxurus hermaphroditus; n = 18), a masked palm civet (Paguma larvata; n = 1), and small Indian civet (Viverricula indica; n = 1). Clinical signs consisted of severe lethargy, weakness, vomiting, and diarrhea with associated dehydration, dyspnea, nasal and footpad hyperkeratosis, and seizures. All civets were positive for canine morbillivirus using the commercial canine distemper virus (CDV) antigen test kit. Consistently observed necropsy findings consisted of severe pneumonia and hemorrhagic enteritis. Microscopic examination revealed severe gastroenteritis, bronchointerstitial pneumonia, lymphadenitis, necrotizing dermatitis, nonsuppurative polioencephalitis, and characteristic intranuclear/intracytoplasmic eosinophilic viral inclusions in multiple tissues. Immunohistochemical analysis revealed immunoreactivity of varying intensity, while virus isolation demonstrated typical cytopathic effects. To confirm CDV infection, reverse transcription-polymerase chain reaction against fusion (F), phosphoprotein (P), and hemagglutinin (H) genes showed bands of expected size using conjunctival swabs (9 civets, 1 dog [Canis lupus familiaris] living on the farm). Phylogenetic analyses and restriction fragment length polymorphism results indicated that the civets were infected by the Asia-1 strain of CDV commonly found in dogs in Thailand. The deduced amino acid sequences of the signaling lymphocyte activation molecule binding region of the CDV-H proteins revealed a Y549H mutation in both CDV-infected Asian palm civets (n = 4) and a co-located dog. We report a canine distemper outbreak in a civet colony with lineage classification and a Y549H mutation in noncanid species in Thailand.

  18. Canine distemper virus neutralization activity is low in human serum and it is sensitive to an amino acid substitution in the hemagglutinin protein

    SciTech Connect

    Zhang, Xinsheng; Wallace, Olivia L.; Domi, Arban; Wright, Kevin J.; Driscoll, Jonathan; Anzala, Omu; Sanders, Eduard J.; Kamali, Anatoli; Allen, Susan; Fast, Pat; Gilmour, Jill; Price, Matt A.; Parks, Christopher L.

    2015-08-15

    Serum was analyzed from 146 healthy adult volunteers in eastern Africa to evaluate measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb) prevalence and potency. MV plaque reduction neutralization test (PRNT) results indicated that all sera were positive for MV nAbs. Furthermore, the 50% neutralizing dose (ND50) for the majority of sera corresponded to antibody titers induced by MV vaccination. CDV nAbs titers were low and generally were detected in sera with high MV nAb titers. A mutant CDV was generated that was less sensitive to neutralization by human serum. The mutant virus genome had 10 nucleotide substitutions, which coded for single amino acid substitutions in the fusion (F) and hemagglutinin (H) glycoproteins and two substitutions in the large polymerase (L) protein. The H substitution occurred in a conserved region involved in receptor interactions among morbilliviruses, implying that this region is a target for cross-reactive neutralizing antibodies. - Highlights: • Screened 146 serum samples for measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb). • MV nAb is prevalent in the sera. • CDV neutralizing activity is generally low or absent and when detected it is present in sera with high MV nAb titers. • A neutralization-resistant CDV mutant was isolated using human serum selection. • A mutation was identified in the receptor-binding region of CDV hemagglutinin protein that confers the neutralization resistance.

  19. Evaluation of the antiviral activity of chlorine dioxide and sodium hypochlorite against feline calicivirus, human influenza virus, measles virus, canine distemper virus, human herpesvirus, human adenovirus, canine adenovirus and canine parvovirus.

    PubMed

    Sanekata, Takeshi; Fukuda, Toshiaki; Miura, Takanori; Morino, Hirofumi; Lee, Cheolsung; Maeda, Ken; Araki, Kazuko; Otake, Toru; Kawahata, Takuya; Shibata, Takashi

    2010-06-01

    We evaluated the antiviral activity of a chlorine dioxide gas solution (CD) and sodium hypochlorite (SH) against feline calicivirus, human influenza virus, measles virus, canine distemper virus, human herpesvirus, human adenovirus, canine adenovirus and canine parvovirus. CD at concentrations ranging from 1 to 100 ppm produced potent antiviral activity, inactivating >or= 99.9% of the viruses with a 15 sec treatment for sensitization. The antiviral activity of CD was approximately 10 times higher than that of SH.

  20. An outbreak of canine distemper virus in tigers (Panthera tigris): possible transmission from wild animals to zoo animals.

    PubMed

    Nagao, Yumiko; Nishio, Yohei; Shiomoda, Hiroshi; Tamaru, Seiji; Shimojima, Masayuki; Goto, Megumi; Une, Yumi; Sato, Azusa; Ikebe, Yusuke; Maeda, Ken

    2012-06-01

    Canine distemper virus (CDV), a morbillivirus that causes one of the most contagious and lethal viral diseases known in canids, has an expanding host range, including wild animals. Since December 2009, several dead or dying wild raccoon dogs (Nyctereutes procyonoides) were found in and around one safari-style zoo in Japan, and CDV was isolated from four of these animals. In the subsequent months (January to February 2010), 12 tigers (Panthera tigris) in the zoo developed respiratory and gastrointestinal diseases, and CDV RNA was detected in fecal samples of the examined tigers. In March 2010, one of the tigers developed a neurological disorder and died; CDV was isolated from the lung of this animal. Sequence analysis of the complete hemagglutinin (H) gene and the signal peptide region of the fusion (F) gene showed high homology among these isolates (99.8-100%), indicating that CDV might have been transmitted from raccoon dog to tiger. In addition, these isolates belonged to genotype Asia-1 and had lower homology (<90%) to the vaccine strain (Onderstepoort). Seropositivity of lions (Panthera leo) in the zoo and wild bears (Ursus thibetanus) captured around this area supported the theory that a CDV epidemic had occurred in many mammal species in and around the zoo. These results indicate a risk of CDV transmission among many animal species, including large felids and endangered species.

  1. Use of hydrophilic extra-viral domain of canine distemper virus H protein for enzyme-linked immunosorbent assay development.

    PubMed

    Cho, Ki-hyun; Kim, Jeongmi; Yoo, Hyun-ah; Kim, Dae-hee; Park, Seung-yong; Song, Chang-seon; Choi, In-soo; Lee, Joong-bok

    2014-12-01

    Simple methods for measuring the levels of serum antibody against canine distemper virus (CDV) would assist in the effective vaccination of dogs. To develop an enzyme-linked immunosorbent assay (ELISA) specific for CDV, we expressed hydrophilic extra-viral domain (HEVD) protein of the A75/17-CDV H gene in a pET 28a plasmid-based Escherichia (E.) coli vector system. Expression was confirmed by dot and Western blotting. We proposed that detection of E. coli-expressed H protein might be conformation- dependent because intensities of the reactions observed with these two methods varied. The H gene HEVD protein was further purified and used as an antigen for an ELISA. Samples from dogs with undetectable to high anti-CDV antibody titers were analyzed using this HEVD-specific ELISA and a commercial CDV antibody detection kit (ImmunoComb). Levels of HEVD antigenicity measured with the assays and immunochromatography correlated. These data indicated that the HEDV protein may be used as antigen to develop techniques for detecting antibodies against CDV.

  2. Disease manifestations of canine distemper virus infection in ferrets are modulated by vitamin A status.

    PubMed

    Rodeheffer, Carey; von Messling, Veronika; Milot, Sylvain; Lepine, François; Manges, Amee R; Ward, Brian J

    2007-08-01

    The measles virus (MV) causes half a million childhood deaths annually. Vitamin A supplements significantly reduce measles-associated mortality and morbidity. The mechanisms whereby vitamin A acts against MV are not understood and currently there is no satisfactory small animal model for MV infection. We report on the development of a ferret model to study antiviral activity of vitamin A against canine distemper virus (CDV). CDV is closely related to MV at the molecular level and distemper in ferrets mimics measles in humans. We infected vitamin A-replete (control) and vitamin A-depleted ferrets with CDV and assessed the ability of high-dose vitamin A supplements to influence CDV disease. In control ferrets, CDV infection caused fever, rash, conjunctivitis, cough, coryza, and diarrhea. In contrast, control ferrets that were given 30 mg of vitamin A did not develop typical distemper after infection and exhibited only a mild rash. The supplement did not negatively affect ferret health and resulted in a 100% increase in serum and liver vitamin A concentrations. We also found that profound vitamin A deficiency is inducible in ferrets and can be rapidly reversed upon high-dose vitamin A supplementation. Vitamin A deficiency caused anorexia, diarrhea, cataracts, behavioral abnormalities, and ultimately death, with or without CDV infection. All ferrets that received vitamin A supplements, however, recovered uneventfully from CDV infection. These results replicate many aspects of the observations of vitamin A therapy in humans with measles and suggest that CDV infection in ferrets is an appropriate model for the study of the antiviral mechanism of vitamin A.

  3. The V protein of canine distemper virus is required for virus replication in human epithelial cells.

    PubMed

    Otsuki, Noriyuki; Nakatsu, Yuichiro; Kubota, Toru; Sekizuka, Tsuyoshi; Seki, Fumio; Sakai, Kouji; Kuroda, Makoto; Yamaguchi, Ryoji; Takeda, Makoto

    2013-01-01

    Canine distemper virus (CDV) becomes able to use human receptors through a single amino acid substitution in the H protein. In addition, CDV strains possessing an intact C protein replicate well in human epithelial H358 cells. The present study showed that CDV strain 007Lm, which was isolated from lymph node tissue of a dog with distemper, failed to replicate in H358 cells, although it possessed an intact C protein. Sequence analyses suggested that a cysteine-to-tyrosine substitution at position 267 of the V protein caused this growth defect. Analyses using H358 cells constitutively expressing the CDV V protein showed that the V protein with a cysteine, but not that with a tyrosine, at this position effectively blocked the interferon-stimulated signal transduction pathway, and supported virus replication of 007Lm in H358 cells. Thus, the V protein as well as the C protein appears to be functional and essential for CDV replication in human epithelial cells.

  4. Epitope mapping of Canine distemper virus phosphoprotein by monoclonal antibodies.

    PubMed

    Sugai, Akihiro; Kooriyama, Takanori; Sato, Hiroki; Yoneda, Misako; Kai, Chieko

    2009-12-01

    The gene for phosphoprotein (P) of CDV encodes three different proteins, P, V, and C. The P protein is involved in viral gene transcription and replication. In the present study, we produced MAbs against a unique domain of the CDV-P protein, from aa 232 to 507, and determined their antigenic sites. By immunizing BALB/c mice with the recombinant P protein-specific fragment, we obtained six MAbs. Competitive binding inhibition assays revealed that they recognized two distinct regions of the P protein. Western blot analysis and immunofluorescence assays using deletion mutants of the unique C-terminus of the CDV-P protein revealed that all MAbs recognized a central short region (aa 233-303) of the CDV-P protein. In addition, linear and conformational epitopes have been determined, and at least four antigenic sites exist in the P protein central region. Furthermore, four of the MAbs were found to react with the P protein of recent Japanese field isolates but not with that of the older CDV strains, including a vaccine strain. Thus, these MAbs could be clinically useful for quick diagnosis during the CDV outbreaks.

  5. Experimental Adaptation of Wild-Type Canine Distemper Virus (CDV) to the Human Entry Receptor CD150

    PubMed Central

    Bieringer, Maria; Han, Jung Woo; Kendl, Sabine; Khosravi, Mojtaba; Plattet, Philippe; Schneider-Schaulies, Jürgen

    2013-01-01

    Canine distemper virus (CDV), a close relative of measles virus (MV), is widespread and well known for its broad host range. When the goal of measles eradication may be achieved, and when measles vaccination will be stopped, CDV might eventually cross the species barrier to humans and emerge as a new human pathogen. In order to get an impression how fast such alterations may occur, we characterized required adaptive mutations to the human entry receptors CD150 (SLAM) and nectin-4 as first step to infect human target cells. Recombinant wild-type CDV-A75/17red adapted quickly to growth in human H358 epithelial cells expressing human nectin-4. Sequencing of the viral attachment proteins (hemagglutinin, H, and fusion protein, F) genes revealed that no adaptive alteration was required to utilize human nectin-4. In contrast, the virus replicated only to low titres (102 pfu/ml) in Vero cells expressing human CD150 (Vero-hSLAM). After three passages using these cells virus was adapted to human CD150 and replicated to high titres (105 pfu/ml). Sequence analyses revealed that only one amino acid exchange in the H-protein at position 540 Asp→Gly (D540G) was required for functional adaptation to human CD150. Structural modelling suggests that the adaptive mutation D540G in H reflects the sequence alteration from canine to human CD150 at position 70 and 71 from Pro to Leu (P70L) and Gly to Glu (G71E), and compensates for the gain of a negative charge in the human CD150 molecule. Using this model system our data indicate that only a minimal alteration, in this case one adaptive mutation, is required for adaptation of CDV to the human entry receptors, and help to understand the molecular basis why this adaptive mutation occurs. PMID:23554862

  6. Experimental adaptation of wild-type canine distemper virus (CDV) to the human entry receptor CD150.

    PubMed

    Bieringer, Maria; Han, Jung Woo; Kendl, Sabine; Khosravi, Mojtaba; Plattet, Philippe; Schneider-Schaulies, Jürgen

    2013-01-01

    Canine distemper virus (CDV), a close relative of measles virus (MV), is widespread and well known for its broad host range. When the goal of measles eradication may be achieved, and when measles vaccination will be stopped, CDV might eventually cross the species barrier to humans and emerge as a new human pathogen. In order to get an impression how fast such alterations may occur, we characterized required adaptive mutations to the human entry receptors CD150 (SLAM) and nectin-4 as first step to infect human target cells. Recombinant wild-type CDV-A75/17(red) adapted quickly to growth in human H358 epithelial cells expressing human nectin-4. Sequencing of the viral attachment proteins (hemagglutinin, H, and fusion protein, F) genes revealed that no adaptive alteration was required to utilize human nectin-4. In contrast, the virus replicated only to low titres (10(2) pfu/ml) in Vero cells expressing human CD150 (Vero-hSLAM). After three passages using these cells virus was adapted to human CD150 and replicated to high titres (10(5) pfu/ml). Sequence analyses revealed that only one amino acid exchange in the H-protein at position 540 Asp→Gly (D540G) was required for functional adaptation to human CD150. Structural modelling suggests that the adaptive mutation D540G in H reflects the sequence alteration from canine to human CD150 at position 70 and 71 from Pro to Leu (P70L) and Gly to Glu (G71E), and compensates for the gain of a negative charge in the human CD150 molecule. Using this model system our data indicate that only a minimal alteration, in this case one adaptive mutation, is required for adaptation of CDV to the human entry receptors, and help to understand the molecular basis why this adaptive mutation occurs.

  7. Isolation and phylogenetic analysis of canine distemper virus among domestic dogs in Vietnam.

    PubMed

    Nguyen, Dung Van; Suzuki, Junko; Minami, Shohei; Yonemitsu, Kenzo; Nagata, Nao; Kuwata, Ryusei; Shimoda, Hiroshi; Vu, Chien Kim; Truong, Thuy Quoc; Maeda, Ken

    2017-01-20

    Canine distemper virus (CDV) is one of the most serious pathogens found in many species of carnivores, including domestic dogs. In this study, hemagglutinin (H) genes were detected in five domestic Vietnamese dogs with diarrhea, and two CDVs were successfully isolated from dogs positive for H genes. The complete genome of one isolate, CDV/dog/HCM/33/140816, was determined. Phylogenetic analysis showed that all Vietnamese CDVs belonged to the Asia-1 genotype. In addition, the H proteins of Vietnamese CDV strains were the most homologous to those of Chinese CDVs (98.4% to 99.3% identity). These results indicated that the Asia-1 genotype of CDV was the predominant genotype circulating among the domestic dog population in Vietnam and that transboundary transmission of CDV has occurred between Vietnam and China.

  8. Aromatase expression in the cerebellum of the dog infected with canine distemper virus.

    PubMed

    Yarim, Murat; Gulbahar, Mustafa Yavuz; Guvenc, Tolga; Karahan, Siyami; Harada, Nobuhiro; Kabak, Yonca Betil; Karayigit, Mehmet Onder

    2010-01-01

    Aromatase is the enzyme that catalyzes the biosynthesis of estrogens. It is implicated in neuroprotection.The present study investigated aromatase expression in the cerebellum of dogs infected with canine distemper virus (CDV), a disease characterized by demyelination in the white matter of the cerebellum. The presence of CDV infection was confirmed on the basis of histopathology and immunohistochemical localization of CDV antigen in glial cells of the white matter.The number of aromatase immunoreactive astrocytes were significantly (p < 0.05) higher in CDV-infected dogs compared to control dogs. The results suggest that astrocytes respond to invasion and persistence of CDV by means of increased estrogen production.The results also suggest that the high level of estrogen expression is maintained similarly throughout all stages of the disease since the number of aromatase immunoreactive astrocytes did not vary during the different stages of CDV infection.

  9. Pathological and phylogenetic features of prevalent canine distemper viruses in wild masked palm civets in Japan.

    PubMed

    Takayama, Ikuyo; Kubo, Masahito; Takenaka, Akiko; Fujita, Kentaro; Sugiyama, Takaaki; Arai, Tetsuro; Yoneda, Misako; Sato, Hiroki; Yanai, Tokuma; Kai, Chieko

    2009-11-01

    Ten wild masked palm civets infected with canine distemper virus (CDV), captured in Japan from 2005 to 2007, were histopathologically and phylogenetically analyzed. Phylogenetic analysis based on the amino acid sequences of the H protein of two CDV isolates from masked palm civets revealed that the two isolates were classified into the clade of recent isolates in Japan. Histopathologically marked lesions of virus encephalitis were present in the brain, whereas gastrointestinal lesions were absent or at a mild degree. The distribution of the lesions resembles that of recent CDV cases in dogs. Therefore, recent CDV infections in masked palm civets could be caused by recently prevalent CDV in dogs. The possibility of the masked palm civet as a spreader of CDV among wildlife is also discussed.

  10. Isolation and phylogenetic analysis of canine distemper virus among domestic dogs in Vietnam

    PubMed Central

    NGUYEN, Dung Van; SUZUKI, Junko; MINAMI, Shohei; YONEMITSU, Kenzo; NAGATA, Nao; KUWATA, Ryusei; SHIMODA, Hiroshi; VU, Chien Kim; TRUONG, Thuy Quoc; MAEDA, Ken

    2016-01-01

    Canine distemper virus (CDV) is one of the most serious pathogens found in many species of carnivores, including domestic dogs. In this study, hemagglutinin (H) genes were detected in five domestic Vietnamese dogs with diarrhea, and two CDVs were successfully isolated from dogs positive for H genes. The complete genome of one isolate, CDV/dog/HCM/33/140816, was determined. Phylogenetic analysis showed that all Vietnamese CDVs belonged to the Asia-1 genotype. In addition, the H proteins of Vietnamese CDV strains were the most homologous to those of Chinese CDVs (98.4% to 99.3% identity). These results indicated that the Asia-1 genotype of CDV was the predominant genotype circulating among the domestic dog population in Vietnam and that transboundary transmission of CDV has occurred between Vietnam and China. PMID:27746406

  11. 9 CFR 113.317 - Parvovirus Vaccine (Canine).

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Parvovirus Vaccine (Canine). 113.317... Virus Vaccines § 113.317 Parvovirus Vaccine (Canine). Parvovirus Vaccine recommended for use in dogs... pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All serials...

  12. 9 CFR 113.317 - Parvovirus Vaccine (Canine).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Parvovirus Vaccine (Canine). 113.317... Virus Vaccines § 113.317 Parvovirus Vaccine (Canine). Parvovirus Vaccine recommended for use in dogs... pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All serials...

  13. 9 CFR 113.317 - Parvovirus Vaccine (Canine).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Parvovirus Vaccine (Canine). 113.317... Virus Vaccines § 113.317 Parvovirus Vaccine (Canine). Parvovirus Vaccine recommended for use in dogs... pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All serials...

  14. 9 CFR 113.317 - Parvovirus Vaccine (Canine).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Parvovirus Vaccine (Canine). 113.317... Virus Vaccines § 113.317 Parvovirus Vaccine (Canine). Parvovirus Vaccine recommended for use in dogs... pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All serials...

  15. 9 CFR 113.317 - Parvovirus Vaccine (Canine).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Parvovirus Vaccine (Canine). 113.317... Virus Vaccines § 113.317 Parvovirus Vaccine (Canine). Parvovirus Vaccine recommended for use in dogs... pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All serials...

  16. Canine distemper virus infects canine keratinocytes and immune cells by using overlapping and distinct regions located on one side of the attachment protein.

    PubMed

    Langedijk, Johannes P M; Janda, Jozef; Origgi, Francesco C; Örvell, Claes; Vandevelde, Marc; Zurbriggen, Andreas; Plattet, Philippe

    2011-11-01

    The morbilliviruses measles virus (MeV) and canine distemper virus (CDV) both rely on two surface glycoproteins, the attachment (H) and fusion proteins, to promote fusion activity for viral cell entry. Growing evidence suggests that morbilliviruses infect multiple cell types by binding to distinct host cell surface receptors. Currently, the only known in vivo receptor used by morbilliviruses is CD150/SLAM, a molecule expressed in certain immune cells. Here we investigated the usage of multiple receptors by the highly virulent and demyelinating CDV strain A75/17. We based our study on the assumption that CDV-H may interact with receptors similar to those for MeV, and we conducted systematic alanine-scanning mutagenesis on CDV-H throughout one side of the β-propeller documented in MeV-H to contain multiple receptor-binding sites. Functional and biochemical assays performed with SLAM-expressing cells and primary canine epithelial keratinocytes identified 11 residues mutation of which selectively abrogated fusion in keratinocytes. Among these, four were identical to amino acids identified in MeV-H as residues contacting a putative receptor expressed in polarized epithelial cells. Strikingly, when mapped on a CDV-H structural model, all residues clustered in or around a recessed groove located on one side of CDV-H. In contrast, reported CDV-H mutants with SLAM-dependent fusion deficiencies were characterized by additional impairments to the promotion of fusion in keratinocytes. Furthermore, upon transfer of residues that selectively impaired fusion induction in keratinocytes into the CDV-H of the vaccine strain, fusion remained largely unaltered. Taken together, our results suggest that a restricted region on one side of CDV-H contains distinct and overlapping sites that control functional interaction with multiple receptors.

  17. Canine Distemper Virus Infects Canine Keratinocytes and Immune Cells by Using Overlapping and Distinct Regions Located on One Side of the Attachment Protein▿

    PubMed Central

    Langedijk, Johannes P. M.; Janda, Jozef; Origgi, Francesco C.; Örvell, Claes; Vandevelde, Marc; Zurbriggen, Andreas; Plattet, Philippe

    2011-01-01

    The morbilliviruses measles virus (MeV) and canine distemper virus (CDV) both rely on two surface glycoproteins, the attachment (H) and fusion proteins, to promote fusion activity for viral cell entry. Growing evidence suggests that morbilliviruses infect multiple cell types by binding to distinct host cell surface receptors. Currently, the only known in vivo receptor used by morbilliviruses is CD150/SLAM, a molecule expressed in certain immune cells. Here we investigated the usage of multiple receptors by the highly virulent and demyelinating CDV strain A75/17. We based our study on the assumption that CDV-H may interact with receptors similar to those for MeV, and we conducted systematic alanine-scanning mutagenesis on CDV-H throughout one side of the β-propeller documented in MeV-H to contain multiple receptor-binding sites. Functional and biochemical assays performed with SLAM-expressing cells and primary canine epithelial keratinocytes identified 11 residues mutation of which selectively abrogated fusion in keratinocytes. Among these, four were identical to amino acids identified in MeV-H as residues contacting a putative receptor expressed in polarized epithelial cells. Strikingly, when mapped on a CDV-H structural model, all residues clustered in or around a recessed groove located on one side of CDV-H. In contrast, reported CDV-H mutants with SLAM-dependent fusion deficiencies were characterized by additional impairments to the promotion of fusion in keratinocytes. Furthermore, upon transfer of residues that selectively impaired fusion induction in keratinocytes into the CDV-H of the vaccine strain, fusion remained largely unaltered. Taken together, our results suggest that a restricted region on one side of CDV-H contains distinct and overlapping sites that control functional interaction with multiple receptors. PMID:21849439

  18. Deduced sequences of the membrane fusion and attachment proteins of canine distemper viruses isolated from dogs and wild animals in Korea.

    PubMed

    Bae, Chae-Wun; Lee, Joong-Bok; Park, Seung-Yong; Song, Chang-Seon; Lee, Nak-Hyung; Seo, Kun-Ho; Kang, Young-Sun; Park, Choi-Kyu; Choi, In-Soo

    2013-08-01

    Canine distemper virus (CDV) causes highly contagious respiratory, gastrointestinal, and neurological diseases in wild and domestic animal species. Despite a broad vaccination campaign, the disease is still a serious problem worldwide. In this study, six field CDV strains were isolated from three dogs, two raccoon dogs, and one badger in Korea. The full sequence of the genes encoding fusion (F) and hemagglutinin (H) proteins were compared with those of other CDVs including field and vaccine strains. The phylogenetic analysis for the F and H genes indicated that the two CDV strains isolated from dogs were most closely related to Chinese strains in the Asia-1 genotype. Another four strains were closely related to Japanese strains in the Asia-2 genotype. The six currently isolated strains shared 90.2-92.1% and 88.2-91.8% identities with eight commercial vaccine strains in their nucleotide and amino acid sequences of the F protein, respectively. They also showed 90.1-91.4% and 87.8-90.7% identities with the same vaccine strains in their nucleotide and deduced amino acid sequences of the H protein, respectively. Different N-linked glycosylation sites were identified in the F and H genes of the six isolates from the prototype vaccine strain Onderstepoort. Collectively, these results demonstrate that at least two different CDV genotypes currently exist in Korea. The considerable genetic differences between the vaccine strains and wild-type isolates would be a major factor of the incomplete protection of dogs from CDV infections.

  19. SLAM- and Nectin-4-Independent Noncytolytic Spread of Canine Distemper Virus in Astrocytes

    PubMed Central

    Alves, Lisa; Khosravi, Mojtaba; Avila, Mislay; Ader-Ebert, Nadine; Bringolf, Fanny; Zurbriggen, Andreas; Vandevelde, Marc

    2015-01-01

    ABSTRACT Measles and canine distemper viruses (MeV and CDV, respectively) first replicate in lymphatic and epithelial tissues by using SLAM and nectin-4 as entry receptors, respectively. The viruses may also invade the brain to establish persistent infections, triggering fatal complications, such as subacute sclerosis pan-encephalitis (SSPE) in MeV infection or chronic, multiple sclerosis-like, multifocal demyelinating lesions in the case of CDV infection. In both diseases, persistence is mediated by viral nucleocapsids that do not require packaging into particles for infectivity but are directly transmitted from cell to cell (neurons in SSPE or astrocytes in distemper encephalitis), presumably by relying on restricted microfusion events. Indeed, although morphological evidence of fusion remained undetectable, viral fusion machineries and, thus, a putative cellular receptor, were shown to contribute to persistent infections. Here, we first showed that nectin-4-dependent cell-cell fusion in Vero cells, triggered by a demyelinating CDV strain, remained extremely limited, thereby supporting a potential role of nectin-4 in mediating persistent infections in astrocytes. However, nectin-4 could not be detected in either primary cultured astrocytes or the white matter of tissue sections. In addition, a bioengineered “nectin-4-blind” recombinant CDV retained full cell-to-cell transmission efficacy in primary astrocytes. Combined with our previous report demonstrating the absence of SLAM expression in astrocytes, these findings are suggestive for the existence of a hitherto unrecognized third CDV receptor expressed by glial cells that contributes to the induction of noncytolytic cell-to-cell viral transmission in astrocytes. IMPORTANCE While persistent measles virus (MeV) infection induces SSPE in humans, persistent canine distemper virus (CDV) infection causes chronic progressive or relapsing demyelination in carnivores. Common to both central nervous system (CNS

  20. Comparison of tissue and fluid samples for the early detection of canine distemper virus in experimentally infected dogs.

    PubMed

    Kim, Doo; Jeoung, Seok-Yong; Ahn, So-Jeo; Lee, Jong-Hyun; Pak, Son-Il; Kwon, Hyuk-Moo

    2006-08-01

    The clinical utility of various specimens was examined for the early diagnosis of canine distemper (CD). Seven healthy dogs at 17 weeks of age were experimentally infected with a field isolate of canine distemper virus. The RT-PCR was carried out to detect CDV NP gene. Dogs showed mild fever and leukopenia, however, typical clinical signs of CD were not seen through the experimental period. CDV amplicons were detected more, earlier and for longer period in the conjunctival swabs than in the other samples employed. These results suggested that conjunctival swab samples, which are easy to obtain and non-invasive, would be the most suitable and practical specimen for the early antemortem diagnosis of CDV infection.

  1. Rabies and canine distemper virus epidemics in the red fox population of northern Italy (2006-2010).

    PubMed

    Nouvellet, Pierre; Donnelly, Christl A; De Nardi, Marco; Rhodes, Chris J; De Benedictis, Paola; Citterio, Carlo; Obber, Federica; Lorenzetto, Monica; Pozza, Manuela Dalla; Cauchemez, Simon; Cattoli, Giovanni

    2013-01-01

    Since 2006 the red fox (Vulpes vulpes) population in north-eastern Italy has experienced an epidemic of canine distemper virus (CDV). Additionally, in 2008, after a thirteen-year absence from Italy, fox rabies was re-introduced in the Udine province at the national border with Slovenia. Disease intervention strategies are being developed and implemented to control rabies in this area and minimise risk to human health. Here we present empirical data and the epidemiological picture relating to these epidemics in the period 2006-2010. Of important significance for epidemiological studies of wild animals, basic mathematical models are developed to exploit information collected from the surveillance program on dead and/or living animals in order to assess the incidence of infection. These models are also used to estimate the rate of transmission of both diseases and the rate of vaccination, while correcting for a bias in early collection of CDV samples. We found that the rate of rabies transmission was roughly twice that of CDV, with an estimated effective contact between infected and susceptible fox leading to a new infection occurring once every 3 days for rabies, and once a week for CDV. We also inferred that during the early stage of the CDV epidemic, a bias in the monitoring protocol resulted in a positive sample being almost 10 times more likely to be collected than a negative sample. We estimated the rate of intake of oral vaccine at 0.006 per day, allowing us to estimate that roughly 68% of the foxes would be immunised. This was confirmed by field observations. Finally we discuss the implications for the eco-epidemiological dynamics of both epidemics in relation to control measures.

  2. Dynamics of a morbillivirus at the domestic-wildlife interface: Canine distemper virus in domestic dogs and lions.

    PubMed

    Viana, Mafalda; Cleaveland, Sarah; Matthiopoulos, Jason; Halliday, Jo; Packer, Craig; Craft, Meggan E; Hampson, Katie; Czupryna, Anna; Dobson, Andrew P; Dubovi, Edward J; Ernest, Eblate; Fyumagwa, Robert; Hoare, Richard; Hopcraft, J Grant C; Horton, Daniel L; Kaare, Magai T; Kanellos, Theo; Lankester, Felix; Mentzel, Christine; Mlengeya, Titus; Mzimbiri, Imam; Takahashi, Emi; Willett, Brian; Haydon, Daniel T; Lembo, Tiziana

    2015-02-03

    Morbilliviruses cause many diseases of medical and veterinary importance, and although some (e.g., measles and rinderpest) have been controlled successfully, others, such as canine distemper virus (CDV), are a growing concern. A propensity for host-switching has resulted in CDV emergence in new species, including endangered wildlife, posing challenges for controlling disease in multispecies communities. CDV is typically associated with domestic dogs, but little is known about its maintenance and transmission in species-rich areas or about the potential role of domestic dog vaccination as a means of reducing disease threats to wildlife. We address these questions by analyzing a long-term serological dataset of CDV in lions and domestic dogs from Tanzania's Serengeti ecosystem. Using a Bayesian state-space model, we show that dynamics of CDV have changed considerably over the past three decades. Initially, peaks of CDV infection in dogs preceded those in lions, suggesting that spill-over from dogs was the main driver of infection in wildlife. However, despite dog-to-lion transmission dominating cross-species transmission models, infection peaks in lions became more frequent and asynchronous from those in dogs, suggesting that other wildlife species may play a role in a potentially complex maintenance community. Widespread mass vaccination of domestic dogs reduced the probability of infection in dogs and the size of outbreaks but did not prevent transmission to or peaks of infection in lions. This study demonstrates the complexity of CDV dynamics in natural ecosystems and the value of long-term, large-scale datasets for investigating transmission patterns and evaluating disease control strategies.

  3. Dynamics of a morbillivirus at the domestic–wildlife interface: Canine distemper virus in domestic dogs and lions

    PubMed Central

    Viana, Mafalda; Matthiopoulos, Jason; Halliday, Jo; Packer, Craig; Craft, Meggan E.; Hampson, Katie; Czupryna, Anna; Dobson, Andrew P.; Dubovi, Edward J.; Ernest, Eblate; Fyumagwa, Robert; Hoare, Richard; Hopcraft, J. Grant C.; Horton, Daniel L.; Kaare, Magai T.; Kanellos, Theo; Lankester, Felix; Mentzel, Christine; Mlengeya, Titus; Mzimbiri, Imam; Takahashi, Emi; Willett, Brian; Haydon, Daniel T.; Lembo, Tiziana

    2015-01-01

    Morbilliviruses cause many diseases of medical and veterinary importance, and although some (e.g., measles and rinderpest) have been controlled successfully, others, such as canine distemper virus (CDV), are a growing concern. A propensity for host-switching has resulted in CDV emergence in new species, including endangered wildlife, posing challenges for controlling disease in multispecies communities. CDV is typically associated with domestic dogs, but little is known about its maintenance and transmission in species-rich areas or about the potential role of domestic dog vaccination as a means of reducing disease threats to wildlife. We address these questions by analyzing a long-term serological dataset of CDV in lions and domestic dogs from Tanzania’s Serengeti ecosystem. Using a Bayesian state–space model, we show that dynamics of CDV have changed considerably over the past three decades. Initially, peaks of CDV infection in dogs preceded those in lions, suggesting that spill-over from dogs was the main driver of infection in wildlife. However, despite dog-to-lion transmission dominating cross-species transmission models, infection peaks in lions became more frequent and asynchronous from those in dogs, suggesting that other wildlife species may play a role in a potentially complex maintenance community. Widespread mass vaccination of domestic dogs reduced the probability of infection in dogs and the size of outbreaks but did not prevent transmission to or peaks of infection in lions. This study demonstrates the complexity of CDV dynamics in natural ecosystems and the value of long-term, large-scale datasets for investigating transmission patterns and evaluating disease control strategies. PMID:25605919

  4. Canine distemper virus neutralization activity is low in human serum and it is sensitive to an amino acid substitution in the hemagglutinin protein.

    PubMed

    Zhang, Xinsheng; Wallace, Olivia L; Domi, Arban; Wright, Kevin J; Driscoll, Jonathan; Anzala, Omu; Sanders, Eduard J; Kamali, Anatoli; Karita, Etienne; Allen, Susan; Fast, Pat; Gilmour, Jill; Price, Matt A; Parks, Christopher L

    2015-08-01

    Serum was analyzed from 146 healthy adult volunteers in eastern Africa to evaluate measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb) prevalence and potency. MV plaque reduction neutralization test (PRNT) results indicated that all sera were positive for MV nAbs. Furthermore, the 50% neutralizing dose (ND50) for the majority of sera corresponded to antibody titers induced by MV vaccination. CDV nAbs titers were low and generally were detected in sera with high MV nAb titers. A mutant CDV was generated that was less sensitive to neutralization by human serum. The mutant virus genome had 10 nucleotide substitutions, which coded for single amino acid substitutions in the fusion (F) and hemagglutinin (H) glycoproteins and two substitutions in the large polymerase (L) protein. The H substitution occurred in a conserved region involved in receptor interactions among morbilliviruses, implying that this region is a target for cross-reactive neutralizing antibodies.

  5. Dynamic changes of Foxp3(+) regulatory T cells in spleen and brain of canine distemper virus-infected dogs.

    PubMed

    Qeska, V; Barthel, Y; Iseringhausen, M; Tipold, A; Stein, V M; Khan, M A; Baumgärtner, W; Beineke, A

    2013-12-15

    Canine distemper virus (CDV) infection causes immunosuppression and demyelinating leukoencephalitis in dogs. In viral diseases, an ambiguous function of regulatory T cells (Treg), with both beneficial effects by reducing immunopathology and detrimental effects by inhibiting antiviral immunity, has been described. However, the role of Treg in the pathogenesis of canine distemper remains unknown. In order to determine the effect of CDV upon immune homeostasis, the amount of Foxp3(+) Treg in spleen and brain of naturally infected dogs has been determined by immunohistochemistry. In addition, splenic cytokine expression has been quantified by reverse transcriptase polymerase chain reaction. Splenic depletion of Foxp3(+) Treg was associated with an increased mRNA-expression of tumor necrosis factor and decreased transcription of interleukin-2 in the acute disease phase, indicative of disturbed immunological counter regulation in peripheral lymphoid organs. In the brain, a lack of Foxp3(+) Treg in predemyelinating and early demyelinating lesions and significantly increased infiltrations of Foxp3(+) Treg in chronic demyelinating lesions were observed. In conclusion, disturbed peripheral and CNS immune regulation associated with a reduction of Treg represents a potential prerequisite for excessive neuroinflammation and early lesion development in canine distemper leukoencephalitis.

  6. Nearby clusters of hemagglutinin residues sustain SLAM-dependent canine distemper virus entry in peripheral blood mononuclear cells.

    PubMed

    von Messling, Veronika; Oezguen, Numan; Zheng, Qi; Vongpunsawad, Sompong; Braun, Werner; Cattaneo, Roberto

    2005-05-01

    Signaling lymphocytic activation molecule (SLAM, CD150) is the universal morbillivirus receptor. Based on the identification of measles virus (MV) hemagglutinin (H) amino acids supporting human SLAM-dependent cell entry, we mutated canine distemper virus (CDV) H and identified residues necessary for efficient canine SLAM-dependent membrane fusion. These residues are located in two nearby clusters in a new CDV H structural model. To completely abolish SLAM-dependent fusion, combinations of mutations were necessary. We rescued a SLAM-blind recombinant CDV with six mutations that did not infect ferret peripheral blood mononuclear cells while retaining full infectivity in epithelial cells.

  7. Canine distemper virus associated with a lethal outbreak in monkeys can readily adapt to use human receptors.

    PubMed

    Sakai, Kouji; Yoshikawa, Tomoki; Seki, Fumio; Fukushi, Shuetsu; Tahara, Maino; Nagata, Noriyo; Ami, Yasushi; Mizutani, Tetsuya; Kurane, Ichiro; Yamaguchi, Ryoji; Hasegawa, Hideki; Saijo, Masayuki; Komase, Katsuhiro; Morikawa, Shigeru; Takeda, Makoto

    2013-06-01

    A canine distemper virus (CDV) strain, CYN07-dV, associated with a lethal outbreak in monkeys, used human signaling lymphocyte activation molecule as a receptor only poorly but readily adapted to use it following a P541S substitution in the hemagglutinin protein. Since CYN07-dV had an intrinsic ability to use human nectin-4, the adapted virus became able to use both human immune and epithelial cell receptors, as well as monkey and canine ones, suggesting that CDV can potentially infect humans.

  8. Inhibition of viral RNA synthesis in canine distemper virus infection by proanthocyanidin A2.

    PubMed

    Gallina, Laura; Dal Pozzo, Fabiana; Galligioni, Viola; Bombardelli, Ezio; Scagliarini, Alessandra

    2011-12-01

    Canine distemper virus (CDV) is a contagious and multisystemic viral disease that affects domestic and wild canines as well as other terrestrial and aquatic carnivores. The disease in dogs is often fatal and no specific antiviral therapy is currently available. In this study, we evaluated the in vitro antiviral activity against CDV of proanthocyanidin A2 (PA2), a phenolic dimer belonging to the class of condensed tannins present in plants. Our results showed that PA2 exerted in vitro antiviral activity against CDV with a higher selectivity index compared to ribavirin, included in our study for the previously tested anti-CDV activity. The time of addition assay led us to observe that PA2 was able to decrease the viral RNA synthesis and to reduce progeny virus liberation, at different times post infection suggesting multiple mechanisms of action including inhibition of viral replicative complex and modulation of the redox milieu. These data suggest that PA2, isolated from the bark of Aesculus hippocastanum, has potential usefulness as an anti-CDV compound inhibiting viral replication.

  9. Prevalence of antibodies to canine parvovirus and distemper virus in wolves in the Canadian Rocky Mountains.

    PubMed

    Nelson, Brynn; Hebblewhite, Mark; Ezenwa, Vanessa; Shury, Todd; Merrill, Evelyn H; Paquet, Paul C; Schmiegelow, Fiona; Seip, Dale; Skinner, Geoff; Webb, Nathan

    2012-01-01

    Wild carnivores are often exposed to diseases via contact with peridomestic host species that travel through the wildland-urban interfaces. To determine the antibody prevalences and relationships to human activity for two common canid pathogens, we sampled 99 wolves (Canis lupus) from 2000 to 2008 for antibodies to canine parvovirus (CPV) and canine distemper virus (CDV) in Banff and Jasper National Parks and surrounding areas of the Canadian Rockies. This population was the source for wolves reintroduced into the Northern Rockies of the US. Of 99 wolves sampled, 94 had detectable antibody to CPV (95%), 24 were antibody-positive for CDV (24%), and 24 had antibodies to both pathogens (24%). We tested whether antibody prevalences for CPV and CDV were higher closer to human activity (roads, town sites, First Nation reserves) and as a function of sex and age class. Wolves ≥2 yr old were more likely to be have antibodies to CPV. For CDV, male wolves, wolves ≥2 yr, and those closer to First Nation reserves were more likely to have antibodies. Overall, however, we found minimal support for human influence on antibody prevalence for CDV and CPV. The similarity between our antibody prevalence results and results from recent studies in Yellowstone National Park suggests that at least in the case of CDV, and perhaps CPV, these could be important pathogens with potential effects on wolf populations.

  10. Detection of canine distemper virus in blood samples by reverse transcription loop-mediated isothermal amplification.

    PubMed

    Cho, H S; Park, N Y

    2005-11-01

    Reverse transcription loop-mediated isothermal amplification (RT-LAMP) was used to detect canine distemper virus (CDV) genomic RNA. A set of four primers, two outer and two inner, were designed from CDV genomic RNA targeting the nucleocapsid protein gene. The optimal reaction time and temperature for LAMP were determined to be 60 min at 65 degrees C. The relative sensitivity and specificity of RT-LAMP was found to be 100% and 93.3%, respectively, based on 50 canine blood samples and using RT-PCR as the gold standard. The detection limit of the RT-LAMP method was 100 times lower than with RT-PCR (10-1TCID50 ml(-1) versus 10TCID50 ml(-1)). In addition to the advantage resulting from the visual detection of the end-product, the LAMP method is fast, requiring only 1 h to complete the assay. The LAMP method is a viable alternative to RT-PCR for diagnosing CDV infection in dogs. The LAMP method might be useful as an on site diagnostic assay for detecting CDV.

  11. Canine distemper virus epithelial cell infection is required for clinical disease but not for immunosuppression.

    PubMed

    Sawatsky, Bevan; Wong, Xiao-Xiang; Hinkelmann, Sarah; Cattaneo, Roberto; von Messling, Veronika

    2012-04-01

    To characterize the importance of infection of epithelial cells for morbillivirus pathogenesis, we took advantage of the severe disease caused by canine distemper virus (CDV) in ferrets. To obtain a CDV that was unable to enter epithelial cells but retained the ability to enter immune cells, we transferred to its attachment (H) protein two mutations shown to interfere with the interaction of measles virus H with its epithelial receptor, human nectin-4. As expected for an epithelial receptor (EpR)-blind CDV, this virus infected dog and ferret epithelial cells inefficiently and did not cause cell fusion or syncytium formation. On the other hand, the EpR-blind CDV replicated in cells expressing canine signaling lymphocyte activation molecule (SLAM), the morbillivirus immune cell receptor, with similar kinetics to those of wild-type CDV. While ferrets infected with wild-type CDV died within 12 days after infection, after developing severe rash and fever, animals infected with the EpR-blind virus showed no clinical signs of disease. Nevertheless, both viruses spread rapidly and efficiently in immune cells, causing similar levels of leukopenia and inhibition of lymphocyte proliferation activity, two indicators of morbillivirus immunosuppression. Infection was documented for airway epithelia of ferrets infected with wild-type CDV but not for those of animals infected with the EpR-blind virus, and only animals infected with wild-type CDV shed virus. Thus, epithelial cell infection is necessary for clinical disease and efficient virus shedding but not for immunosuppression.

  12. Fatal canine distemper infection in a pack of African wild dogs in the Serengeti ecosystem, Tanzania.

    PubMed

    Goller, Katja V; Fyumagwa, Robert D; Nikolin, Veljko; East, Marion L; Kilewo, Morris; Speck, Stephanie; Müller, Thomas; Matzke, Martina; Wibbelt, Gudrun

    2010-12-15

    In 2007, disease related mortality occurred in one African wild dog (Lycaon pictus) pack close to the north-eastern boundary of the Serengeti National Park, Tanzania. Histopathological examination of tissues from six animals revealed that the main pathologic changes comprised interstitial pneumonia and suppurative to necrotizing bronchopneumonia. Respiratory epithelial cells contained numerous eosinophilic intracytoplasmic inclusion bodies and multiple syncytial cells were found throughout the parenchymal tissue, both reacting clearly positive with antibodies against canine distemper virus (CDV) antigen. Phylogenetic analysis based on a 388 nucleotide (nt) fragment of the CDV phosphoprotein (P) gene revealed that the pack was infected with a CDV variant most closely related to Tanzanian variants, including those obtained in 1994 during a CDV epidemic in the Serengeti National Park and from captive African wild dogs in the Mkomazi Game Reserve in 2000. Phylogenetic analysis of a 335-nt fragment of the fusion (F) gene confirmed that the pack in 2007 was infected with a variant most closely related to one variant from 1994 during the epidemic in the Serengeti National Park from which a comparable fragment is available. Screening of tissue samples for concurrent infections revealed evidence of canine parvovirus, Streptococcus equi subsp. ruminatorum and Hepatozoon sp. No evidence of infection with Babesia sp. or rabies virus was found. Possible implications of concurrent infections are discussed. This is the first molecular characterisation of CDV in free-ranging African wild dogs and only the third confirmed case of fatal CDV infection in a free-ranging pack.

  13. Expression of canine distemper virus receptor nectin-4 in the central nervous system of dogs.

    PubMed

    Pratakpiriya, Watanyoo; Ping Teh, Angeline Ping; Radtanakatikanon, Araya; Pirarat, Nopadon; Thi Lan, Nguyen; Takeda, Makoto; Techangamsuwan, Somporn; Yamaguchi, Ryoji

    2017-03-23

    Canine distemper virus (CDV) exhibits lymphotropic, epitheliotropic, and neurotropic nature, and causes a severe systemic infection in susceptible animals. Initially, signaling lymphocyte activation molecule (SLAM) expressed on immune cells has been identified as a crucial cellular receptor for CDV. Currently, nectin-4 expressed in epithelia has been shown to be another receptor for CDV. Our previous study demonstrated that neurons express nectin-4 and are infected with CDV. In this study, we investigated the distribution pattern of nectin-4 in various cell types in the canine central nervous system and showed its relation to CDV infection to further clarify the pathology of disease. Histopathological, immunohistochemical and immunofluorescent analyses were done using formalin-fixed paraffin-embedded tissues of CDV-infected dogs. Dual staining of nectin-4 and CDV antigen or nectin-4 and brain cell markers was performed. Nectin-4 was detected in ependymal cells, epithelia of choroid plexus, meningeal cells, neurons, granular cells, and Purkinje's cells. CDV antigens were detected in these nectin-4-positive cells, further suggesting contribution of nectin-4 for the CDV neurovirulence. On the other hand, astrocytes did not express nectin-4, although they were frequently infected with CDV. Since astrocytes are negative for SLAM expression, they must express an unidentified CDV receptor, which also contributes to CDV neurovirulence.

  14. Application of a dot enzyme-linked immunosorbent assay for evaluation of the immune status to canine parvovirus and distemper virus in adult dogs before revaccination.

    PubMed

    Waner, Trevor; Mazar, Shlomit; Keren-Kornblatt, Ephraim

    2006-05-01

    A growing body of literature has been published indicating that the current practice of annual vaccination of dogs may not be beneficial and in some cases may even be harmful. A number of publications have proposed assessing the immune status of dogs before annual revaccination. In this study the usefulness of a commercially available dot-ELISA kit was evaluated to determine the duration IgG antibody titers to canine parvovirus (CPV) and canine distemper virus (CDV) in 158 dogs vaccinated at least one year ago. Overall, the percentage of dogs with protective antibody titers to both CPV and CDV was 84%. The percentage of dogs with borderline antibody titers was 11% for CPV and 10% for CDV. Four percent of the dogs had no detectable antibody to CPV and 6% had no antibody to CDV. The results reported here are in good agreement with other studies measuring IgG antibody levels. It is concluded that the kit offers veterinarians the opportunity of determining antibody titers and revaccinating only those pets whose antibody titers to specific diseases have waned.

  15. Phylogenetic analysis of the haemagglutinin gene of canine distemper virus strains detected from breeding foxes, raccoon dogs and minks in China.

    PubMed

    Zhao, Jian-Jun; Yan, Xi-Jun; Chai, Xiu-Li; Martella, Vito; Luo, Guo-Liang; Zhang, Hai-Ling; Gao, Han; Liu, Ying-Xue; Bai, Xue; Zhang, Lei; Chen, Tao; Xu, Lei; Zhao, Chun-Fei; Wang, Feng-Xue; Shao, Xi-Qun; Wu, Wei; Cheng, Shi-Peng

    2010-01-06

    Canine distemper virus (CDV) infects a variety of carnivores, including wild and domestic Canidae. Genetic/antigenic heterogeneity has been observed among the various CDV strains, notably in the haemagglutinin (H) gene, that appears as a good target to gather epidemiological information. Based on sequence analysis of the H gene, wild-type CDV strains cluster into distinct geographic lineages (genotypes), irrespective of the species of isolation. The sequence of the H gene of 28 CDV strains detected from both vaccinated and non-vaccinated breeding foxes, raccoon dogs and minks from different geographical areas of China during the years 2004-2008 was determined. All the CDV strains but two (strains HL and HLJ2) were characterized as Asia-1 genotype and were highly similar to each other (96.2-99.7% at the amino acid [aa] level) and to other Asia-1 strains (96.1-99.5% aa) previously detected in China. The CDV strains HL and HLJ2 were both collected from foxes in Heilongjiang province in 2005. Strain HL resembled CDVs of the Arctic genotype (GR88-like) and displayed high aa identity (98.0%) to the Chinese canine strain Liu. By converse, strain HLJ2 was barely related to CDVs of the Asia-2 genotype (88.7-90.3% aa identity), and could represent a novel CDV genotype, tentatively proposed as Asia-3. These results suggest that at least three different CDV genotypes, distantly related (81.8-91.6% aa identity) to the vaccine strains, Onderstepoort-like (America-1 genotype), are currently circulating in breeding foxes, raccoon dogs and minks in China, and that the genotype Asia-1 is predominant. Whether the diversity between wild-type CDVs and the vaccine strains may affect, to some extent, the efficacy of the vaccines deserves further investigations.

  16. Identification of Amino Acid Substitutions with Compensational Effects in the Attachment Protein of Canine Distemper Virus

    PubMed Central

    Sattler, Ursula; Khosravi, Mojtaba; Avila, Mislay; Pilo, Paola; Langedijk, Johannes P.; Ader-Ebert, Nadine; Alves, Lisa A.; Plattet, Philippe

    2014-01-01

    ABSTRACT The hemagglutinin (H) gene of canine distemper virus (CDV) encodes the receptor-binding protein. This protein, together with the fusion (F) protein, is pivotal for infectivity since it contributes to the fusion of the viral envelope with the host cell membrane. Of the two receptors currently known for CDV (nectin-4 and the signaling lymphocyte activation molecule [SLAM]), SLAM is considered the most relevant for host susceptibility. To investigate how evolution might have impacted the host-CDV interaction, we examined the functional properties of a series of missense single nucleotide polymorphisms (SNPs) naturally accumulating within the H-gene sequences during the transition between two distinct but related strains. The two strains, a wild-type strain and a consensus strain, were part of a single continental outbreak in European wildlife and occurred in distinct geographical areas 2 years apart. The deduced amino acid sequence of the two H genes differed at 5 residues. A panel of mutants carrying all the combinations of the SNPs was obtained by site-directed mutagenesis. The selected mutant, wild type, and consensus H proteins were functionally evaluated according to their surface expression, SLAM binding, fusion protein interaction, and cell fusion efficiencies. The results highlight that the most detrimental functional effects are associated with specific sets of SNPs. Strikingly, an efficient compensational system driven by additional SNPs appears to come into play, virtually neutralizing the negative functional effects. This system seems to contribute to the maintenance of the tightly regulated function of the H-gene-encoded attachment protein. IMPORTANCE To investigate how evolution might have impacted the host-canine distemper virus (CDV) interaction, we examined the functional properties of naturally occurring single nucleotide polymorphisms (SNPs) in the hemagglutinin gene of two related but distinct strains of CDV. The hemagglutinin gene encodes

  17. Identification of amino acid substitutions with compensational effects in the attachment protein of canine distemper virus.

    PubMed

    Sattler, Ursula; Khosravi, Mojtaba; Avila, Mislay; Pilo, Paola; Langedijk, Johannes P; Ader-Ebert, Nadine; Alves, Lisa A; Plattet, Philippe; Origgi, Francesco C

    2014-07-01

    The hemagglutinin (H) gene of canine distemper virus (CDV) encodes the receptor-binding protein. This protein, together with the fusion (F) protein, is pivotal for infectivity since it contributes to the fusion of the viral envelope with the host cell membrane. Of the two receptors currently known for CDV (nectin-4 and the signaling lymphocyte activation molecule [SLAM]), SLAM is considered the most relevant for host susceptibility. To investigate how evolution might have impacted the host-CDV interaction, we examined the functional properties of a series of missense single nucleotide polymorphisms (SNPs) naturally accumulating within the H-gene sequences during the transition between two distinct but related strains. The two strains, a wild-type strain and a consensus strain, were part of a single continental outbreak in European wildlife and occurred in distinct geographical areas 2 years apart. The deduced amino acid sequence of the two H genes differed at 5 residues. A panel of mutants carrying all the combinations of the SNPs was obtained by site-directed mutagenesis. The selected mutant, wild type, and consensus H proteins were functionally evaluated according to their surface expression, SLAM binding, fusion protein interaction, and cell fusion efficiencies. The results highlight that the most detrimental functional effects are associated with specific sets of SNPs. Strikingly, an efficient compensational system driven by additional SNPs appears to come into play, virtually neutralizing the negative functional effects. This system seems to contribute to the maintenance of the tightly regulated function of the H-gene-encoded attachment protein. Importance: To investigate how evolution might have impacted the host-canine distemper virus (CDV) interaction, we examined the functional properties of naturally occurring single nucleotide polymorphisms (SNPs) in the hemagglutinin gene of two related but distinct strains of CDV. The hemagglutinin gene encodes the

  18. Rabies virus and canine distemper virus in wild and domestic carnivores in Northern Kenya: are domestic dogs the reservoir?

    PubMed

    Prager, K C; Mazet, Jonna A K; Dubovi, Edward J; Frank, Laurence G; Munson, Linda; Wagner, Aaron P; Woodroffe, Rosie

    2012-12-01

    Rabies virus (RV) and canine distemper virus (CDV) can cause significant mortality in wild carnivore populations, and RV threatens human lives. We investigated serological patterns of exposure to CDV and RV in domestic dogs (Canis familiaris), African wild dogs (Lycaon pictus), black-backed jackals (Canis mesomelas), spotted hyenas (Crocuta crocuta), striped hyenas (Hyaena hyaena) and African lions (Panthera leo), over a 10-year period, in a Kenyan rangeland to assess the role domestic dogs may play in the transmission dynamics of these two important canid pathogens. Observed patterns of RV exposure suggested that repeated introduction, rather than maintenance, occurred in the wild carnivore species studied. However, RV appeared to have been maintained in domestic dogs: exposure was more likely in domestic dogs than in the wild carnivores; was detected consistently over time without variation among years; and was detected in juveniles (≤1-year-old) as well as adults (>1-year-old). We conclude that this domestic dog population could be a RV reservoir. By contrast, the absence of evidence of CDV exposure for each carnivore species examined in the study area, for specific years, suggested repeated introduction, rather than maintenance, and that CDV may require a larger reservoir population than RV. This reservoir could be a larger domestic dog population; another wildlife species; or a "metareservoir" consisting of multiple interconnected carnivore populations. Our findings suggest that RV risks to people and wild carnivores might be controlled by domestic dog vaccination, but that CDV control, if required, would need to target the species of concern.

  19. Canine distemper virus infection among wildlife before and after the epidemic

    PubMed Central

    SUZUKI, Junko; NISHIO, Yohei; KAMEO, Yuki; TERADA, Yutaka; KUWATA, Ryusei; SHIMODA, Hiroshi; SUZUKI, Kazuo; MAEDA, Ken

    2015-01-01

    In 2007–2008, a canine distemper virus (CDV) epidemic occurred among wild animals in Wakayama Prefecture, Japan, and many mammals, including the wild boar and deer, were infected. In this study, CDV prevalence among wild animals was surveyed before and after the epidemic. At first, an enzyme-linked immunosorbent assay (ELISA) with horseradish peroxidase-conjugated protein A/G was established to detect CDV antibodies in many mammalian species. This established ELISA was available for testing dogs, raccoons and raccoon dogs as well as virus-neutralization test. Next, a serological survey of wild mammalians was conducted, and it was indicated that many wild mammalians, particularly raccoons, were infected with CDV during the epidemic, but few were infected before and after the epidemic. On the other hand, many raccoon dogs died during the epidemic, but CDV remained prevalent in the remaining population, and a small epidemic occurred in raccoon dogs in 2012–2013. These results indicated that the epidemic of 2007–2008 may have been intensified by transmission to raccoons. PMID:26074342

  20. CD9, a tetraspan transmembrane protein, renders cells susceptible to canine distemper virus.

    PubMed Central

    Löffler, S; Lottspeich, F; Lanza, F; Azorsa, D O; ter Meulen, V; Schneider-Schaulies, J

    1997-01-01

    Canine distemper virus (CDV), a lymphotropic and neurotropic negative-stranded RNA virus of the Morbillivirus genus, causes a life-threatening disease in several carnivores, including domestic dogs. To identify the cellular receptor(s) involved in the uptake of CDV by susceptible cells, we isolated a monoclonal antibody (MAb K41) which binds to the cell surface and inhibits the CDV infection of several cell lines from various species. Pretreatment of cells with MAb K41 reduces the number of infectious centers and the size of the syncytia. Using affinity chromatography with MAb K41, we purified from HeLa and Vero cell extracts a 26-kDa protein which contained the amino acid sequence TKDEPQRETLK of human CD9, a member of the tetraspan transmembrane or transmembrane 4 superfamily of cell surface proteins. Transfection of NIH 3T3 or MDBK cells with a CD9 expression plasmid rendered these cells permissive for viral infection and raised virus production by a factor of 10 to 100. The mechanism involved is still unclear, since we were unable to detect direct binding of CDV to CD9 by using immunoprecipitation and a virus overlay protein binding assay. These findings indicate that human CD9 and its homologs in other species are necessary factors for the uptake of CDV by target cells, the formation of syncytia, and the production of progeny virus. PMID:8985321

  1. Canine distemper virus infection of primary hippocampal cells induces increase in extracellular glutamate and neurodegeneration.

    PubMed

    Brunner, Jean-Marc; Plattet, Philippe; Majcherczyk, Paul; Zurbriggen, Andreas; Wittek, Riccardo; Hirling, Harald

    2007-11-01

    The canine distemper virus (CDV) belongs to the Morbillivirus genus which includes important human pathogens like the closely related measles virus. CDV infection can reach the nervous system where it causes serious malfunctions. Although this pathology is well described, the molecular events in brain infection are still poorly understood. Here we studied infection in vitro by CDV using a model of dissociated cell cultures from newborn rat hippocampus. We used a recombinant CDV closely related to the neurovirulent A75/17 which also expresses the enhanced green fluorescent protein. We found that infected neurons and astrocytes could be clearly detected, and that infection spreads only slowly to neighboring cells. Interestingly, this infection causes a massive cell death of neurons, which includes also non-infected neurons. Antagonists of NMDA-type or alpha-amino-3-hydroxy-5-methylisoxazole-4-propinate (AMPA)-type glutamate receptors could slow down this neuron loss, indicating an involvement of the glutamatergic system in the induction of cell death in infected and non-infected cells. Finally, we show that, following CDV infection, there is a steady increase in extracellular glutamate in infected cultures. These results indicate that CDV infection induces excitotoxic insults on neurons via glutamatergic signaling.

  2. Natural infection with canine distemper virus in hand-feeding Rhesus monkeys in China.

    PubMed

    Sun, Zhaozeng; Li, Aixue; Ye, Huahu; Shi, Yansheng; Hu, Zhongming; Zeng, Lin

    2010-03-24

    An outbreak of canine distemper virus (CDV) in hand-feeding Rhesus monkeys in China was reported. Twenty Rhesus monkeys presented blood and mucus in feces, respiratory symptoms, anorexia, acute fever, thicken of footpad and red rashes in the faces over 1-month period. CDV infection was identified by characteristic clinical signs, the specific detection of the BIT Rapid color CDV detection kit, electron microscopy and the results of sequence aligning. A phylogenetic analysis further confirmed that the CDV in the Rhesus monkeys belonged to the clade of the epidemic CDV types of China. All the infected monkeys were monitored and treated with antiserum therapy. The antiserum therapy seemed more effective for adult monkeys than young monkeys. Twelve monkeys died. The high mortality might indicate that the virulence of CDV to monkeys was enhanced. This is the first report we are aware of documenting Rhesus monkeys infected with CDV in China. Urgent work should be done to prevent the possibly epidemic of CDV in non-human primate.

  3. Amino-terminal precursor sequence modulates canine distemper virus fusion protein function.

    PubMed

    von Messling, Veronika; Cattaneo, Roberto

    2002-05-01

    The fusion (F) proteins of most paramyxoviruses are classical type I glycoproteins with a short hydrophobic leader sequence closely following the translation initiation codon. The predicted reading frame of the canine distemper virus (CDV) F protein is more complex, with a short hydrophobic sequence beginning 115 codons downstream of the first AUG. To verify if the sequence between the first AUG and the hydrophobic region is translated, we produced a specific antiserum that indeed detected a short-lived F protein precursor that we named PreF(0). A peptide resulting from PreF(0) cleavage was identified and named Pre, and its half-life was measured to be about 30 min. PreF(0) cleavage was completed before proteolytic activation of F(0) into its F(1) and F(2) subunits by furin. To test the hypothesis that the Pre peptide may influence protein activity, we compared the function of F proteins synthesized with that peptide to that of F proteins synthesized with a shorter amino-terminal signal sequence. F proteins synthesized with the Pre peptide were more stable and less active. Thus, the Pre peptide modulates the function of the CDV F protein. Interestingly, a distinct two-hit activation process has been recently described for human respiratory syncytial virus, another paramyxovirus.

  4. Canine distemper virus uses both the anterograde and the hematogenous pathway for neuroinvasion.

    PubMed

    Rudd, Penny A; Cattaneo, Roberto; von Messling, Veronika

    2006-10-01

    Canine distemper virus (CDV), a member of the Morbillivirus genus that also includes measles virus, frequently causes neurologic complications, but the routes and timing of CDV invasion of the central nervous system (CNS) are poorly understood. To characterize these events, we cloned and sequenced the genome of a neurovirulent CDV (strain A75/17) and produced an infectious cDNA that expresses the green fluorescent protein. This virus fully retained its virulence in ferrets: the course and signs of disease were equivalent to those of the parental isolate. We observed CNS invasion through two distinct pathways: anterogradely via the olfactory nerve and hematogenously through the choroid plexus and cerebral blood vessels. CNS invasion only occurred after massive infection of the lymphatic system and spread to the epithelial cells throughout the body. While at early time points, mostly immune and endothelial cells were infected, the virus later spread to glial cells and neurons. Together, the results suggest similarities in the timing, target cells, and CNS invasion routes of CDV, members of the Morbillivirus genus, and even other neurovirulent paramyxoviruses like Nipah and mumps viruses.

  5. Antiviral efficacy of EICAR against canine distemper virus (CDV) in vitro.

    PubMed

    Dal Pozzo, Fabiana; Galligioni, Viola; Vaccari, Francesca; Gallina, Laura; Battilani, Mara; Scagliarini, Alessandra

    2010-04-01

    Canine distemper virus (CDV) is a highly contagious pathogen of carnivores. In dogs, the disease is characterized by high lethality rates and no specific antiviral therapy is available. The aim of this study was to verify the in vitro antiviral activity of the 5-ethynyl-1-beta-d-ribofuranosylimidazole-4-carboxamide (EICAR) and to compare it with the 1-(beta-d-ribofuranosyl)-1,2,4-triazole-3-carboxamide (ribavirin, RBV). EICAR was more active than RBV against CDV replication, while both molecules exhibited low selectivity indexes. A reversal of their antiviral activity was observed after addition of guanosine, suggesting their involvement in the inhibition of the inosine monophosphate dehydrogenase enzyme (IMPDH). RBV and EICAR had a time- and concentration-dependent anti-CDV activity, mainly displayed during the first 10h post-infection. The involvement of the inhibition of the viral RNA-dependent RNA polymerase (vRdRp) is discussed, as well as the role of CDV as a model to study more potent and selective antiviral molecules active against other Paramyxoviridae.

  6. Immunohistochemical investigation of cerebellum in dogs infected with canine distemper virus.

    PubMed

    Kabakci, Nalan; Yarim, M; Karahan, S; Guvenc, T; Yagci, B B; Gurcan, I S

    2004-01-01

    The cerebella of 21 dogs with canine distemper virus (CDV) infection and four normal dogs were examined histopathologically and immunohistochemically. Cerebella of CDV-infected dogs showed nonsuppurative demyelinating encephalomyelitis, classified as acute, subacute or chronic. Immunolocalisation of CDV antigen also confirmed the infection. Tissues were examined for co-localisation of the CDV antigen with either an astrocyte-specific marker, glial fibrillary acidic protein (GFAP), or an oligodendrocyte-specific marker, galactocerebroside (GalC). Immunoreactive cells were counted in demyelinating areas of the white matter. The number of astrocytes (GFAP positive) was significantly (p < 0.05) higher in CDV-infected dogs compared to controls. In contrast, the number of oligodendrocytes (GalC positive) was significantly (p < 0.001) lower in CDV-infected dogs and was much lower in chronic cases (p < 0.05). Approximately 41% of astrocytes and 17% of oligodendrocytes were immunoreactive for CDV. The ratio of CDV-infected oligodendrocytes and astrocytes remained almost constant during the progression of the disease (P > 0.05). In conclusion, CDV infects both astrocytes and oligodendrocytes. The gradual loss of oligodendrocytes is most likely responsible for the progressive demyelination in CDV infection. Astrocytosis in CDV infection should be further investigated if it occurs to stimulate oligodendrocytes for myelin production to compensate for the loss or to induce oligodendrocyte degeneration.

  7. Canine distemper in an isolated population of fishers (Martes pennanti) from California.

    PubMed

    Keller, Stefan M; Gabriel, Mourad; Terio, Karen A; Dubovi, Edward J; VanWormer, Elizabeth; Sweitzer, Rick; Barret, Reginald; Thompson, Craig; Purcell, Kathryn; Munson, Linda

    2012-10-01

    Four fishers (Martes pennanti) from an insular population in the southern Sierra Nevada Mountains, California, USA died as a consequence of an infection with canine distemper virus (CDV) in 2009. Three fishers were found in close temporal and spatial relationship; the fourth fisher died 4 mo later at a 70 km distance from the initial group. Gross lesions were restricted to hyperkeratosis of periocular skin and ulceration of footpads. All animals had necrotizing bronchitis and bronchiolitis with syncytia and intracytoplasmic inclusion bodies. Inclusion bodies were abundant in the epithelia of urinary bladder and epididymis but were infrequent in the renal pelvis and the female genital epithelia. No histopathologic or immunohistochemical evidence for virus spread to the central nervous system was found. One fisher had encephalitis caused by Sarcocystis neurona and another had severe head trauma as a consequence of predation. The H gene nucleotide sequence of the virus isolates from the first three fishers was identical and was 99.6% identical to the isolate from the fourth fisher. Phylogenetically, the isolates clustered with other North American isolates separate from classical European wildlife lineage strains. These data suggest that the European wildlife lineage might consist of two separate subgroups that are genetically distinct and endemic in different geographic regions. The source of infection as well as pertinent transmission routes remained unclear. This is the first report of CDV in fishers and underscores the significance of CDV as a pathogen of management concern.

  8. Relation of clinical signs to pathological changes in 19 cases of canine distemper encephalomyelitis.

    PubMed

    Koutinas, A F; Polizopoulou, Z S; Baumgaertner, W; Lekkas, S; Kontos, V

    2002-01-01

    In an attempt to associate the clinical neurological syndromes with the neuropathological features of canine distemper (CD), 19 spontaneous cases with neurological involvement were examined, before and after euthanasia. Seventeen dogs were less than one year of age and all except two (89.4%) were unvaccinated against CD. Various extraneural signs associated with CD encephalomyelitis (CDE) were seen in 15 dogs. Generalized or localized myoclonus was the most common sign observed (13/19). Seventeen of the dogs presented with signs suggestive of one neuroanatomical location of lesions. Of these animals, seven had signs of cerebral, two of cerebellar, four of cervical, one of cervicothoracic, two of thoracolumbar and two of lumbosacral syndrome. The diagnosis of CD was confirmed immunohistochemically (detection of CD viral antigen), serologically (neutralizing serum antibody titre > or = 16) and histopathologically (CDV inclusion bodies, type of central nervous system lesions). An association of the neuroanatomical lesion location and the histopathological findings was noted in 14 out of 17 dogs (82.3%). Myoclonus could be attributed to lower motor neuron damage in eight out of 13 dogs (61.5%).

  9. Antibody titers against canine distemper virus in unvaccinated rural dogs from Ahvaz, Iran.

    PubMed

    Avizeh, R; Shapouri, M R Seyfiabad; Akhlaghi, N

    2007-11-01

    The purpose of this study was to evaluate the prevalence of antibodies to Canine Distemper Virus (CDV) in unvaccinated rural dogs without known immunization status and to assess risk factors for infection by means of indirect immunofluorescent assay (IFA), in Ahvaz district, southwest of Iran. Serum samples were randomly collected from 97 healthy dogs 6 months and older from villages around Ahvaz city between 2004 and 2005. Dogs were grouped by age and sex to determine whether these factors were associated with antibody titers, using Fisher's exact test. Seroprevalence to CDV antibodies in these dogs were 17.52% indicating that this virus is present in the ecosystem. Also there is evidence of previous natural exposure to CDV. Prevalence of antibodies to CDV did not differ between sexes or ages. Rural dogs are abundant in the ecosystem of area and interact with other species of wild carnivores and domestic animals in ways that could encourage disease transmission. Therefore the role of rural dogs in the epizootiology of CDV in both urban dogs and wildlife needs to be further explored.

  10. An immunochromatography assay for rapid antemortem diagnosis of dogs suspected to have canine distemper.

    PubMed

    An, Dong-Jun; Kim, Tae-Young; Song, Dae-Sub; Kang, Bo-Kyu; Park, Bong-Kyun

    2008-02-01

    A new assay was developed for rapid and antemortem diagnosis of canine distemper (CD). This immunochromatography (IC)-based assay, which employs two monoclonal anti-CDV antibodies, was compared with nested PCR. When serial dilutions of purified CDV were tested, the CDV detection limits of the nested PCR and IC assays were 2 x 10(2)TCID(50)/ml and 5 x 10(2)TCID(50)/ml, respectively. Nasal irrigation fluid, conjunctival swabs, and blood lymphocytes from 66 dogs suspected to have CD were tested. Preliminary IC experiments revealed that the optimal sample volume and reaction time were 100 microl and 5 min, respectively. Relative to nested PCR, the sensitivity and specificity of the IC assay was maximal (100% and 100%, respectively) when conjunctival swabs were tested. This is significant because conjunctival swab specimens are easy to obtain in the early phase of CD infection. However, with blood lymphocytes and nasal samples, the IC assay was slightly less sensitive (89.7% and 85.7%, respectively) and specific (94.6% and 100%, respectively) than nested PCR. Since this novel IC assay does not require special instruments, it is a simple enough for dog owners to use. Since early detection of CD would allow appropriate treatment and quarantine to be instituted quickly, such a test would help reduce the morbidity and mortality associated with CD help to prevent its spread to other animals.

  11. Canine distemper virus as a threat to wild tigers in Russia and across their range.

    PubMed

    Gilbert, Martin; Soutyrina, Svetlana V; Seryodkin, Ivan V; Sulikhan, Nadezhda; Uphyrkina, Olga V; Goncharuk, Mikhail; Matthews, Louise; Cleaveland, Sarah; Miquelle, Dale G

    2015-07-01

    Canine distemper virus (CDV) has recently been identified in populations of wild tigers in Russia and India. Tiger populations are generally too small to maintain CDV for long periods, but are at risk of infections arising from more abundant susceptible hosts that constitute a reservoir of infection. Because CDV is an additive mortality factor, it could represent a significant threat to small, isolated tiger populations. In Russia, CDV was associated with the deaths of tigers in 2004 and 2010, and was coincident with a localized decline of tigers in Sikhote-Alin Biosphere Zapovednik (from 25 tigers in 2008 to 9 in 2012). Habitat continuity with surrounding areas likely played an important role in promoting an ongoing recovery. We recommend steps be taken to assess the presence and the impact of CDV in all tiger range states, but should not detract focus away from the primary threats to tigers, which include habitat loss and fragmentation, poaching and retaliatory killing. Research priorities include: (i) recognition and diagnosis of clinical cases of CDV in tigers when they occur; and (ii) collection of baseline data on the health of wild tigers. CDV infection of individual tigers need not imply a conservation threat, and modeling should complement disease surveillance and targeted research to assess the potential impact to tiger populations across the range of ecosystems, population densities and climate extremes occupied by tigers. Describing the role of domestic and wild carnivores as contributors to a local CDV reservoir is an important precursor to considering control measures.

  12. Canine distemper virus infection among wildlife before and after the epidemic.

    PubMed

    Suzuki, Junko; Nishio, Yohei; Kameo, Yuki; Terada, Yutaka; Kuwata, Ryusei; Shimoda, Hiroshi; Suzuki, Kazuo; Maeda, Ken

    2015-11-01

    In 2007-2008, a canine distemper virus (CDV) epidemic occurred among wild animals in Wakayama Prefecture, Japan, and many mammals, including the wild boar and deer, were infected. In this study, CDV prevalence among wild animals was surveyed before and after the epidemic. At first, an enzyme-linked immunosorbent assay (ELISA) with horseradish peroxidase-conjugated protein A/G was established to detect CDV antibodies in many mammalian species. This established ELISA was available for testing dogs, raccoons and raccoon dogs as well as virus-neutralization test. Next, a serological survey of wild mammalians was conducted, and it was indicated that many wild mammalians, particularly raccoons, were infected with CDV during the epidemic, but few were infected before and after the epidemic. On the other hand, many raccoon dogs died during the epidemic, but CDV remained prevalent in the remaining population, and a small epidemic occurred in raccoon dogs in 2012-2013. These results indicated that the epidemic of 2007-2008 may have been intensified by transmission to raccoons.

  13. Molecular phylogeography of canine distemper virus: Geographic origin and global spreading.

    PubMed

    Panzera, Yanina; Sarute, Nicolás; Iraola, Gregorio; Hernández, Martín; Pérez, Ruben

    2015-11-01

    Canine distemper virus (CDV) (Paramyxoviridae-Morbillivirus) is a worldwide spread virus causing a fatal systemic disease in a broad range of carnivore hosts. In this study we performed Bayesian inferences using 208 full-length hemagglutinin gene nucleotide sequences isolated in 16 countries during 37 years (1975-2011). The estimated time to the most recent common ancestor suggested that current CDV strains emerged in the United States in the 1880s. This ancestor diversified through time into two ancestral clades, the current America 1 lineage that recently spread to Asia, and other ancestral clade that diversified and spread worldwide to originate the remaining eight lineages characterized to date. The spreading of CDV was characterized by several migratory events with posterior local differentiation, and expansion of the virus host range. A significant genetic flow between domestic and wildlife hosts is displayed; being domestic hosts the main viral reservoirs worldwide. This study is an extensive and integrative description of spatio/temporal population dynamics of CDV lineages that provides a novel evolutionary paradigm about the origin and dissemination of the current strains of the virus.

  14. Lethal canine distemper virus outbreak in cynomolgus monkeys in Japan in 2008.

    PubMed

    Sakai, Kouji; Nagata, Noriyo; Ami, Yasushi; Seki, Fumio; Suzaki, Yuriko; Iwata-Yoshikawa, Naoko; Suzuki, Tadaki; Fukushi, Shuetsu; Mizutani, Tetsuya; Yoshikawa, Tomoki; Otsuki, Noriyuki; Kurane, Ichiro; Komase, Katsuhiro; Yamaguchi, Ryoji; Hasegawa, Hideki; Saijo, Masayuki; Takeda, Makoto; Morikawa, Shigeru

    2013-01-01

    Canine distemper virus (CDV) has recently expanded its host range to nonhuman primates. A large CDV outbreak occurred in rhesus monkeys at a breeding farm in Guangxi Province, China, in 2006, followed by another outbreak in rhesus monkeys at an animal center in Beijing in 2008. In 2008 in Japan, a CDV outbreak also occurred in cynomolgus monkeys imported from China. In that outbreak, 46 monkeys died from severe pneumonia during a quarantine period. A CDV strain (CYN07-dV) was isolated in Vero cells expressing dog signaling lymphocyte activation molecule (SLAM). Phylogenic analysis showed that CYN07-dV was closely related to the recent CDV outbreaks in China, suggesting continuing chains of CDV infection in monkeys. In vitro, CYN07-dV uses macaca SLAM and macaca nectin4 as receptors as efficiently as dog SLAM and dog nectin4, respectively. CYN07-dV showed high virulence in experimentally infected cynomolgus monkeys and excreted progeny viruses in oral fluid and feces. These data revealed that some of the CDV strains, like CYN07-dV, have the potential to cause acute systemic infection in monkeys.

  15. Sandwich-dot enzyme-linked immunosorbent assay for the detection of canine distemper virus.

    PubMed

    Li, Zhi; Zhang, Yanlong; Wang, Huiguo; Jin, Jinhua; Li, Wenzhe

    2013-10-01

    A sandwich-dot enzyme-linked immunosorbent assay (dot ELISA) was developed for the detection of canine distemper virus (CDV). In 56 dogs suspected to have CD the rates of detection of CDV antigen in samples of blood lymphocytes and palpebral conjunctiva by dot ELISA and ELISA were, respectively, 91% (49/54) and 81% (44/54) for the lymphocyte samples and 88% (28/32) and 75% (24/32) for the conjunctival samples. The CDV detection limits were 10 ng/50 μL for dot ELISA and 40 ng/50 μL for ELISA. The reliability of dot ELISA relative to electron microscopy was 96% with 22 samples: all 21 samples in which CDV particles were observed by electron microscopy yielded positive results with dot ELISA; the single sample in which particles were not observed yielded false-positive results with dot ELISA. The results indicate that the dot ELISA developed can serve as a reliable rapid diagnostic test in suspected cases of CD and also be useful for epidemiologic surveillance of the disease.

  16. Propagation of Asian isolates of canine distemper virus (CDV) in hamster cell lines

    PubMed Central

    Sultan, Serageldeen; Lan, Nguyen Thi; Ueda, Toshiki; Yamaguchi, Ryoji; Maeda, Ken; Kai, Kazushige

    2009-01-01

    Backgrounds The aim of this study was to confirm the propagation of various canine distemper viruses (CDV) in hamster cell lines of HmLu and BHK, since only a little is known about the possibility of propagation of CDV in rodent cells irrespective of their epidemiological importance. Methods The growth of CDV in hamster cell lines was monitored by titration using Vero.dogSLAMtag (Vero-DST) cells that had been proven to be susceptible to almost all field isolates of CDV, with the preparations of cell-free and cell-associated virus from the cultures infected with recent Asian isolates of CDV (13 strains) and by observing the development of cytopathic effect (CPE) in infected cultures of hamster cell lines. Results Eleven of 13 strains grew in HmLu cells, and 12 of 13 strains grew in BHK cells with apparent CPE of cell fusion in the late stage of infection. Two strains and a strain of Asia 1 group could not grow in HmLu cells and BHK cells, respectively. Conclusion The present study demonstrates at the first time that hamster cell lines can propagate the majority of Asian field isolates of CDV. The usage of two hamster cell lines suggested to be useful to characterize the field isolates biologically. PMID:19835588

  17. Infectious Progression of Canine Distemper Virus from Circulating Cerebrospinal Fluid into the Central Nervous System

    PubMed Central

    Takenaka, Akiko; Sato, Hiroki; Ikeda, Fusako; Yoneda, Misako

    2016-01-01

    ABSTRACT In the current study, we generated recombinant chimeric canine distemper viruses (CDVs) by replacing the hemagglutinin (H) and/or phosphoprotein (P) gene in an avirulent strain expressing enhanced green fluorescent protein (EGFP) with those of a mouse-adapted neurovirulent strain. An in vitro experimental infection indicated that the chimeric CDVs possessing the H gene derived from the mouse-adapted CDV acquired infectivity for neural cells. These cells lack the CDV receptors that have been identified to date (SLAM and nectin-4), indicating that the H protein defines infectivity in various cell lines. The recombinant viruses were administered intracerebrally to 1-week-old mice. Fatal neurological signs of disease were observed only with a recombinant CDV that possessed both the H and P genes of the mouse-adapted strain, similar to the parental mouse-adapted strain, suggesting that both genes are important to drive virulence of CDV in mice. Using this recombinant CDV, we traced the intracerebral propagation of CDV by detecting EGFP. Widespread infection was observed in the cerebral hemispheres and brainstems of the infected mice. In addition, EGFP fluorescence in the brain slices demonstrated a sequential infectious progression in the central nervous system: CDV primarily infected the neuroependymal cells lining the ventricular wall and the neurons of the hippocampus and cortex adjacent to the ventricle, and it then progressed to an extensive infection of the brain surface, followed by the parenchyma and cortex. In the hippocampal formation, CDV spread in a unidirectional retrograde pattern along neuronal processes in the hippocampal formation from the CA1 region to the CA3 region and the dentate gyrus. Our mouse model demonstrated that the main target cells of CDV are neurons in the acute phase and that the virus spreads via neuronal transmission pathways in the hippocampal formation. IMPORTANCE CDV is the etiological agent of distemper in dogs and other

  18. Viral infectivity and intracellular distribution of matrix (M) protein of canine distemper virus are affected by actin filaments.

    PubMed

    Klauschies, F; Gützkow, T; Hinkelmann, S; von Messling, V; Vaske, B; Herrler, G; Haas, L

    2010-09-01

    To investigate the role of cytoskeletal components in canine distemper virus (CDV) replication, various agents were used that interfere with turnover of actin filaments and microtubules. Only inhibition of actin filaments significantly reduced viral infectivity. Analysis of the intracellular localization of the viral matrix (M) protein revealed that it aligned along actin filaments. Treatment with actin filament-disrupting drugs led to a marked intracellular redistribution of M protein during infection as well as transfection. In contrast, the localization of the CDV fusion (F) protein was not significantly changed during transfection. Thus, a M protein-actin filament interaction appears to be important for generation of infectious CDV.

  19. Efficient isolation of wild strains of canine distemper virus in Vero cells expressing canine SLAM (CD150) and their adaptability to marmoset B95a cells.

    PubMed

    Seki, Fumio; Ono, Nobuyuki; Yamaguchi, Ryoji; Yanagi, Yusuke

    2003-09-01

    We have previously shown that canine signaling lymphocyte activation molecule (SLAM; also known as CD150) acts as a cellular receptor for canine distemper virus (CDV). In this study, we established Vero cells stably expressing canine SLAM (Vero.DogSLAMtag cells). Viruses were isolated in Vero.DogSLAMtag cells one day after inoculation with spleen samples from five out of seven dogs with distemper. By contrast, virus isolation with reportedly sensitive marmoset B95a cells was only successful from three diseased animals at 7 to 10 days after inoculation, and no virus was recovered from any dogs when Vero cells were used for isolation. The CDV strain isolated in Vero.DogSLAMtag cells did not cause cytopathic effects in B95a and human SLAM-expressing Vero cells, whereas the strain isolated in B95a cells from the same dog did so in canine or human SLAM-expressing Vero cells as well as B95a cells. There were two amino acid differences in the hemagglutinin sequence between these strains. Cell fusion analysis after expression of envelope proteins and vesicular stomatitis virus pseudotype assay showed that their hemagglutinins were responsible for the difference in cell tropism between them. Site-directed mutagenesis indicated that glutamic acid to lysine substitution at position 530 of the hemagglutinin was required for the adaptation to the usage of marmoset SLAM. Our results indicate that Vero cells stably expressing canine SLAM are highly sensitive to CDV in clinical specimens and that only a single amino acid substitution in the hemagglutinin can allow the virus to adapt to marmoset SLAM.

  20. Intranasal vaccine trial for canine infectious tracheobronchitis (kennel cough).

    PubMed

    Glickman, L T; Appel, M J

    1981-08-01

    Two field trials were conducted during periods of endemic (summer) and epizootic (winter) canine infectious tracheobronchitis activity to evaluate the efficacy of three intranasal vaccines in a closed commercial beagle breeding kennel. A trivalent vaccine containing Bordetella bronchiseptica, canine parainfluenza, and canine adenovirus-2 was administered at 3 weeks of age. The vaccine was 71.2% and 81.8% effective in decreasing the incidence of coughing during the winter and summer trials, respectively. The number of deaths was lower in each of the vaccine groups than in the placebo groups. No adverse reactions were observed with any of the intranasal vaccines.

  1. Canine Distemper Virus Fusion Activation: Critical Role of Residue E123 of CD150/SLAM

    PubMed Central

    Khosravi, Mojtaba; Bringolf, Fanny; Röthlisberger, Silvan; Bieringer, Maria; Schneider-Schaulies, Jürgen; Zurbriggen, Andreas; Origgi, Francesco

    2015-01-01

    ABSTRACT Measles virus (MeV) and canine distemper virus (CDV) possess tetrameric attachment proteins (H) and trimeric fusion proteins, which cooperate with either SLAM or nectin 4 receptors to trigger membrane fusion for cell entry. While the MeV H-SLAM cocrystal structure revealed the binding interface, two distinct oligomeric H assemblies were also determined. In one of the conformations, two SLAM units were sandwiched between two discrete H head domains, thus spotlighting two binding interfaces (“front” and “back”). Here, we investigated the functional relevance of both interfaces in activating the CDV membrane fusion machinery. While alanine-scanning mutagenesis identified five critical regulatory residues in the front H-binding site of SLAM, the replacement of a conserved glutamate residue (E at position 123, replaced with A [E123A]) led to the most pronounced impact on fusion promotion. Intriguingly, while determination of the interaction of H with the receptor using soluble constructs revealed reduced binding for the identified SLAM mutants, no effect was recorded when physical interaction was investigated with the full-length counterparts of both molecules. Conversely, although mutagenesis of three strategically selected residues within the back H-binding site of SLAM did not substantially affect fusion triggering, nevertheless, the mutants weakened the H-SLAM interaction recorded with the membrane-anchored protein constructs. Collectively, our findings support a mode of binding between the attachment protein and the V domain of SLAM that is common to all morbilliviruses and suggest a major role of the SLAM residue E123, located at the front H-binding site, in triggering the fusion machinery. However, our data additionally support the hypothesis that other microdomain(s) of both glycoproteins (including the back H-binding site) might be required to achieve fully productive H-SLAM interactions. IMPORTANCE A complete understanding of the measles virus

  2. Canine distemper virus in the Serengeti ecosystem: molecular adaptation to different carnivore species.

    PubMed

    Nikolin, Veljko M; Olarte-Castillo, Ximena A; Osterrieder, Nikolaus; Hofer, Heribert; Dubovi, Edward; Mazzoni, Camila J; Brunner, Edgar; Goller, Katja V; Fyumagwa, Robert D; Moehlman, Patricia D; Thierer, Dagmar; East, Marion L

    2016-12-07

    Was the 1993/1994 fatal canine distemper virus (CDV) epidemic in lions and spotted hyaenas in the Serengeti ecosystem caused by the recent spillover of a virulent domestic dog strain or one well adapted to these noncanids? We examine this question using sequence data from 13 'Serengeti' strains including five complete genomes obtained between 1993 and 2011. Phylogenetic and haplotype network analyses reveal that strains from noncanids during the epidemic were more closely related to each other than to those from domestic or wild canids. All noncanid 'Serengeti' strains during the epidemic encoded: (1) one novel substitution G134S in the CDV-V protein; and (2) the rare amino acid combination 519I/549H at two sites under positive selection in the region of the CDV-H protein that binds to SLAM (CD 150) host cell receptors. Worldwide, only a few noncanid strains in the America II lineage encode CDV-H 519I/549H. All canid 'Serengeti' strains during the epidemic coded CDV-V 134G, and CDV-H 519R/549Y, or 519R/549H. A functional assay of cell entry revealed the highest performance by CDV-H proteins encoding 519I/549H in cells expressing lion SLAM receptors, and the highest performance by proteins encoding 519R/549Y, typical of dog strains worldwide, in cells expressing dog SLAM receptors. Our findings are consistent with an epidemic in lions and hyaenas caused by CDV variants better adapted to noncanids than canids, but not with the recent spillover of a dog strain. Our study reveals a greater complexity of CDV molecular epidemiology in multihost environments than previously thought.

  3. A molecular study of hippocampus in dogs with convulsion during canine distemper virus encephalitis.

    PubMed

    D'Intino, Giulia; Vaccari, Francesca; Sivilia, Sandra; Scagliarini, Alessandra; Gandini, Gualtiero; Giardino, Luciana; Calzà, Laura

    2006-07-07

    In this study, we have investigated the expression of the nuclear transcription factor (c-Fos, NFkB), growth factors (nerve growth factor--NGF, brain-derived neurotrophic factor--BDNF), peptides (enkephalin, galanin) and glutamate transporter (AA 504-523 rat EAAC1) in 6 dogs sacrificed immediately after seizure attack during encephalomyelitis due to canine distemper virus (CDV) (as assessed by clinical examination, RT-PCR and viral RNA detection either in blood or brain tissue and CDV immunohistochemistry in brain slices). In all these CDV affected dogs, the observed neurological signs included untreatable seizures, leading to cluster seizure activity and status epilepticus. In the inter-ictal phase abnormal mentation, postural and gait deficits and sometimes involuntary movements such as myoclonus were recorded. The same investigation was carried out in 5 control dogs affected by different disorders, all characterized by the absence of seizures. Brains were dissected out immediately after euthanasia and fixed; sections collected from the dorsal hippocampus were processed for immunohistochemistry. By comparing hippocampus sections obtained from dog with and without seizure, the following regulations were observed. A strong up-regulation of glutamate transporter throughout the cell layers was found together with the onset of nuclear Fos and NFkB-IR in the pyramidal cell layer X. Among the investigated peptides, we observed a slight increase in enkephalinergic fibers and a strong up-regulation of mu-opioid receptors, whereas galanin-IR seemed to be weaker. Finally, both NGF and BDNF expression was strongly up-regulated. BDNF-IR was mainly localized in the apical dendrite in pyramidal neurons. To our knowledge, these data offer the first indication that molecular events described in experimental kindling also occur during spontaneous pathology in animal species sharing close similarities to human neuropathology.

  4. Molecular Determinants Defining the Triggering Range of Prefusion F Complexes of Canine Distemper Virus

    PubMed Central

    Avila, Mislay; Alves, Lisa; Khosravi, Mojtaba; Ader-Ebert, Nadine; Origgi, Francesco; Schneider-Schaulies, Jürgen; Zurbriggen, Andreas; Plemper, Richard K.

    2014-01-01

    ABSTRACT The morbillivirus cell entry machinery consists of a fusion (F) protein trimer that refolds to mediate membrane fusion following receptor-induced conformational changes in its binding partner, the tetrameric attachment (H) protein. To identify molecular determinants that control F refolding, we generated F chimeras between measles virus (MeV) and canine distemper virus (CDV). We located a central pocket in the globular head domain of CDV F that regulates the stability of the metastable, prefusion conformational state of the F trimer. Most mutations introduced into this “pocket'” appeared to mediate a destabilizing effect, a phenotype associated with enhanced membrane fusion activity. Strikingly, under specific triggering conditions (i.e., variation of receptor type and H protein origin), some F mutants also exhibited resistance to a potent morbillivirus entry inhibitor, which is known to block F triggering by enhancing the stability of prefusion F trimers. Our data reveal that the molecular nature of the F stimulus and the intrinsic stability of metastable prefusion F both regulate the efficiency of F refolding and escape from small-molecule refolding blockers. IMPORTANCE With the aim to better characterize the thermodynamic basis of morbillivirus membrane fusion for cell entry and spread, we report here that the activation energy barrier of prefusion F trimers together with the molecular nature of the triggering “stimulus” (attachment protein and receptor types) define a “triggering range,” which governs the initiation of the membrane fusion process. A central “pocket” microdomain in the globular F head contributes substantially to the regulation of the conformational stability of the prefusion complexes. The triggering range also defines the mechanism of viral escape from entry inhibitors and describes how the cellular environment can affect membrane fusion efficiency. PMID:24371057

  5. Transcriptional Changes in Canine Distemper Virus-Induced Demyelinating Leukoencephalitis Favor a Biphasic Mode of Demyelination

    PubMed Central

    Ulrich, Reiner; Puff, Christina; Wewetzer, Konstantin; Kalkuhl, Arno; Deschl, Ulrich; Baumgärtner, Wolfgang

    2014-01-01

    Canine distemper virus (CDV)-induced demyelinating leukoencephalitis in dogs (Canis familiaris) is suggested to represent a naturally occurring translational model for subacute sclerosing panencephalitis and multiple sclerosis in humans. The aim of this study was a hypothesis-free microarray analysis of the transcriptional changes within cerebellar specimens of five cases of acute, six cases of subacute demyelinating, and three cases of chronic demyelinating and inflammatory CDV leukoencephalitis as compared to twelve non-infected control dogs. Frozen cerebellar specimens were used for analysis of histopathological changes including demyelination, transcriptional changes employing microarrays, and presence of CDV nucleoprotein RNA and protein using microarrays, RT-qPCR and immunohistochemistry. Microarray analysis revealed 780 differentially expressed probe sets. The dominating change was an up-regulation of genes related to the innate and the humoral immune response, and less distinct the cytotoxic T-cell-mediated immune response in all subtypes of CDV leukoencephalitis as compared to controls. Multiple myelin genes including myelin basic protein and proteolipid protein displayed a selective down-regulation in subacute CDV leukoencephalitis, suggestive of an oligodendrocyte dystrophy. In contrast, a marked up-regulation of multiple immunoglobulin-like expressed sequence tags and the delta polypeptide of the CD3 antigen was observed in chronic CDV leukoencephalitis, in agreement with the hypothesis of an immune-mediated demyelination in the late inflammatory phase of the disease. Analysis of pathways intimately linked to demyelination as determined by morphometry employing correlation-based Gene Set Enrichment Analysis highlighted the pathomechanistic importance of up-regulated genes comprised by the gene ontology terms “viral replication” and “humoral immune response” as well as down-regulated genes functionally related to “metabolite and energy

  6. Epidemiology, pathology, and genetic analysis of a canine distemper epidemic in Namibia.

    PubMed

    Gowtage-Sequeira, Sonya; Banyard, Ashley C; Barrett, Tom; Buczkowski, Hubert; Funk, Stephan M; Cleaveland, Sarah

    2009-10-01

    Severe population declines have resulted from the spillover of canine distemper virus (CDV) into susceptible wildlife, with both domestic and wild canids being involved in the maintenance and transmission of the virus. This study (March 2001 to October 2003) collated case data, serologic, pathologic, and molecular data to describe the spillover of CDV from domestic dogs (Canis familiaris) to black-backed jackals (Canis mesomelas) during an epidemic on the Namibian coast. Antibody prevalence in jackals peaked at 74.1%, and the clinical signs and histopathologic observations closely resembled those observed in domestic dog cases. Viral RNA was isolated from the brain of a domestic dog from the outbreak area. Sequence data from the phosphoprotein (P) gene and the hemagglutinin (H) genes were used for phylogenetic analyses. The P gene sequence from the domestic dog shared 98% identity with the sequence data available for other CDV isolates of African carnivores. For the H gene, the two sequences available from the outbreak that decimated the lion population in Tanzania in 1994 were the closest match with the Namibian sample, being 94% identical across 1,122 base pairs (bp). Phylogenetic analyses based on this region clustered the Namibian sample with the CDV that is within the morbilliviruses. This is the first description of an epidemic involving black-backed jackals in Namibia, demonstrating that this species has the capacity for rapid and large-scale dissemination of CDV. This work highlights the threat posed to endangered wildlife in Namibia by the spillover of CDV from domestic dog populations. Very few sequence data are currently available for CDV isolates from African carnivores, and this work provides the first sequence data from a Namibian CDV isolate.

  7. Viral oncolysis - can insights from measles be transferred to canine distemper virus?

    PubMed

    Lapp, Stefanie; Pfankuche, Vanessa M; Baumgärtner, Wolfgang; Puff, Christina

    2014-06-11

    Neoplastic diseases represent one of the most common causes of death among humans and animals. Currently available and applied therapeutic options often remain insufficient and unsatisfactory, therefore new and innovative strategies and approaches are highly needed. Periodically, oncolytic viruses have been in the center of interest since the first anecdotal description of their potential usefulness as an anti-tumor treatment concept. Though first reports referred to an incidental measles virus infection causing tumor regression in a patient suffering from lymphoma several decades ago, no final treatment concept has been developed since then. However, numerous viruses, such as herpes-, adeno- and paramyxoviruses, have been investigated, characterized, and modified with the aim to generate a new anti-cancer treatment option. Among the different viruses, measles virus still represents a highly interesting candidate for such an approach. Numerous different tumors of humans including malignant lymphoma, lung and colorectal adenocarcinoma, mesothelioma, and ovarian cancer, have been studied in vitro and in vivo as potential targets. Moreover, several concepts using different virus preparations are now in clinical trials in humans and may proceed to a new treatment option. Surprisingly, only few studies have investigated viral oncolysis in veterinary medicine. The close relationship between measles virus (MV) and canine distemper virus (CDV), both are morbilliviruses, and the fact that numerous tumors in dogs exhibit similarities to their human counterpart, indicates that both the virus and species dog represent a highly interesting translational model for future research in viral oncolysis. Several recent studies support such an assumption. It is therefore the aim of the present communication to outline the mechanisms of morbillivirus-mediated oncolysis and to stimulate further research in this potentially expanding field of viral oncolysis in a highly suitable

  8. Canine Distemper Virus: an Emerging Disease in Wild Endangered Amur Tigers (Panthera tigris altaica)

    PubMed Central

    Seimon, Tracie A.; Miquelle, Dale G.; Chang, Tylis Y.; Newton, Alisa L.; Korotkova, Irina; Ivanchuk, Galina; Lyubchenko, Elena; Tupikov, Andre; Slabe, Evgeny; McAloose, Denise

    2013-01-01

    ABSTRACT Fewer than 500 Amur tigers (Panthera tigris altaica) remain in the wild. Due to low numbers and their solitary and reclusive nature, tiger sightings across their range in the Russian Far East and China are rare; sightings of sick tigers are rarer still. Serious neurologic disease observed in several wild tigers since 2001 suggested disease emergence in this endangered species. To investigate this possibility, histology, immunohistochemistry (IHC), in situ hybridization (ISH), and reverse transcription-PCR (RT-PCR) were performed on tissues from 5 affected tigers that died or were destroyed in 2001, 2004, or 2010. Our results reveal canine distemper virus (CDV) infection as the cause of neurologic disease in two tigers and definitively establish infection in a third. Nonsuppurative encephalitis with demyelination, eosinophilic nuclear viral inclusions, and positive immunolabeling for CDV by IHC and ISH were present in the two tigers with available brain tissue. CDV phosphoprotein (P) and hemagglutinin (H) gene products were obtained from brains of these two tigers by RT-PCR, and a short fragment of CDV P gene sequence was detected in lymph node tissue of a third tiger. Phylogenetically, Amur tiger CDV groups with an Arctic-like strain in Baikal seals (Phoca siberica). Our results, which include mapping the location of positive tigers and recognition of a cluster of cases in 2010, coupled with a lack of reported CDV antibodies in Amur tigers prior to 2000 suggest wide geographic distribution of CDV across the tiger range and recent emergence of CDV as a significant infectious disease threat to endangered Amur tigers in the Russian Far East. PMID:23943758

  9. Climate extremes promote fatal co-infections during canine distemper epidemics in African lions.

    PubMed

    Munson, Linda; Terio, Karen A; Kock, Richard; Mlengeya, Titus; Roelke, Melody E; Dubovi, Edward; Summers, Brian; Sinclair, Anthony R E; Packer, Craig

    2008-06-25

    Extreme climatic conditions may alter historic host-pathogen relationships and synchronize the temporal and spatial convergence of multiple infectious agents, triggering epidemics with far greater mortality than those due to single pathogens. Here we present the first data to clearly illustrate how climate extremes can promote a complex interplay between epidemic and endemic pathogens that are normally tolerated in isolation, but with co-infection, result in catastrophic mortality. A 1994 canine distemper virus (CDV) epidemic in Serengeti lions (Panthera leo) coincided with the death of a third of the population, and a second high-mortality CDV epidemic struck the nearby Ngorongoro Crater lion population in 2001. The extent of adult mortalities was unusual for CDV and prompted an investigation into contributing factors. Serological analyses indicated that at least five "silent" CDV epidemics swept through the same two lion populations between 1976 and 2006 without clinical signs or measurable mortality, indicating that CDV was not necessarily fatal. Clinical and pathology findings suggested that hemoparsitism was a major contributing factor during fatal epidemics. Using quantitative real-time PCR, we measured the magnitude of hemoparasite infections in these populations over 22 years and demonstrated significantly higher levels of Babesia during the 1994 and 2001 epidemics. Babesia levels correlated with mortalities and extent of CDV exposure within prides. The common event preceding the two high mortality CDV outbreaks was extreme drought conditions with wide-spread herbivore die-offs, most notably of Cape buffalo (Syncerus caffer). As a consequence of high tick numbers after the resumption of rains and heavy tick infestations of starving buffalo, the lions were infected by unusually high numbers of Babesia, infections that were magnified by the immunosuppressive effects of coincident CDV, leading to unprecedented mortality. Such mass mortality events may become

  10. Transcriptional changes in canine distemper virus-induced demyelinating leukoencephalitis favor a biphasic mode of demyelination.

    PubMed

    Ulrich, Reiner; Puff, Christina; Wewetzer, Konstantin; Kalkuhl, Arno; Deschl, Ulrich; Baumgärtner, Wolfgang

    2014-01-01

    Canine distemper virus (CDV)-induced demyelinating leukoencephalitis in dogs (Canis familiaris) is suggested to represent a naturally occurring translational model for subacute sclerosing panencephalitis and multiple sclerosis in humans. The aim of this study was a hypothesis-free microarray analysis of the transcriptional changes within cerebellar specimens of five cases of acute, six cases of subacute demyelinating, and three cases of chronic demyelinating and inflammatory CDV leukoencephalitis as compared to twelve non-infected control dogs. Frozen cerebellar specimens were used for analysis of histopathological changes including demyelination, transcriptional changes employing microarrays, and presence of CDV nucleoprotein RNA and protein using microarrays, RT-qPCR and immunohistochemistry. Microarray analysis revealed 780 differentially expressed probe sets. The dominating change was an up-regulation of genes related to the innate and the humoral immune response, and less distinct the cytotoxic T-cell-mediated immune response in all subtypes of CDV leukoencephalitis as compared to controls. Multiple myelin genes including myelin basic protein and proteolipid protein displayed a selective down-regulation in subacute CDV leukoencephalitis, suggestive of an oligodendrocyte dystrophy. In contrast, a marked up-regulation of multiple immunoglobulin-like expressed sequence tags and the delta polypeptide of the CD3 antigen was observed in chronic CDV leukoencephalitis, in agreement with the hypothesis of an immune-mediated demyelination in the late inflammatory phase of the disease. Analysis of pathways intimately linked to demyelination as determined by morphometry employing correlation-based Gene Set Enrichment Analysis highlighted the pathomechanistic importance of up-regulated genes comprised by the gene ontology terms "viral replication" and "humoral immune response" as well as down-regulated genes functionally related to "metabolite and energy generation".

  11. Susceptibility of carnivore hosts to strains of canine distemper virus from distinct genetic lineages.

    PubMed

    Nikolin, Veljko M; Wibbelt, Gudrun; Michler, Frank-Uwe F; Wolf, Peter; East, Marion L

    2012-04-23

    Using the complete haemagglutinin (HA) gene and partial phosphoprotein (P) gene we investigated the genotype of canine distemper virus (CDV) strains recovered from two wildlife species in Mecklenburg-Vorpommern, Germany. Phylogenetic analyses demonstrated significant differences between the strains from raccoons Procyon lotor (family Procyonidae) obtained in 2007 and strains from red foxes Vulpes vulpes (family Canidae) obtained in 2008. The raccoon strains belonged to the CDV European wildlife lineage whereas the red fox strains belonged to the CDV Europe lineage. We combined our genetic sequence data with published data from 138 CDV stains worldwide to investigate the proposed importance of amino acid substitutions in the SLAM binding region of the CDV HA protein at position 530 (G/E to R/D/N) and 549 (Y to H) to the spread of domestic dog-adapted CDV strains to other carnivores. We found no evidence that amino acid 530 was strongly affected by host species. Rather, site 530 was conserved within CDV lineages, regardless of host species. Contrary to expectation, strains from non-dog hosts did not exhibit a bias towards the predicted substitution Y549H. Wild canid hosts were more frequently infected by strains with 549Y, a pattern similar to domestic dogs. Non-canid strains showed no significant bias towards either H or Y at site 549, although there was a trend towards 549H. Significant differences between the prevalence of 549Y and 549H in wild canid strains and non-canid strains suggests a degree of virus adaptation to these categories of host.

  12. [Immunohistochemical staining of the astrocytic expression of glial fibrillary acidic protein and vimentin in the central nervous system of dogs with canine distemper].

    PubMed

    Orsini, Heloísa; Bondan, Eduardo Fernandes; Sanchez, Melissa; Lallo, Maria Anete; Maiorka, Paulo César; Dagli, Maria Lúcia Zaidan; Graça, Dominguita Luthers

    2007-12-01

    Considering that many aspects involved in the pathogenesis of the central nervous system (CNS) demyelinating diseases are still poorly understood and that astrocytes seem to mediate such processes, this study analyzed the participation of astrocytes in the demyelinating processes of CNS by using immunohistochemical staining of two astrocytic proteins--glial fibrillary acidic protein (GFAP) and vimentin (VIM)--comparing samples of cerebellum and brainstem from eight dogs with canine distemper and from two healthy dogs, from different breeds and ages varying from 1 to 4 years old. Histological sections were submitted to the avidin-biotin-peroxidase indirect method of immunohistochemical staining (ABC) and the astrocytic reactivity, observed in light microscopy, was quantified in a computer system for image analysis. It was possible to notice, on most of the sections from sick animals, degenerative lesions that indicate demyelination. The immunostaining for GFAP and VIM was more intense on animals with canine distemper, specially around the ventricules and near degenerated sites. There was no significant difference between the immunostaining (GFAP and VIM) of animals with canine distemper with and without inflammatory infiltrate of the cerebellar white matter. The increased immunoreactivity of astrocytes for GFAP and the VIM reexpression in injured areas indicate the astrocytic involvement on nervous tissue response to the demyelinating lesions induced by the canine distemper virus (CDV) in the CNS.

  13. Broadly reactive pan-paramyxovirus reverse transcription polymerase chain reaction and sequence analysis for the detection of Canine distemper virus in a case of canine meningoencephalitis of unknown etiology

    PubMed Central

    Schatzberg, Scott J.; Li, Qiang; Porter, Brian F.; Barber, Renee M.; Claiborne, Mary Kate; Levine, Jonathan M.; Levine, Gwendolyn J.; Israel, Sarah K.; Young, Benjamin D.; Kiupel, Matti; Greene, Craig; Ruone, Susan; Anderson, Larry; Tong, Suxiang

    2016-01-01

    Despite the immunologic protection associated with routine vaccination protocols, Canine distemper virus (CDV) remains an important pathogen of dogs. Antemortem diagnosis of systemic CDV infection may be made by reverse transcription polymerase chain reaction (RT-PCR) and/or immunohistochemical testing for CDV antigen; central nervous system infection often requires postmortem confirmation via histopathology and immunohistochemistry. An 8-month-old intact male French Bulldog previously vaccinated for CDV presented with multifocal neurologic signs. Based on clinical and postmortem findings, the dog’s disease was categorized as a meningoencephalitis of unknown etiology. Broadly reactive, pan-paramyxovirus RT-PCR using consensus-degenerate hybrid oligonucleotide primers, combined with sequence analysis, identified CDV amplicons in the dog’s brain. Immunohistochemistry confirmed the presence of CDV antigens, and a specific CDV RT-PCR based on the phosphoprotein gene identified a wild-type versus vaccinal virus strain. This case illustrates the utility of broadly reactive PCR and sequence analysis for the identification of pathogens in diseases with unknown etiology. PMID:19901287

  14. A suspected canine distemper epidemic as the cause of a catastrophic decline in Santa Catalina Island foxes (Urocyon littoralis catalinae).

    PubMed

    Timm, Steven F; Munson, Linda; Summers, Brian A; Terio, Karen A; Dubovi, Edward J; Rupprecht, Charles E; Kapil, Sanjay; Garcelon, David K

    2009-04-01

    The island fox (Urocyon littoralis catalinae) population on Santa Catalina Island, California, USA declined precipitously in 1999 with an approximate 95% reduction on their eastern range, an area representing 87% of the island. During this investigation, between October 1999 and April 2000, evidence of live foxes dramatically decreased. The only carcass recovered during the decline succumbed to a co-infection of canine distemper virus (CDV) and toxoplasmosis. Sequence analysis of the viral P gene, derived by polymerase chain reaction, indicated that the virus was closely related to CDV from a mainland USA raccoon (Procyon lotor). Nine of 10 foxes trapped in 1999-2000, on the eastern portion of the island after the decline, had serologic evidence of exposure to CDV, whereas only four of 19 foxes trapped in this region in 1998 had antibodies reactive against CDV. The confirmation of CDV in one deceased fox, evidence of exposure to CDV in east-end foxes in 1999-2000 compared to 1998, and documentation of raccoon introductions to the island, implicates canine distemper as the cause of the population decline.

  15. Domestic dog origin of canine distemper virus in free-ranging wolves in Portugal as revealed by hemagglutinin gene characterization.

    PubMed

    Müller, Alexandra; Silva, Eliane; Santos, Nuno; Thompson, Gertrude

    2011-07-01

    Serologic evidence for canine distemper virus (CDV) has been described in grey wolves but, to our knowledge, virus strains circulating in wolves have not been characterized genetically. The emergence of CDV in several non-dog hosts has been associated with amino acid substitutions at sites 530 and 549 of the hemagglutinin (H) protein. We sequenced the H gene of wild-type canine distemper virus obtained from two free-ranging Iberian wolves (Canis lupus signatus) and from one domestic dog (Canis familiaris). More differences were found between the two wolf sequences than between one of the wolves (wolf 75) and the dog. The latter two had a very high nucleotide similarity resulting in identical H gene amino acid sequences. Possible explanations include geographic and especially temporal proximity of the CDV obtained from wolf 75 and the domestic dog, taken in 2007-2008, as opposed to that from wolf 3 taken more distantly in 1998. Analysis of the deduced amino acids of the viral hemagglutinin revealed a glycine (G) and a tyrosine (Y) at amino acid positions 530 and 549, respectively, of the partial signaling lymphocytic activation molecule (SLAM)-receptor binding region which is typically found in viral strains obtained from domestic dogs. This suggests that the CDV found in these wolves resulted from transmission events from local domestic dogs rather than from wildlife species.

  16. 9 CFR 113.214 - Parvovirus Vaccine, Killed Virus (Canine).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Parvovirus Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.214 Parvovirus Vaccine, Killed Virus (Canine). Parvovirus Vaccine... Master Seed which has been established as pure, safe, and immunogenic shall be used for...

  17. 9 CFR 113.214 - Parvovirus Vaccine, Killed Virus (Canine).

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Parvovirus Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.214 Parvovirus Vaccine, Killed Virus (Canine). Parvovirus Vaccine... Master Seed which has been established as pure, safe, and immunogenic shall be used for...

  18. 9 CFR 113.214 - Parvovirus Vaccine, Killed Virus (Canine).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Parvovirus Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.214 Parvovirus Vaccine, Killed Virus (Canine). Parvovirus Vaccine... Master Seed which has been established as pure, safe, and immunogenic shall be used for...

  19. 9 CFR 113.214 - Parvovirus Vaccine, Killed Virus (Canine).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Parvovirus Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.214 Parvovirus Vaccine, Killed Virus (Canine). Parvovirus Vaccine... Master Seed which has been established as pure, safe, and immunogenic shall be used for...

  20. 9 CFR 113.214 - Parvovirus Vaccine, Killed Virus (Canine).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Parvovirus Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.214 Parvovirus Vaccine, Killed Virus (Canine). Parvovirus Vaccine... Master Seed which has been established as pure, safe, and immunogenic shall be used for...

  1. A comparison of in situ hybridisation, reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ-RT-PCR for the detection of canine distemper virus RNA in Paget's disease.

    PubMed

    Hoyland, Judith A; Dixon, Janet A; Berry, Jacqueline L; Davies, Michael; Selby, Peter L; Mee, Andrew P

    2003-05-01

    Previous evidence implicating Paramyxoviruses in the aetiopathology of Paget's disease of bone has proved controversial. Whilst several groups have demonstrated Paramyxoviruses using techniques such as in situ hybridisation (ISH), reverse transcriptase-polymerase chain reaction (RT-PCR), and in situ-RT-PCR (IS-RT-PCR), others have found no evidence of viruses using only RT-PCR. To investigate this latter finding, we have now compared detection of canine distemper virus by ISH, RT-PCR (three different methods) and IS-RT-PCR, in 10 patients with Paget's disease, and samples of non-diseased bone from four patients. Canine distemper virus was detectable in six of the samples by ISH, but only in five of the samples by RT-PCR, using one of the methods. Neither of the other RT-PCR methods detected canine distemper virus. IS-RT-PCR demonstrated canine distemper virus in all 10 samples. There was no evidence of virus in the control samples. We have shown that the ability to detect canine distemper virus in bone is dependent on the technique used. IS-RT-PCR clearly showed that canine distemper virus was present in 100% of Pagetic samples, whereas canine distemper virus was only found in 60% by ISH and in 50% using one particular RT-PCR method. These results provide conclusive evidence that canine distemper virus is present within Pagetic bone, and provide a possible explanation for the failure of some groups to detect Paramyxovirus sequences. These findings also have wider implications for other studies investigating viral expression.

  2. Persistence of canine distemper virus in the Greater Yellowstone Ecosystem's carnivore community

    USGS Publications Warehouse

    Almberg, E.S.; Cross, P.C.; Smith, D.W.

    2010-01-01

    Canine distemper virus (CDV) is an acute, highly immunizing pathogen that should require high densities and large populations of hosts for long-term persistence, yet CDV persists among terrestrial carnivores with small, patchily distributed groups. We used CDV in the Greater Yellowstone ecosystem's (GYE) wolves (Canis lupus) and coyotes (Canis latrans) as a case study for exploring how metapopulation structure, host demographics, and multi-host transmission affect the critical community size and spatial scale required for CDV persistence. We illustrate how host spatial connectivity and demographic turnover interact to affect both local epidemic dynamics, such as the length and variation in inter-epidemic periods, and pathogen persistence using stochastic, spatially explicit susceptible-exposed-infectious-recovered simulation models. Given the apparent absence of other known persistence mechanisms (e.g., a carrier or environmental state, densely populated host, chronic infection, or a vector), we suggest that CDV requires either large spatial scales or multi-host transmission for persistence. Current GYE wolf populations are probably too small to support endemic CDV. Coyotes are a plausible reservoir host, but CDV would still require 50 000-100 000 individuals for moderate persistence (>50% over 10 years), which would equate to an area of 1-3 times the size of the GYE (60000-200000 km2). Coyotes, and carnivores in general, are not uniformly distributed; therefore, this is probably a gross underestimate of the spatial scale of CDV persistence. However, the presence of a second competent host species can greatly increase the probability of long-term CDV persistence at much smaller spatial scales. Although no management of CDV is currently recommended for the GYE, wolf managers in the region should expect periodic but unpredictable CDV-related population declines as often as every 2-5 years. Awareness and monitoring of such outbreaks will allow corresponding

  3. Persistence of canine distemper virus in the Greater Yellowstone ecosystem's carnivore community.

    PubMed

    Almberg, Emily S; Cross, Paul C; Smith, Douglas W

    2010-10-01

    Canine distemper virus (CDV) is an acute, highly immunizing pathogen that should require high densities and large populations of hosts for long-term persistence, yet CDV persists among terrestrial carnivores with small, patchily distributed groups. We used CDV in the Greater Yellowstone ecosystem's (GYE) wolves (Canis lupus) and coyotes (Canis latrans) as a case study for exploring how metapopulation structure, host demographics, and multi-host transmission affect the critical community size and spatial scale required for CDV persistence. We illustrate how host spatial connectivity and demographic turnover interact to affect both local epidemic dynamics, such as the length and variation in inter-epidemic periods, and pathogen persistence using stochastic, spatially explicit susceptible-exposed-infectious-recovered simulation models. Given the apparent absence of other known persistence mechanisms (e.g., a carrier or environmental state, densely populated host, chronic infection, or a vector), we suggest that CDV requires either large spatial scales or multi-host transmission for persistence. Current GYE wolf populations are probably too small to support endemic CDV. Coyotes are a plausible reservoir host, but CDV would still require 50000-100000 individuals for moderate persistence (> 50% over 10 years), which would equate to an area of 1-3 times the size of the GYE (60000-200000 km2). Coyotes, and carnivores in general, are not uniformly distributed; therefore, this is probably a gross underestimate of the spatial scale of CDV persistence. However, the presence of a second competent host species can greatly increase the probability of long-term CDV persistence at much smaller spatial scales. Although no management of CDV is currently recommended for the GYE, wolf managers in the region should expect periodic but unpredictable CDV-related population declines as often as every 2-5 years. Awareness and monitoring of such outbreaks will allow corresponding adjustments

  4. High prevalence of antibodies against canine adenovirus (CAV) type 2 in domestic dog populations in South Africa precludes the use of CAV-based recombinant rabies vaccines.

    PubMed

    Wright, N; Jackson, F R; Niezgoda, M; Ellison, J A; Rupprecht, C E; Nel, L H

    2013-08-28

    Rabies in dogs can be controlled through mass vaccination. Oral vaccination of domestic dogs would be useful in the developing world, where greater vaccination coverage is needed especially in inaccessible areas or places with large numbers of free-roaming dogs. From this perspective, recent research has focused on development of new recombinant vaccines that can be administered orally in a bait to be used as adjunct for parenteral vaccination. One such candidate, a recombinant canine adenovirus type 2 vaccine expressing the rabies virus glycoprotein (CAV2-RG), is considered a promising option for dogs, given host specificity and safety. To assess the potential use of this vaccine in domestic dog populations, we investigated the prevalence of antibodies against canine adenovirus type 2 in South African dogs. Blood was collected from 241 dogs from the Gauteng and KwaZulu-Natal provinces. Sampled dogs had not previously been vaccinated against canine adenovirus type 1 (CAV1) or canine adenovirus type 2 (CAV2). Animals from both provinces had a high percentage of seropositivity (45% and 62%), suggesting that CAV2 circulates extensively among domestic dog populations in South Africa. Given this finding, we evaluated the effect of pre-existing CAV-specific antibodies on the efficacy of the CAV2-RG vaccine delivered via the oral route in dogs. Purpose-bred Beagle dogs, which received prior vaccination against canine parvovirus, canine distemper virus and CAV, were immunized by oral administration of CAV2-RG. After rabies virus (RABV) infection all animals, except one vaccinated dog, developed rabies. This study demonstrated that pre-existing antibodies against CAV, such as naturally occurs in South African dogs, inhibits the development of neutralizing antibodies against RABV when immunized with a CAV-based rabies recombinant vaccine.

  5. Recombinant Canine Distemper Virus Strain Snyder Hill Expressing Green or Red Fluorescent Proteins Causes Meningoencephalitis in the Ferret

    PubMed Central

    Ludlow, M.; Nguyen, D. T.; Silin, D.; Lyubomska, O.; de Vries, R. D.; von Messling, V.; McQuaid, S.; De Swart, R. L.

    2012-01-01

    The propensity of canine distemper virus (CDV) to spread to the central nervous system is one of the primary features of distemper. Therefore, we developed a reverse genetics system based on the neurovirulent Snyder Hill (SH) strain of CDV (CDVSH) and show that this virus rapidly circumvents the blood-brain and blood-cerebrospinal fluid (CSF) barriers to spread into the subarachnoid space to induce dramatic viral meningoencephalitis. The use of recombinant CDVSH (rCDVSH) expressing enhanced green fluorescent protein (EGFP) or red fluorescent protein (dTomato) facilitated the sensitive pathological assessment of routes of virus spread in vivo. Infection of ferrets with these viruses led to the full spectrum of clinical signs typically associated with distemper in dogs during a rapid, fatal disease course of approximately 2 weeks. Comparison with the ferret-adapted CDV5804P and the prototypic wild-type CDVR252 showed that hematogenous infection of the choroid plexus is not a significant route of virus spread into the CSF. Instead, viral spread into the subarachnoid space in rCDVSH-infected animals was triggered by infection of vascular endothelial cells and the hematogenous spread of virus-infected leukocytes from meningeal blood vessels into the subarachnoid space. This resulted in widespread infection of cells of the pia and arachnoid mater of the leptomeninges over large areas of the cerebral hemispheres. The ability to sensitively assess the in vivo spread of a neurovirulent strain of CDV provides a novel model system to study the mechanisms of virus spread into the CSF and the pathogenesis of acute viral meningitis. PMID:22553334

  6. Recombinant canine distemper virus strain Snyder Hill expressing green or red fluorescent proteins causes meningoencephalitis in the ferret.

    PubMed

    Ludlow, M; Nguyen, D T; Silin, D; Lyubomska, O; de Vries, R D; von Messling, V; McQuaid, S; De Swart, R L; Duprex, W P

    2012-07-01

    The propensity of canine distemper virus (CDV) to spread to the central nervous system is one of the primary features of distemper. Therefore, we developed a reverse genetics system based on the neurovirulent Snyder Hill (SH) strain of CDV (CDV(SH)) and show that this virus rapidly circumvents the blood-brain and blood-cerebrospinal fluid (CSF) barriers to spread into the subarachnoid space to induce dramatic viral meningoencephalitis. The use of recombinant CDV(SH) (rCDV(SH)) expressing enhanced green fluorescent protein (EGFP) or red fluorescent protein (dTomato) facilitated the sensitive pathological assessment of routes of virus spread in vivo. Infection of ferrets with these viruses led to the full spectrum of clinical signs typically associated with distemper in dogs during a rapid, fatal disease course of approximately 2 weeks. Comparison with the ferret-adapted CDV(5804P) and the prototypic wild-type CDV(R252) showed that hematogenous infection of the choroid plexus is not a significant route of virus spread into the CSF. Instead, viral spread into the subarachnoid space in rCDV(SH)-infected animals was triggered by infection of vascular endothelial cells and the hematogenous spread of virus-infected leukocytes from meningeal blood vessels into the subarachnoid space. This resulted in widespread infection of cells of the pia and arachnoid mater of the leptomeninges over large areas of the cerebral hemispheres. The ability to sensitively assess the in vivo spread of a neurovirulent strain of CDV provides a novel model system to study the mechanisms of virus spread into the CSF and the pathogenesis of acute viral meningitis.

  7. Stability of canine distemper virus (CDV) after 20 passages in Vero-DST cells expressing the receptor protein for CDV.

    PubMed

    Lan, N T; Yamaguchi, R; Kawabata, A; Uchida, K; Kai, K; Sugano, S; Tateyama, S

    2006-12-20

    Isolates 007Lm, S124C and Ac96I and a Vero cell-adapted Onderstepoort strain of canine distemper viruses (CDV) were examined for stability after passages in Vero cells expressing the canine signaling lymphocyte activation molecule (dogSLAM, the intrinsic receptor to CDV). These viruses passage once in Vero cells expressing dogSLAM (Vero-DST) cells (original) and after 20 passages (20p) were compared by using sequence analyses and growth characteristics. All four strains of 20p grew well and were slightly better than their originals. The 20p viruses developed a cytopathic effect slightly lower than the original strains. A few changes in amino acids in the H gene were between the 20p and the original viruses, but the sites of changes were not specific. Fragments of P, M and L genes of all strains showed no nucleotide changes after the passages. These results showed that: (1) passages of CDVs in Vero-DST cells induced amino acid changes only in the H gene, not in the P, M and L genes, unlike in a previous study with Vero cells; (2) passages did not markedly affect the growth characteristics of every viral strain. These results indicate that Vero cells expressing canine SLAM allow the isolation and passaging of CDV without major changes in viral genes.

  8. Immunohistochemical distribution of alpha B-crystallin in the cerebellum of dogs infected with canine distemper virus.

    PubMed

    Guvenc, Tolga; Yarim, Murat; Gulbahar, Mustafa Yavuz; Kabak, Yonca B

    2008-03-01

    The cerebella of 12 dogs infected with canine distemper virus (CDV) and those of three normal dogs were examined. The avidin-biotin-peroxidase complex technique was used to detect alphaB-crystallin (alphaB-c) immunoreactivity and immunolocalisation of the CDV antigen. CDV antigens, immunopositive astrocytes, oligodendrocytes and granular neurons were seen in both the white and grey matter of the infected dogs. In the controls, alphaB-c immunopositive glial cells were seen in the white matter and around the Purkinje cells. In dogs with distemper, alphaB-c immunoreactivity was not observed in some of the glial cells around the Purkinje cells. A significant negative correlation of P < 0.01 level was found between areas of severe demyelination and the number of alphaB-c immunopositive cells in dogs infected with CDV. Such correlation was not observed between mild and moderate demyelinating areas and alphaB-c immunostaining. The alphaB-crystallin/ total number of cells ratio was found to be significant in severely affected demyelinating areas (P < 0.05). These data indicate that there was a relationship between the degrees of CDV associated with demyelination and the level of alphaB-c expression in the glial cells.

  9. Molecular detection of Canine distemper virus and the immunohistochemical characterization of the neurologic lesions in naturally occurring old dog encephalitis.

    PubMed

    Headley, Selwyn A; Amude, Alexandre M; Alfieri, Alice F; Bracarense, Ana Paula F R L; Alfieri, Amauri A; Summers, Brian A

    2009-09-01

    The current article describes a spontaneous case of old dog encephalitis (ODE) in a 7-year-old, intact, female Miniature Schnauzer dog from Londrina, Paraná, southern Brazil. Unlike conventional distemper encephalomyelitis, ODE is a poorly understood and extremely rare manifestation of Canine distemper virus (CDV) infection. The dog was presented with progressive clinical manifestations consistent with cerebral dysfunction. Briefly, histopathologic lesions were restricted to the forebrain and included chronic multifocal lymphoplasmacytic encephalitis with extensive perivascular cuffing, astrocytosis, and intranuclear inclusions within astrocytes and giant cells, with both intracytoplasmic and intranuclear inclusions. Immunohistochemistry (IHC) was used to identify the antigens of the nucleoprotein (NP) of CDV and to detect cluster of differentiation (CD)3, CD79a, macrophage (MAC) 387, glial fibrillary acidic protein, and vimentin to characterize the neuroparenchymal lesions. By IHC, CDV NP was demonstrated predominantly within neurons and astrocytes. Cells that formed perivascular cuffs and some astrocyte-like cells reacted intensely to vimentin. Reverse transcription polymerase chain reaction assay from brain sections further confirmed a role for CDV in this disease by the amplification and partial sequence analysis of the NP gene. These findings confirmed simultaneous detection of CDV in ODE by IHC and molecular assays. In addition, results of the current study could contribute to the neuropathologic characterization of this rare manifestation of CDV.

  10. Identification of key residues in virulent canine distemper virus hemagglutinin that control CD150/SLAM-binding activity.

    PubMed

    Zipperle, Ljerka; Langedijk, Johannes P M; Orvell, Claes; Vandevelde, Marc; Zurbriggen, Andreas; Plattet, Philippe

    2010-09-01

    Morbillivirus cell entry is controlled by hemagglutinin (H), an envelope-anchored viral glycoprotein determining interaction with multiple host cell surface receptors. Subsequent to virus-receptor attachment, H is thought to transduce a signal triggering the viral fusion glycoprotein, which in turn drives virus-cell fusion activity. Cell entry through the universal morbillivirus receptor CD150/SLAM was reported to depend on two nearby microdomains located within the hemagglutinin. Here, we provide evidence that three key residues in the virulent canine distemper virus A75/17 H protein (Y525, D526, and R529), clustering at the rim of a large recessed groove created by beta-propeller blades 4 and 5, control SLAM-binding activity without drastically modulating protein surface expression or SLAM-independent F triggering.

  11. Epitopes and nuclear localization analyses of canine distemper virus nucleocapsid protein by expression of its deletion mutants.

    PubMed

    Yoshida, E; Shin, Y S; Iwatsuki, K; Gemma, T; Miyashita, N; Tomonaga, K; Hirayama, N; Mikami, T; Kai, C

    1999-05-01

    A series of nucleocapsid protein (NP)-deleted genes of the Onderstepoort strain was constructed in order to locate antigenic regions of the NP of canine distemper virus. The expression of proteins from 5'-deleted NP genes was examined in COS-7 cells by indirect immunofluorescence assay using three monoclonal antibodies (MAbs), c-5, f-5 and h-6, and a rabbit serum against NP. These MAbs reacted with two regions of NP. Amino acid residues from 1 to 80, and 337-358, were necessary and sufficient for formation of the epitopes identified by MAbs f-5 and h-6, and c-5, respectively. The proteins translated from intact or 3'-deleted genes were found to be localized in the nuclei of COS-7 cells, whereas the proteins from the 5'-deleted genes were mainly detected in the cytoplasm. These results suggested that 80 amino acid residues at the N-terminus are required for transportation of NP into the nucleus.

  12. Canine distemper virus-associated encephalitis in free-living lynx (Lynx canadensis) and bobcats (Lynx rufus) of eastern Canada.

    PubMed

    Daoust, Pierre-Yves; McBurney, Scott R; Godson, Dale L; van de Bildt, Marco W G; Osterhaus, Albert D M E

    2009-07-01

    Between 1993 and 1999, encephalitis caused by morbillivirus was diagnosed by immunohistochemistry and histology in six lynx (Lynx canadensis) and one bobcat (Lynx rufus) in the eastern Canadian provinces of New Brunswick and Nova Scotia. Five of the six cases in lynx occurred within an 11-mo period in 1996-97. A second bobcat with encephalitis caused by unidentified protozoa and a nematode larva also had immunohistochemical evidence of neurologic infection by morbillivirus. The virus was identified as canine distemper virus (CDV) by reverse transcriptase polymerase chain reaction and nucleotide sequencing in four of five animals from which frozen tissue samples were available, and it was isolated in cell culture from one of them. To our knowledge, this is the first report of disease caused by CDV in free-living felids in North America.

  13. Molecular typing of canine distemper virus strains reveals the presence of a new genetic variant in South America.

    PubMed

    Sarute, Nicolás; Pérez, Ruben; Aldaz, Jaime; Alfieri, Amauri A; Alfieri, Alice F; Name, Daniela; Llanes, Jessika; Hernández, Martín; Francia, Lourdes; Panzera, Yanina

    2014-06-01

    Canine distemper virus (CDV, Paramyxoviridae, Morbillivirus) is the causative agent of a severe infectious disease affecting terrestrial and marine carnivores worldwide. Phylogenetic relationships and the genetic variability of the hemagglutinin (H) protein and the fusion protein signal-peptide (Fsp) allow for the classification of field strains into genetic lineages. Currently, there are nine CDV lineages worldwide, two of them co-circulating in South America. Using the Fsp-coding region, we analyzed the genetic variability of strains from Uruguay, Brazil, and Ecuador, and compared them with those described previously in South America and other geographical areas. The results revealed that the Brazilian and Uruguayan strains belong to the already described South America lineage (EU1/SA1), whereas the Ecuadorian strains cluster in a new clade, here named South America 3, which may represent the third CDV lineage described in South America.

  14. Canine distemper outbreak in raccoons suggests pathogen interspecies transmission amongst alien and native carnivores in urban areas from Germany.

    PubMed

    Rentería-Solís, Zaida; Förster, Christine; Aue, Angelika; Wittstatt, Ulrich; Wibbelt, Gudrun; König, Matthias

    2014-11-07

    From December 2012 to May 2013, an outbreak occurred among urban wild carnivores from Berlin. We collected 97 free-ranging raccoons from the city area. PCR assays, histopathology and immunohistochemistry confirmed canine distemper virus (CDV) infection in 74 raccoons. Phylogenetic analysis of haemagglutinin gene fragments (1767 nucleotides) of CDV isolated from four raccoons showed close relation to CDV isolates from foxes from Germany and a domestic dog from Hungary; all belonging to the "Europe" lineage of CDV. These study results suggest an inter-species transmission of CDV as the origin for the outbreak among the raccoon population. Implications for domestic pets and suggested interspecies transmission between urban wildlife and raccoons are discussed. This is the first major outbreak of CDV amongst free-ranging raccoons in Europe.

  15. Antagonistic pleiotropy and fitness trade-offs reveal specialist and generalist traits in strains of canine distemper virus.

    PubMed

    Nikolin, Veljko M; Osterrieder, Klaus; von Messling, Veronika; Hofer, Heribert; Anderson, Danielle; Dubovi, Edward; Brunner, Edgar; East, Marion L

    2012-01-01

    Theoretically, homogeneous environments favor the evolution of specialists whereas heterogeneous environments favor generalists. Canine distemper is a multi-host carnivore disease caused by canine distemper virus (CDV). The described cell receptor of CDV is SLAM (CD150). Attachment of CDV hemagglutinin protein (CDV-H) to this receptor facilitates fusion and virus entry in cooperation with the fusion protein (CDV-F). We investigated whether CDV strains co-evolved in the large, homogeneous domestic dog population exhibited specialist traits, and strains adapted to the heterogeneous environment of smaller populations of different carnivores exhibited generalist traits. Comparison of amino acid sequences of the SLAM binding region revealed higher similarity between sequences from Canidae species than to sequences from other carnivore families. Using an in vitro assay, we quantified syncytia formation mediated by CDV-H proteins from dog and non-dog CDV strains in cells expressing dog, lion or cat SLAM. CDV-H proteins from dog strains produced significantly higher values with cells expressing dog SLAM than with cells expressing lion or cat SLAM. CDV-H proteins from strains of non-dog species produced similar values in all three cell types, but lower values in cells expressing dog SLAM than the values obtained for CDV-H proteins from dog strains. By experimentally changing one amino acid (Y549H) in the CDV-H protein of one dog strain we decreased expression of specialist traits and increased expression of generalist traits, thereby confirming its functional importance. A virus titer assay demonstrated that dog strains produced higher titers in cells expressing dog SLAM than cells expressing SLAM of non-dog hosts, which suggested possible fitness benefits of specialization post-cell entry. We provide in vitro evidence for the expression of specialist and generalist traits by CDV strains, and fitness trade-offs across carnivore host environments caused by antagonistic

  16. Evaluation of ELISA based on the conserved and functional middle region of nucleocapsid protein to detect distemper infection in dogs.

    PubMed

    Latha, D; Geetha, M; Ramadass, P; Narayanan, R B

    2007-03-10

    A 287bp fragment from the middle region of the nucleocapsid protein of canine distemper virus (CDV) was amplified from the conjunctival samples of distemper-infected dogs and was cloned into pRSET B vector. The recombinant protein was expressed as a 16-kDa-fusion protein with histidine tag in E. coli. Sera of distemper-infected and vaccinated dogs contained IgG antibodies against the purified recombinant protein as observed by enzyme linked immunosorbent assays (ELISA) and showed a strong correlation (r=0.882, p<0.0001 at 95% CI) and good agreement (kappa=0.718) with the conventional tissue culture viral antigen based ELISA. Further, the results of recombinant protein based ELISA and Western blotting with the sera from the infected and vaccinated dogs correlated well (kappa=0.8226). These findings recommend the use of the recombinant protein in the serodiagnosis of canine distemper virus infection in dogs.

  17. Absence of measles virus and canine distemper virus transcripts in long-term bone marrow cultures from patients with Paget's disease of bone.

    PubMed

    Ooi, C G; Walsh, C A; Gallagher, J A; Fraser, W D

    2000-09-01

    The presence of intranuclear inclusions in pagetic osteoclasts with similar characteristics to those seen in some slow viral diseases has lead to the hypothesis that Paget's disease is caused by a similar infection. Bone marrow aspirates from seven patients with hemipelvic Paget's disease were taken from both sides of the pelvis and cultured under identical conditions. RNA was extracted after approximately 2 weeks of culture and reverse transcriptase-linked polymerase chain reaction used to investigate the expression of measles and canine distemper virus RNA. We were unable to detect the presence of measles virus (MV) or canine distemper virus (CDV) transcripts in bone marrow cultures from either affected or unaffected sites in any of our patients. The results of this study do not support a role for MV or CDV in the pathogenesis of Paget's disease of bone.

  18. The V domain of dog PVRL4 (nectin-4) mediates canine distemper virus entry and virus cell-to-cell spread

    SciTech Connect

    Delpeut, Sebastien; Noyce, Ryan S.; Richardson, Christopher D.

    2014-04-15

    The entry of canine distemper virus (CDV) is a multistep process that involves the attachment of CDV hemagglutinin (H) to its cellular receptor, followed by fusion between virus and cell membranes. Our laboratory recently identified PVRL4 (nectin-4) to be the epithelial receptor for measles and canine distemper viruses. In this study, we demonstrate that the V domain of PVRL4 is critical for CDV entry and virus cell-to-cell spread. Furthermore, four key amino acid residues within the V domain of dog PVRL4 and two within the CDV hemagglutinin were shown to be essential for receptor-mediated virus entry. - Highlights: • PVRL4 (nectin-4) is the epithelial cell receptor for measles and canine distemper viruses. • V domain of PVRL4 is critical for CDV entry, cell-to-cell spread, and syncytia formation. • Chimeric PVRL1 backbone substituted with the V domain of PVRL4 can function as a receptor. • Amino acids (F132/P133/A134/G135) within the V domain are essential for PVRL4 receptor activity. • Amino acids (P493/Y539) within CDV H protein are essential for PVRL4 receptor interaction.

  19. Emergence of canine distemper virus strains with modified molecular signature and enhanced neuronal tropism leading to high mortality in wild carnivores.

    PubMed

    Origgi, F C; Plattet, P; Sattler, U; Robert, N; Casaubon, J; Mavrot, F; Pewsner, M; Wu, N; Giovannini, S; Oevermann, A; Stoffel, M H; Gaschen, V; Segner, H; Ryser-Degiorgis, M-P

    2012-11-01

    An ongoing canine distemper epidemic was first detected in Switzerland in the spring of 2009. Compared to previous local canine distemper outbreaks, it was characterized by unusually high morbidity and mortality, rapid spread over the country, and susceptibility of several wild carnivore species. Here, the authors describe the associated pathologic changes and phylogenetic and biological features of a multiple highly virulent canine distemper virus (CDV) strain detected in and/or isolated from red foxes (Vulpes vulpes), Eurasian badgers (Meles meles), stone (Martes foina) and pine (Martes martes) martens, from a Eurasian lynx (Lynx lynx), and a domestic dog. The main lesions included interstitial to bronchointerstitial pneumonia and meningopolioencephalitis, whereas demyelination--the classic presentation of CDV infection--was observed in few cases only. In the brain lesions, viral inclusions were mainly in the nuclei of the neurons. Some significant differences in brain and lung lesions were observed between foxes and mustelids. Swiss CDV isolates shared together with a Hungarian CDV strain detected in 2004. In vitro analysis of the hemagglutinin protein from one of the Swiss CDV strains revealed functional and structural differences from that of the reference strain A75/17, with the Swiss strain showing increased surface expression and binding efficiency to the signaling lymphocyte activation molecule (SLAM). These features might be part of a novel molecular signature, which might have contributed to an increase in virus pathogenicity, partially explaining the high morbidity and mortality, the rapid spread, and the large host spectrum observed in this outbreak.

  20. In vitro inhibition of canine distemper virus by flavonoids and phenolic acids: implications of structural differences for antiviral design.

    PubMed

    Carvalho, O V; Botelho, C V; Ferreira, C G T; Ferreira, H C C; Santos, M R; Diaz, M A N; Oliveira, T T; Soares-Martins, J A P; Almeida, M R; Silva, A

    2013-10-01

    Infection caused by canine distemper virus (CDV) is a highly contagious disease with high incidence and lethality in the canine population. Antiviral activity of flavonoids quercetin, morin, rutin and hesperidin, and phenolic cinnamic, trans-cinnamic and ferulic acids were evaluated in vitro against the CDV using the time of addition assay to determine which step of the viral replicative cycle was affected. All flavonoids displayed great viral inhibition when they were added at the times 0 (adsorption) and 1h (penetration) of the viral replicative cycle. Both quercetin and hesperidin presented antiviral activity at the time 2h (intracellular). In the other hand, cinnamic acid showed antiviral activity at the times 0 and 2h while trans-cinnamic acid showed antiviral effect at the times -1h (pre-treatment) and 0 h. Ferulic acid inhibited CDV replicative cycle at the times 0 and 1h. Our study revealed promising candidates to be considered in the treatment of CDV. Structural differences among compounds and correlation to their antiviral activity were also explored. Our analysis suggest that these compounds could be useful in order to design new antiviral drugs against CDV as well as other viruses of great meaning in veterinary medicine.

  1. Influence of persistent canine distemper virus infection on expression of RECK, matrix-metalloproteinases and their inhibitors in a canine macrophage/monocytic tumour cell line (DH82).

    PubMed

    Puff, Christina; Krudewig, Christiane; Imbschweiler, Ilka; Baumgärtner, Wolfgang; Alldinger, Susanne

    2009-10-01

    A morbillivirus infection of tumour cells is known to exert oncolytic activity, but the mechanism of this inhibitory action has not been well defined. Matrix metalloproteinases (MMPs) are important enzymes degrading the extracellular matrix and are often upregulated in malignant neoplasms. Recent studies have demonstrated that RECK may potently suppress MMP-2 and -9 activity, thus inhibiting angiogenesis and metastasis. In this study, real time quantitative polymerase chain reaction (RT-qPCR) was used to determine the effect of persistent infection with canine distemper virus (CDV) infection on the expression of MMPs and their inhibitors (TIMPS) in a canine macrophage/monocytic tumour cell line (DH82). The activity of proMMP-2 and proMMP-9 was also verified zymographically. Following CDV infection, MMP-2, TIMP-1 and TIMP-2 were down-regulated, while RECK was upregulated. These findings suggest that CDV infection restores RECK expression in tumour cells and may interfere with the intracellular processing of MMPs and TIMPs, thus possibly influencing tumour cell behaviour beneficially for the host. However, this needs to be verified in in vivo studies.

  2. Epidemiology of canine distemper and canine parvovirus in domestic dogs in urban and rural areas of the Araucanía region in Chile.

    PubMed

    Acosta-Jamett, G; Surot, D; Cortés, M; Marambio, V; Valenzuela, C; Vallverdu, A; Ward, M P

    2015-08-05

    To assess whether the seroprevalence of canine distemper virus (CDV) and canine parvovirus (CPV) in domestic dogs is higher in urban versus rural areas of the Araucanía region in Chile and risk factors for exposure, a serosurvey and questionnaire survey at three, urban-rural paired sites was conducted from 2009 to 2012. Overall, 1161 households were interviewed of which 71% were located in urban areas. A total of 501 blood samples were analysed. The overall CDV and CPV seroprevalences were 61% (CI 90%: 58-70%) and 47% (CI 90%: 40-49%), and 89% (CI 90%: 85-92%) and 72% (CI 90%: 68-76%) in urban and rural areas, respectively. The higher seroprevalence in domestic dogs in urban areas suggests that urban domestic dogs might be a maintenance host for both CDV and CPV in this region. Due to the presence of endangered wild canids populations in areas close to these domestic populations, surveillance and control of these pathogens in urban dog populations is needed a priority.

  3. Variable transcription of pro- and anti-inflammatory cytokines in phocine lymphocytes following canine distemper virus infection.

    PubMed

    Seibel, H; Siebert, U; Rosenberger, T; Baumgärtner, W

    2014-10-15

    Canine distemper virus (CDV) is a highly contagious viral pathogen. Domesticated dogs are the main reservoir of CDV. Although phocine distemper virus was responsible for the recent epidemics in seals in the North and Baltic Seas, most devastating epidemics in seals were also caused by CDV. To further study the pathogenesis of CDV infection in seals, it was the aim of the present study to investigate the mechanisms of CDV induced immunosuppression in seals by analyzing the gene transcription of different pro- and anti-inflammatory cytokines in Concanavalin A (Con A) stimulated and non-stimulated phocine lymphocytes in vitro following infection with the CDV Onderstepoort (CDV-OND) strain. Phocine lymphocytes were isolated via density gradient centrifugation. The addition of 1 μg/ml Con A and virus was either performed simultaneously or lymphocytes were stimulated for 48 h with Con A prior to virus infection. Gene transcription of interleukin (IL)-6, IL-12 and tumor necrosis factor alpha (TNFα) as pro-inflammatory cytokines and IL-4, IL-10 and transforming growth factor beta (TGFβ) as anti-inflammatory cytokines were determined by using RT-qPCR. CDV-OND infection caused an initial increase of pro-inflammatory phocine cytokines mRNA 24h after infection, followed by a decrease in gene transcription after 48 h. A strong increase in the transcription of IL-4 and TGFβ was detected after 48 h when virus and mitogen were added simultaneously. An increased IL-10 production occurred only when stimulation and infection were performed simultaneously. Furthermore, an inhibition of IL-12 on IL-4 was noticed in phocine lymphocytes which were stimulated for 48 h prior to infection. In summary, the duration of the stimulation or the lymphocytes seem to have an important influence on the cytokine transcription and indicates that the outcome of CDV infection is dependent on various factors that might sensitize lymphocytes or make them more susceptible or reactive to CDV infection.

  4. Recombinant vaccine for canine parvovirus in dogs.

    PubMed Central

    López de Turiso, J A; Cortés, E; Martínez, C; Ruiz de Ybáñez, R; Simarro, I; Vela, C; Casal, I

    1992-01-01

    VP2 is the major component of canine parvovirus (CPV) capsids. The VP2-coding gene was engineered to be expressed by a recombinant baculovirus under the control of the polyhedrin promoter. A transfer vector that contains the lacZ gene under the control of the p10 promoter was used in order to facilitate the selection of recombinants. The expressed VP2 was found to be structurally and immunologically indistinguishable from authentic VP2. The recombinant VP2 shows also the capability to self-assemble, forming viruslike particles similar in size and appearance to CPV virions. These viruslike particles have been used to immunize dogs in different doses and combinations of adjuvants, and the anti-CPV responses have been measured by enzyme-linked immunosorbent assay, monolayer protection assays, and an assay for the inhibition of hemagglutination. A dose of ca. 10 micrograms of VP2 was able to elicit a good protective response, higher than that obtained with a commercially available, inactivated vaccine. The results indicate that these viruslike particles can be used to protect dogs from CPV infection. Images PMID:1313899

  5. Identification of a novel canine distemper virus B-cell epitope using a monoclonal antibody against nucleocapsid protein.

    PubMed

    Yi, Li; Cheng, Yuening; Zhang, Miao; Cao, Zhigang; Tong, Mingwei; Wang, Jianke; Zhao, Hang; Lin, Peng; Cheng, Shipeng

    2016-02-02

    Canine distemper virus (CDV) is a member of the genus Morbillivirus within the family Paramyxoviridae and has caused severe economic losses in China. Nucleocapsid protein (N) is the major structural viral protein and can be used to diagnose CDV and other morbilliviruses. In this study, a specific monoclonal antibody, 1N8, was produced against the CDV N protein (amino acids 277-471). A linear N protein epitope was identified by subjecting a series of partially overlapping synthesized peptides to enzyme-linked immunosorbent assay (ELISA) analysis. The results indicated that (350)LNFGRSYFDPA(360) was the minimal linear epitope that could be recognized by mAb 1N8. ELISA assays revealed that mouse anti-CDV sera could also recognize the minimal linear epitope. Alignment analysis of the amino acid sequences indicated that the epitope was highly conserved among CDV strains. Furthermore, the epitope was conserved among other morbilliviruses, which was confirmed with PRRV using western blotting. Taken together, the results of this study may have potential applications in the development of suitable diagnostic techniques for CDV or other morbilliviruses.

  6. Dog nectin-4 is an epithelial cell receptor for canine distemper virus that facilitates virus entry and syncytia formation.

    PubMed

    Noyce, Ryan S; Delpeut, Sebastien; Richardson, Christopher D

    2013-02-05

    Canine distemper virus (CDV) was shown to use dog nectin-4 as a receptor to gain entry into epithelial cells. RNA from dog placenta or MDCK kidney cells was isolated and cDNAs were prepared. Two splice variants of dog nectin-4 were identified. A deletion of 25 amino acids was found in the cytoplasmic domain of dog nectin-4 from MDCK cells, corresponding to a splice variant that is also seen in murine nectin-4, and did not affect its role as a receptor. Both dog nectin-4 and human nectin-4 could function as an entry factor for CDV containing an EGFP reporter gene. Inhibition of dog nectin-4 expression by RNAi or nectin-4 antibodies decreased CDV titers and EGFP fluorescence. Finally, dog nectin-4 also promotes syncytia formation, which could be inhibited by siRNA treatment. These data confirm that dog nectin-4 can be used by CDV to gain entry into epithelial cells, and facilitate virus spread.

  7. Region between the canine distemper virus M and F genes modulates virulence by controlling fusion protein expression.

    PubMed

    Anderson, Danielle E; von Messling, Veronika

    2008-11-01

    Morbilliviruses, including measles and canine distemper virus (CDV), are nonsegmented, negative-stranded RNA viruses that cause severe diseases in humans and animals. The transcriptional units in their genomes are separated by untranslated regions (UTRs), which contain essential transcription and translation signals. Due to its increased length, the region between the matrix (M) protein and fusion (F) protein open reading frames is of particular interest. In measles virus, the entire F 5' region is untranslated, while several start codons are found in most other morbilliviruses, resulting in a long F protein signal peptide (Fsp). To characterize the role of this region in morbillivirus pathogenesis, we constructed recombinant CDVs, in which either the M-F UTR was replaced with that between the nucleocapsid (N) and phosphoprotein (P) genes, or 106 Fsp residues were deleted. The Fsp deletion alone had no effect in vitro and in vivo. In contrast, substitution of the UTR was associated with a slight increase in F gene and protein expression. Animals infected with this virus either recovered completely or experienced prolonged disease and death due to neuroinvasion. The combination of both changes resulted in a virus with strongly increased F gene and protein expression and complete attenuation. Taken together, our results provide evidence that the region between the morbillivirus M and F genes modulates virulence through transcriptional control of the F gene expression.

  8. Lymphotropism and host responses during acute wild-type canine distemper virus infections in a highly susceptible natural host.

    PubMed

    Nielsen, Line; Søgaard, Mette; Jensen, Trine Hammer; Andersen, Mads Klindt; Aasted, Bent; Blixenkrone-Møller, Merete

    2009-09-01

    The mechanisms behind the in vivo virulence of immunosuppressive wild-type morbillivirus infections are still not fully understood. To investigate lymphotropism and host responses, we have selected the natural host model of canine distemper virus (CDV) infection in mink. This model displays multisystemic infection, similar to measles virus and rinderpest virus infections in their susceptible natural hosts. The wild-type CDVs investigated provoked marked virulence differences, inducing mild versus marked to severe acute disease. The mildly virulent wild-type virus induced transient lymphopenia, despite the development of massive infection of peripheral blood mononuclear cells (PBMCs) exceeding that determined for the highly virulent wild-type virus, indicating an inverse relationship between acute virulence and the extent of viraemia in the investigated wild-type viruses. Single-cell cytokine production in PBMCs was investigated throughout the acute infections. We observed Th1- and Th2-type cytokine responses beginning in the prodromal phase, and late inflammatory responses were shared between the wild-type infections.

  9. Comparison of molecular and growth properties for two different canine distemper virus clusters, Asia 1 and 2, in Japan.

    PubMed

    Lan, Nguyen Thi; Yamaguchi, Ryoji; Kawabata, Atsushi; Uchida, Kazuyuki; Sugano, Sumio; Tateyama, Susumu

    2007-07-01

    To compare the molecular and growth properties of two newly isolated canine distemper virus strains in the Asia 1 and 2 groups with clinico-pathological findings in dogs, nucleotide and predicted amino acid sequence comparisons of genes H and P were performed together with comparative growth profiling. The predicted amino acid sequences of the H gene contained 12 cysteine residues that were conserved among the examined Asia 1 and Asia 2 viruses. The hydrophobic region in the H gene of the Asia 2 isolates was one amino acid longer than that of the Asia 1 group. The H gene of the Asia 1 group had nine putative asparagine (N)-linked glycosylation sites, while there were eight sites in the Asia 2 group. The titers of the cell-associated viruses for the Asia 1 strains were higher than those of the released viruses and were opposite to those of the Asia 2 strains in a previous study. The molecular and growth properties of the Asia 1 and Asia 2 groups seem to vary, although no significant differences were observed in the clinical signs and pathological findings between the two groups.

  10. Synergistic inhibition in cell-cell fusion mediated by the matrix and nucleocapsid protein of canine distemper virus.

    PubMed

    Wiener, Dominique; Plattet, Philippe; Cherpillod, Pascal; Zipperle, Ljerka; Doherr, Marcus G; Vandevelde, Marc; Zurbriggen, Andreas

    2007-11-01

    Canine distemper virus (CDV) causes a chronic, demyelinating, progressive or relapsing neurological disease in dogs, because CDV persists in the CNS. Persistence of virulent CDV, such as the A75/17 strain has been reproduced in cell cultures where it is associated with a non-cytolytic infection with very limited cell-cell fusion. This is in sharp contrast to attenuated CDV infection in cell cultures, such as the Onderstepoort (OP) CDV strain, which produces extensive fusion activity and cytolysis. Fusion efficiency may be determined by the structure of the viral fusion protein per se but also by its interaction with other structural proteins of CDV. This was studied by combining genes derived from persistent and non-persistent CDV strains in transient transfection experiments. It was found that fusion efficiency was markedly attenuated by the structure of the fusion protein of the neurovirulent A75/17-CDV. Moreover, we showed that the interaction of the surface glycoproteins with the M protein of the persistent strain greatly influenced fusion activity. Site directed mutagenesis showed that the c-terminus of the M protein is of particular importance in this respect. Interestingly, although the nucleocapsid protein alone did not affect F/H-induced cell-cell fusion, maximal inhibition occurred when the latter was added to combined glycoproteins with matrix protein. Thus, the present study suggests that very limited fusogenicity in virulent CDV infection, which favours persistence by limiting cell destruction involves complex interactions between all viral structural proteins.

  11. Wildlife reservoirs of canine distemper virus resulted in a major outbreak in Danish farmed mink (Neovison vison).

    PubMed

    Trebbien, Ramona; Chriel, Mariann; Struve, Tina; Hjulsager, Charlotte Kristiane; Larsen, Gitte; Larsen, Lars Erik

    2014-01-01

    A major outbreak of canine distemper virus (CDV) in Danish farmed mink (Neovison vison) started in the late summer period of 2012. At the same time, a high number of diseased and dead wildlife species such as foxes, raccoon dogs, and ferrets were observed. To track the origin of the outbreak virus full-length sequencing of the receptor binding surface protein hemagglutinin (H) was performed on 26 CDV's collected from mink and 10 CDV's collected from wildlife species. Subsequent phylogenetic analyses showed that the virus circulating in the mink farms and wildlife were highly identical with an identity at the nucleotide level of 99.45% to 100%. The sequences could be grouped by single nucleotide polymorphisms according to geographical distribution of mink farms and wildlife. The signaling lymphocytic activation molecule (SLAM) receptor binding region in most viruses from both mink and wildlife contained G at position 530 and Y at position 549; however, three mink viruses had an Y549H substitution. The outbreak viruses clustered phylogenetically in the European lineage and were highly identical to wildlife viruses from Germany and Hungary (99.29% - 99.62%). The study furthermore revealed that fleas (Ceratophyllus sciurorum) contained CDV and that vertical transmission of CDV occurred in a wild ferret. The study provides evidence that wildlife species, such as foxes, play an important role in the transmission of CDV to farmed mink and that the virus may be maintained in the wild animal reservoir between outbreaks.

  12. Arctic lineage-canine distemper virus as a cause of death in Apennine wolves (Canis lupus) in Italy.

    PubMed

    Di Sabatino, Daria; Lorusso, Alessio; Di Francesco, Cristina E; Gentile, Leonardo; Di Pirro, Vincenza; Bellacicco, Anna Lucia; Giovannini, Armando; Di Francesco, Gabriella; Marruchella, Giuseppe; Marsilio, Fulvio; Savini, Giovanni

    2014-01-01

    Canine distemper virus (CDV) infection is a primary threat affecting a wide number of carnivore species, including wild animals. In January 2013, two carcasses of Apennine wolves (Canis lupus) were collected in Ortona dei Marsi (L'Aquila province, Italy) by the local Veterinary Services. CDV was immediately identified either by RT-PCR or immunohistochemistry in lung and central nervous tissue samples. At the same time, severe clinical signs consistent with CDV infection were identified and taped (Videos S1-S3) from three wolves rescued in the areas surrounding the National Parks of the Abruzzi region by the Veterinary Services. The samples collected from these symptomatic animals also turned out CDV positive by RT-PCR. So far, 30 carcasses of wolves were screened and CDV was detected in 20 of them. The sequencing of the haemagglutinin gene and subsequent phylogenetic analysis demonstrated that the identified virus belonged to the CDV Arctic lineage. Strains belonging to this lineage are known to circulate in Italy and in Eastern Europe amongst domestic dogs. To the best of our knowledge this is the first report of CDV Arctic lineage epidemics in the wild population in Europe.

  13. Fatal combined infection with canine distemper virus and orthopoxvirus in a group of Asian marmots (Marmota caudata).

    PubMed

    Origgi, F C; Sattler, U; Pilo, P; Waldvogel, A S

    2013-09-01

    A fatal combined infection with canine distemper virus (CDV) and orthopoxvirus (OPXV) in Asian marmots (Marmota caudata) is reported in this article. A total of 7 Asian marmots from a small zoological garden in Switzerland were found dead in hibernation during a routine check in the winter of 2011. The marmots died in February 2011. No clinical signs of disease were observed at any time. The viruses were detected in all individuals for which the tissues were available (n = 3). Detection of the viruses was performed by reverse transcription polymerase chain reaction. The most consistent gross lesion was a neck and thorax edema. A necrotizing pharyngitis and a multifocal necrotizing pneumonia were observed histologically. Numerous large intracytoplasmic eosinophilic inclusions were seen in the epithelial cells of the pharynx, of the airways, and in the skin keratinocytes. Brain lesions were limited to mild multifocal gliosis. Phylogenetic analysis revealed that the marmot CDV strain was closely related to the clusters of CDVs detected in Switzerland in wild carnivores during a local outbreak in 2002 and the 2009-2010 nationwide epidemic, suggesting a spillover of this virus from wildlife. The OPXV was most closely related to a strain of cowpoxvirus, a poxvirus species considered endemic in Europe. This is the first reported instance of CDV infection in a rodent species and of a combined CDV and OPXV infection.

  14. Pathogenesis and phylogenetic analyses of canine distemper virus strain ZJ7 isolate from domestic dogs in China.

    PubMed

    Tan, Bin; Wen, Yong-Jun; Wang, Feng-Xue; Zhang, Shu-Qin; Wang, Xiu-Dong; Hu, Jia-Xin; Shi, Xin-Chuan; Yang, Bo-Chao; Chen, Li-Zhi; Cheng, Shi-Peng; Wu, Hua

    2011-11-16

    A new isolate of canine distemper virus (CDV), named ZJ7, was isolated from lung tissues of a dog suspected with CDV infection using MDCK cells. The ZJ7 isolate induced cytopathogenic effects of syncytia in MDCK cell after six passages. In order to evaluate pathogenesis of ZJ7 strain, three CDV sero-negative dogs were intranasally inoculated with its virus suspension. All infected dogs developed clinical signs of severe bloody diarrhea, conjunctivitis, ocular discharge, nasal discharge and coughing, fever and weight loss at 21 dpi, whereas the mock group infected with DMEM were normal. The results demonstrated that CDV-ZJ7 strain isolated by MDCK cell was virulent, and the nucleotide and amino acid sequences of strain ZJ7 had no change after isolation by MDCK cell when compared with the original virus from the fresh tissues. Molecular and phylogenetic analyses for the nucleocapsid (N), phosphoprotein (P) and receptor binding haemagglutinin (H) gene of the ZJ7 isolate clearly showed it is joins to the Asia 1 group cluster of CDV strains, the predominant genotype in China.

  15. Impacts of canine distemper virus infection on the giant panda population from the perspective of gut microbiota

    PubMed Central

    Zhao, Na; Li, Meng; Luo, Jing; Wang, Supen; Liu, Shelan; Wang, Shan; Lyu, Wenting; Chen, Lin; Su, Wen; Ding, Hua; He, Hongxuan

    2017-01-01

    The recent increase in infectious disease outbreaks has been directly linked to the global loss of biodiversity and the decline of some endangered species populations. Between December 2014 and March 2015, five captive giant pandas died due to canine distemper virus (CDV) infection in China. CDV has taken a heavy toll on tigers and lions in recent years. Here, we describe the first gut microbiome diversity study of CDV-infected pandas. By investigating the influence of CDV infection on gut bacterial communities in infected and uninfected individuals and throughout the course of infection, we found that CDV infection distorted the gut microbiota composition by reducing the prevalence of the dominant genera, Escherichia and Clostridium, and increasing microbial diversity. Our results highlight that increases in intestinal inflammation and changes in the relative abundances of pathogen-containing gut communities occur when individuals become infected with CDV. These results may provide new insights into therapeutics that target the microbiota to attenuate the progression of CDV disease and to reduce the risk of gut-linked disease in individuals with CDV. In addition, our findings underscore the need for better information concerning the dynamics of infection and the damage caused by pathogens in panda populations. PMID:28051146

  16. Impacts of canine distemper virus infection on the giant panda population from the perspective of gut microbiota.

    PubMed

    Zhao, Na; Li, Meng; Luo, Jing; Wang, Supen; Liu, Shelan; Wang, Shan; Lyu, Wenting; Chen, Lin; Su, Wen; Ding, Hua; He, Hongxuan

    2017-01-04

    The recent increase in infectious disease outbreaks has been directly linked to the global loss of biodiversity and the decline of some endangered species populations. Between December 2014 and March 2015, five captive giant pandas died due to canine distemper virus (CDV) infection in China. CDV has taken a heavy toll on tigers and lions in recent years. Here, we describe the first gut microbiome diversity study of CDV-infected pandas. By investigating the influence of CDV infection on gut bacterial communities in infected and uninfected individuals and throughout the course of infection, we found that CDV infection distorted the gut microbiota composition by reducing the prevalence of the dominant genera, Escherichia and Clostridium, and increasing microbial diversity. Our results highlight that increases in intestinal inflammation and changes in the relative abundances of pathogen-containing gut communities occur when individuals become infected with CDV. These results may provide new insights into therapeutics that target the microbiota to attenuate the progression of CDV disease and to reduce the risk of gut-linked disease in individuals with CDV. In addition, our findings underscore the need for better information concerning the dynamics of infection and the damage caused by pathogens in panda populations.

  17. Serosurvey for canine distemper virus, canine adenovirus, Leptospira interrogans, and Toxoplasma gondii in free-ranging canids in Scandinavia and Svalbard.

    PubMed

    Akerstedt, Johan; Lillehaug, Atle; Larsen, Inger-Lise; Eide, Nina E; Arnemo, Jon M; Handeland, Kjell

    2010-04-01

    Prevalence of antibodies reactive to canine distemper virus (CDV), canine adenovirus type 1 (CAV-1), Leptospira interrogans serovars Canicola and Icterohaemorrhagiae, and Toxoplasma gondii were examined in free-ranging Scandinavian canids. Sampling included 275 red foxes (Vulpes vulpes) from mainland Norway, 60 arctic foxes (Vulpes lagopus) from the high-arctic islands of Svalbard, and 98 wolves (Canis lupus) from the joint Swedish-Norwegian population. Methods used included virus neutralization tests for CDV and CAV-1, a microscopic agglutination test for L. interrogans, and a direct agglutination test for T. gondii. High prevalence of antibody to CAV-1 was identified in red foxes (59.6%), wolves (67.7%), and arctic foxes (37.8%). The prevalence of antibody to CDV varied between 9.6% and 12.3% in the three species. Antibodies to L. interrogans serovar Icterohaemorrhagiae were found in 9.9% of the red foxes and 8.4% of the wolves sampled, whereas no antibody-positive arctic foxes were found. All animals were antibody-negative for L. interrogans serovar Canicola. Antibodies to T. gondii were found in 66.9, 51.7, and 18.6% of red foxes, arctic foxes and wolves, respectively. Significantly more adults than juveniles were antibody-positive for CDV in red foxes and arctic foxes, for CAV-1 in wolves, and for T. gondii in red foxes and wolves. There was a general tendency for adult female red foxes to have a higher prevalence of antibodies for CDV than adult males; this difference was statistically significant. The results indicate that CDV and CAV-1 are endemic in red foxes and wolves on the Scandinavian mainland and in arctic foxes on Svalbard. Although infection with L. interrogans serovar Icterohaemorrhagiae was relatively common in wild canids on mainland Norway, it was not found on Svalbard, where the maintenance host (Rattus norvegicus) is absent. All three species are commonly exposed to T. gondii through predation on infected intermediate hosts.

  18. Development of a duplex real-time RT-qPCR assay to monitor genome replication, gene expression and gene insert stability during in vivo replication of a prototype live attenuated canine distemper virus vector encoding SIV gag.

    PubMed

    Coleman, John W; Wright, Kevin J; Wallace, Olivia L; Sharma, Palka; Arendt, Heather; Martinez, Jennifer; DeStefano, Joanne; Zamb, Timothy P; Zhang, Xinsheng; Parks, Christopher L

    2015-03-01

    Advancement of new vaccines based on live viral vectors requires sensitive assays to analyze in vivo replication, gene expression and genetic stability. In this study, attenuated canine distemper virus (CDV) was used as a vaccine delivery vector and duplex 2-step quantitative real-time RT-PCR (RT-qPCR) assays specific for genomic RNA (gRNA) or mRNA have been developed that concurrently quantify coding sequences for the CDV nucleocapsid protein (N) and a foreign vaccine antigen (SIV Gag). These amplicons, which had detection limits of about 10 copies per PCR reaction, were used to show that abdominal cavity lymphoid tissues were a primary site of CDV vector replication in infected ferrets, and importantly, CDV gRNA or mRNA was undetectable in brain tissue. In addition, the gRNA duplex assay was adapted for monitoring foreign gene insert genetic stability during in vivo replication by analyzing the ratio of CDV N and SIV gag genomic RNA copies over the course of vector infection. This measurement was found to be a sensitive probe for assessing the in vivo genetic stability of the foreign gene insert.

  19. Immunological responses to polyvalent canine vaccines in dogs.

    PubMed

    Miyamoto, T; Taura, Y; Une, S; Yoshitake, M; Nakama, S; Watanabe, S

    1995-04-01

    The immunological responses to commercially available polyvalent vaccines in dogs were examined. There was a tendency in decreased lymphocyte counts on day 7 in the puppy and adult dogs. There was a significant increase in the blastogenesis of lymphocytes on day 7 and 21 in puppies, whereas no significant changes were seen in the adult dogs. Delayed type hypersensitivity (DTH) responses to phytohemagglutinin (PHA) and canine parvo-virus (CPV) vaccine monitored 0, 3, 8 weeks after vaccination produced strong reactions, in particular those to CPV vaccine rose significantly after vaccination and maintained the higher responses for at least 2 months. Therefore, it is considered that vaccination is immunomodulative rather than immunosuppressive and that DTH responses to PHA and CPV vaccine are helpful to monitor non-specific and specific immune functions in vivo.

  20. Development of a Vaccine Incorporating Killed Virus of Canine Origin for the Prevention of Canine Parvovirus Infection

    PubMed Central

    Povey, C.

    1982-01-01

    A parvovirus of canine origin, cultured in a feline kidney cell line, was inactivated with formalin. Three pilot serials were produced and three forms of finished vaccine (nonadjuvanted, single adjuvanted and double adjuvanted) were tested in vaccination and challenge trials. A comparison was also made with two inactivated feline panleukopenia virus vaccines, one of which has official approval for use in dogs. The inactivated canine vaccine in nonadjuvanted, adjuvanted or double adjuvanted form was immunogenic in 20 of 20 vaccinated dogs. The double adjuvanted vaccine is selected as the one of choice on the basis of best and most persistent seriological response. PMID:7039811

  1. Interleukin-1beta, -6, -12 and tumor necrosis factor-alpha expression in brains of dogs with canine distemper virus infection.

    PubMed

    Gröne, A; Alldinger, S; Baumgärtner, W

    2000-10-02

    Canine distemper virus infection in dogs is commonly associated with demyelinating central nervous system lesions. Investigations on viral protein expression by studying mRNA and protein distribution together with the characterization of CD4 and CD8 inflammatory cells and MHC class II up-regulation revealed a biphasic disease process. To further investigate the cellular interactions in the different plaque types the cerebella of 14 dogs with confirmed distemper infection were investigated for expression of interleukin (IL)-1beta, -6, -12 and tumor necrosis factor-alpha (TNF) by immunohistochemistry using rabbit polyclonal anti-cytokine antibodies. T-cells and astrocytes were identified with rabbit anti CD3- and GFAP-monoclonal and polyclonal antibodies, respectively; and microglia/macrophages were characterized by their ability to bind lectin from Bandeiraea simplicifolia (BS-1). To further name the cytokine expressing cells immunoenzymatic double staining using DAB and New Fuchsin was performed. White matter lesions were classified according to histopathological criteria into acute, subacute and chronic. Canine distemper virus nucleoprotein antigen was demonstrated in nearly all plaques, except in older plaques where virus was not present within the plaque but adjacent to the lesion. IL-1 expression was observed to varying degrees in all types of lesions. Most often IL-1 was present in CD3 and BS-1 positive cells in the brain parenchyma in earlier plaques and comprising perivascular cuffs found in chronic plaques. IL-6 expression was present in all lesions, and followed a similar distribution pattern as IL-1. IL-12 displayed very often a granular extracellular pattern of immunoreactivity, especially in the brain parenchyma, and was found only in individual perivascular cells. TNF staining, predominantly found in astrocytes, was present in lesions of various types; however, staining appeared to be stronger in acute lesions and decreased in chronic plaques. In the

  2. [Viruses and the neuroendocrine system: model of murine obesity induced by cerebral infection by canine distemper virus].

    PubMed

    Bernard, A; Akaoka, H; Giraudon, P; Belin, M

    1999-05-01

    It is currently well established that the nervous, endocrine and immune systems inter-communicate using biologically active soluble factors, synthesised and produced by these three systems themselves (e.g. immunomodulator effect of hormones, effect of substances secreted by immune cells on endocrine function.). In addition, these systems jointly express receptors for hormones, peptides, growth factors and cytokines. Immuno-neuroendocrine interactions therefore underlie physiological processes and their deregulation can result in various pathological states. By entering into complex relationships with the specialized and differentiated cells of these three systems viruses can alter inter-cellular communication and result in the appearance of pathological processes directly linked to these disturbances. In order to understand the role of viruses in the genesis of neuroimmunoendocrine pathologies, we have developed a cerebral infection model using canine distemper virus (CDV). In infected mice, this paramyxovirus, closely related to the human measles virus, induces early neurological pathologies (encephalitis) which are associated with active viral replication. Mice surviving the acute phase of infection exhibit motor deficits (paralysis and turning behaviour) or obesity during the viral persistence phase, despite the fact that the virus is no longer detectable. The obesity is characterised by hyperinsulinaemia, hyperleptinaemia and hyperplasia of the adipocytes, associated with decreased expression of the OB-Rb hypothalamic leptin receptor and modulated expression of hypothalamic monoamines and neuropeptides. These results support the viral "hit and run" theory, since the initial viral impact in the hypothalamus may be the origin of the changes in later immunoneuroendocrine communication. Thus, certain human neurodegenerative or neuroendocrine diseases may have a previous viral infection aetiology without it being possible to clearly identify the agent responsible.

  3. Urban domestic dog populations as a source of canine distemper virus for wild carnivores in the Coquimbo region of Chile.

    PubMed

    Acosta-Jamett, G; Chalmers, W S K; Cunningham, A A; Cleaveland, S; Handel, I G; Bronsvoort, B M deC

    2011-09-28

    Urban areas can support dog populations dense enough to maintain canine distemper virus (CDV) and can be a source of infection for rural dogs and free-ranging carnivores. The aim of this study was to investigate the relationships between urban and rural domestic dog and wild carnivore populations and their effects on the epidemiology of CDV to explain retrospectively a CD outbreak in wild foxes in 2003. From 2005 to 2007 a cross-sectional household questionnaire survey was conducted in Coquimbo and Ovalle cities, in three towns and in rural sites along two transects from these cities to the Fray Jorge National Park (FJNP) in the Coquimbo region, Chile. Blood samples were collected from unvaccinated dogs at surveyed households and from free-ranging foxes in rural areas along the transects. The seroprevalence of CDV in domestic dogs was higher in urban than in rural areas and in the later was highest in dogs born before 2001-2002. The seroprevalence of CDV in foxes was higher in areas closer to human settlements. A high seroprevalence in dogs born before 2001-2002 further supports a link between CDV patterns in rural dog and fox populations. In our study area, urban dogs are proposed to be the source of CDV infection to wild carnivores. The large dog population size and density detected in Coquimbo and Ovalle provides optimal conditions for maintaining a large and dense susceptible population of dogs, which can act as a reservoir for highly infectious diseases and could have been the source of infection in the CD outbreak in wild foxes.

  4. Two domains of the V protein of virulent canine distemper virus selectively inhibit STAT1 and STAT2 nuclear import.

    PubMed

    Röthlisberger, Anne; Wiener, Dominique; Schweizer, Matthias; Peterhans, Ernst; Zurbriggen, Andreas; Plattet, Philippe

    2010-07-01

    Canine distemper virus (CDV) causes in dogs a severe systemic infection, with a high frequency of demyelinating encephalitis. Among the six genes transcribed by CDV, the P gene encodes the polymerase cofactor protein (P) as well as two additional nonstructural proteins, C and V; of these V was shown to act as a virulence factor. We investigated the molecular mechanisms by which the P gene products of the neurovirulent CDV A75/17 strain disrupt type I interferon (IFN-alpha/beta)-induced signaling that results in the establishment of the antiviral state. Using recombinant knockout A75/17 viruses, the V protein was identified as the main antagonist of IFN-alpha/beta-mediated signaling. Importantly, immunofluorescence analysis illustrated that the inhibition of IFN-alpha/beta-mediated signaling correlated with impaired STAT1/STAT2 nuclear import, whereas the phosphorylation state of these proteins was not affected. Coimmunoprecipitation assays identified the N-terminal region of V (VNT) responsible for STAT1 targeting, which correlated with its ability to inhibit the activity of the IFN-alpha/beta-mediated antiviral state. Conversely, while the C-terminal domain of V (VCT) could not function autonomously, when fused to VNT it optimally interacted with STAT2 and subsequently efficiently suppressed the IFN-alpha/beta-mediated signaling pathway. The latter result was further supported by a single mutation at position 110 within the VNT domain of CDV V protein, resulting in a mutant that lost STAT1 binding while retaining a partial STAT2 association. Taken together, our results identified the CDV VNT and VCT as two essential modules that complement each other to interfere with the antiviral state induced by IFN-alpha/beta-mediated signaling. Hence, our experiments reveal a novel mechanism of IFN-alpha/beta evasion among the morbilliviruses.

  5. Mechanism of reduction of virus release and cell-cell fusion in persistent canine distemper virus infection.

    PubMed

    Meertens, Nadine; Stoffel, Michael H; Cherpillod, Pascal; Wittek, Riccardo; Vandevelde, Marc; Zurbriggen, Andreas

    2003-10-01

    Canine distemper virus (CDV), a mobillivirus related to measles virus causes a chronic progressive demyelinating disease, associated with persistence of the virus in the central nervous system (CNS). CNS persistence of morbilliviruses has been associated with cell-to-cell spread, thereby limiting immune detection. The mechanism of cell-to-cell spread remains uncertain. In the present study we studied viral spread comparing a cytolytic (non-persistent) and a persistent CDV strain in cell cultures. Cytolytic CDV spread in a compact concentric manner with extensive cell fusion and destruction of the monolayer. Persistent CDV exhibited a heterogeneous cell-to-cell pattern of spread without cell fusion and 100-fold reduction of infectious viral titers in supernatants as compared to the cytolytic strain. Ultrastructurally, low infectious titers correlated with limited budding of persistent CDV as compared to the cytolytic strain, which shed large numbers of viral particles. The pattern of heterogeneous cell-to-cell viral spread can be explained by low production of infectious viral particles in only few areas of the cell membrane. In this way persistent CDV only spreads to a small proportion of the cells surrounding an infected one. Our studies suggest that both cell-to-cell spread and limited production of infectious virus are related to reduced expression of fusogenic complexes in the cell membrane. Such complexes consist of a synergistic configuration of the attachment (H) and fusion (F) proteins on the cell surface. F und H proteins exhibited a marked degree of colocalization in cytolytic CDV infection but not in persistent CDV as seen by confocal laser microscopy. In addition, analysis of CDV F protein expression using vaccinia constructs of both strains revealed an additional large fraction of uncleaved fusion protein in the persistent strain. This suggests that the paucity of active fusion complexes is due to restricted intracellular processing of the viral fusion

  6. Alteration of the leptin network in late morbid obesity induced in mice by brain infection with canine distemper virus.

    PubMed

    Bernard, A; Cohen, R; Khuth, S T; Vedrine, B; Verlaeten, O; Akaoka, H; Giraudon, P; Belin, M F

    1999-09-01

    Viruses can induce progressive neurologic disorders associated with diverse pathological manifestations, and therefore, viral infection of the brain can impair differentiated neural functions, depending on the initial viral tropism. We have previously reported that canine distemper virus (CDV) targets certain mouse brain structures, including the hypothalamus, early and selectively. Infected mice exhibit acute encephalitis, with late disease, characterized by motor impairment or obesity syndrome, appearing in some of the surviving mice several months after the initial viral replication. In the present study, we show viral persistence in the hypothalami of obese mice, as demonstrated by low, but still significant, levels of CDV nucleoprotein transcripts, associated with a dramatic decrease in F gene mRNAs. Given the pivotal role of the hypothalamus in obesity (eating behavior, energy consumption, and neuroendocrine function) and that of leptin, the adipose tissue-derived satiety factor acting through hypothalamic receptors, we analyzed the leptin networks in both obese and nonobese mice. The discrepancy found between the chronic and dramatic increase in blood leptin levels and the occurrence of obesity may be due to leptin resistance in the brain. In fact, expression of the long leptin receptor isoform, representing the functional leptin receptor, was specifically downregulated in the hypothalami of obese mice, explaining their inability to generate an adequate response to leptin in the brain. Intriguingly, during the acute phase of infection, its expression was increased in CDV-targeted structures in all infected mice and remained high in obese mice in all CDV-targeted structures, except for the hypothalamus. The biphasic change in hypothalamic leptin receptor expression seen during the progression of CDV-induced obesity provides a new paradigm for understanding mechanisms of neuroendocrinological, virus-induced abnormalities.

  7. The Role of Canine Distemper Virus and Persistent Organic Pollutants in Mortality Patterns of Caspian Seals (Pusa caspica)

    PubMed Central

    Wilson, Susan C.; Eybatov, Tariel M.; Amano, Masao; Jepson, Paul D.; Goodman, Simon J.

    2014-01-01

    Persistent organic pollutants are a concern for species occupying high trophic levels since they can cause immunosuppression and impair reproduction. Mass mortalities due to canine distemper virus (CDV) occurred in Caspian seals (Pusa caspica), in spring of 1997, 2000 and 2001, but the potential role of organochlorine exposure in these epizootics remains undetermined. Here we integrate Caspian seal mortality data spanning 1971–2008, with data on age, body condition, pathology and blubber organochlorine concentration for carcases stranded between 1997 and 2002. We test the hypothesis that summed PCB and DDT concentrations contributed to CDV associated mortality during epizootics. We show that age is the primary factor explaining variation in blubber organochlorine concentrations, and that organochlorine burden, age, sex, and body condition do not account for CDV infection status (positive/negative) of animals dying in epizootics. Most animals (57%, n = 67) had PCB concentrations below proposed thresholds for toxic effects in marine mammals (17 µg/g lipid weight), and only 3 of 67 animals had predicted TEQ values exceeding levels seen to be associated with immune suppression in harbour seals (200 pg/g lipid weight). Mean organonchlorine levels were higher in CDV-negative animals indicating that organochlorines did not contribute significantly to CDV mortality in epizootics. Mortality monitoring in Azerbaijan 1971–2008 revealed bi-annual stranding peaks in late spring, following the annual moult and during autumn migrations northwards. Mortality peaks comparable to epizootic years were also recorded in the 1970s–1980s, consistent with previous undocumented CDV outbreaks. Gompertz growth curves show that Caspian seals achieve an asymptotic standard body length of 126–129 cm (n = 111). Males may continue to grow slowly throughout life. Mortality during epizootics may exceed the potential biological removal level (PBR) for the population, but the low

  8. Estimating the potential impact of canine distemper virus on the Amur tiger population (Panthera tigris altaica) in Russia.

    PubMed

    Gilbert, Martin; Miquelle, Dale G; Goodrich, John M; Reeve, Richard; Cleaveland, Sarah; Matthews, Louise; Joly, Damien O

    2014-01-01

    Lethal infections with canine distemper virus (CDV) have recently been diagnosed in Amur tigers (Panthera tigris altaica), but long-term implications for the population are unknown. This study evaluates the potential impact of CDV on a key tiger population in Sikhote-Alin Biosphere Zapovednik (SABZ), and assesses how CDV might influence the extinction potential of other tiger populations of varying sizes. An individual-based stochastic, SIRD (susceptible-infected-recovered/dead) model was used to simulate infection through predation of infected domestic dogs, and/or wild carnivores, and direct tiger-to-tiger transmission. CDV prevalence and effective contact based on published and observed data was used to define plausible low- and high-risk infection scenarios. CDV infection increased the 50-year extinction probability of tigers in SABZ by 6.3% to 55.8% compared to a control population, depending on risk scenario. The most significant factors influencing model outcome were virus prevalence in the reservoir population(s) and its effective contact rate with tigers. Adjustment of the mortality rate had a proportional impact, while inclusion of epizootic infection waves had negligible additional impact. Small populations were found to be disproportionately vulnerable to extinction through CDV infection. The 50-year extinction risk in populations consisting of 25 individuals was 1.65 times greater when CDV was present than that of control populations. The effects of density dependence do not protect an endangered population from the impacts of a multi-host pathogen, such as CDV, where they coexist with an abundant reservoir presenting a persistent threat. Awareness of CDV is a critical component of a successful tiger conservation management policy.

  9. The role of canine distemper virus and persistent organic pollutants in mortality patterns of Caspian seals (Pusa caspica).

    PubMed

    Wilson, Susan C; Eybatov, Tariel M; Amano, Masao; Jepson, Paul D; Goodman, Simon J

    2014-01-01

    Persistent organic pollutants are a concern for species occupying high trophic levels since they can cause immunosuppression and impair reproduction. Mass mortalities due to canine distemper virus (CDV) occurred in Caspian seals (Pusa caspica), in spring of 1997, 2000 and 2001, but the potential role of organochlorine exposure in these epizootics remains undetermined. Here we integrate Caspian seal mortality data spanning 1971-2008, with data on age, body condition, pathology and blubber organochlorine concentration for carcases stranded between 1997 and 2002. We test the hypothesis that summed PCB and DDT concentrations contributed to CDV associated mortality during epizootics. We show that age is the primary factor explaining variation in blubber organochlorine concentrations, and that organochlorine burden, age, sex, and body condition do not account for CDV infection status (positive/negative) of animals dying in epizootics. Most animals (57%, n = 67) had PCB concentrations below proposed thresholds for toxic effects in marine mammals (17 µg/g lipid weight), and only 3 of 67 animals had predicted TEQ values exceeding levels seen to be associated with immune suppression in harbour seals (200 pg/g lipid weight). Mean organonchlorine levels were higher in CDV-negative animals indicating that organochlorines did not contribute significantly to CDV mortality in epizootics. Mortality monitoring in Azerbaijan 1971-2008 revealed bi-annual stranding peaks in late spring, following the annual moult and during autumn migrations northwards. Mortality peaks comparable to epizootic years were also recorded in the 1970s-1980s, consistent with previous undocumented CDV outbreaks. Gompertz growth curves show that Caspian seals achieve an asymptotic standard body length of 126-129 cm (n = 111). Males may continue to grow slowly throughout life. Mortality during epizootics may exceed the potential biological removal level (PBR) for the population, but the low frequency of

  10. Recent host range expansion of canine distemper virus and variation in its receptor, the signaling lymphocyte activation molecule, in carnivores.

    PubMed

    Ohishi, Kazue; Suzuki, Rintaro; Maeda, Taro; Tsuda, Miwako; Abe, Erika; Yoshida, Takao; Endo, Yasuyuki; Okamura, Maki; Nagamine, Takashi; Yamamoto, Hanae; Ueda, Miya; Maruyama, Tadashi

    2014-07-01

    The signaling lymphocyte activation molecule (SLAM) is a receptor for morbilliviruses. To understand the recent host range expansion of canine distemper virus (CDV) in carnivores, we determined the nucleotide sequences of SLAMs of various carnivores and generated three-dimensional homology SLAM models. Thirty-four amino acid residues were found for the candidates binding to CDV on the interface of the carnivore SLAMs. SLAM of the domestic dog (Canis lupus familiaris) were similar to those of other members of the suborder Caniformia, indicating that the animals in this group have similar sensitivity to dog CDV. However, they were different at nine positions from those of felids. Among the nine residues, four of domestic cat (Felis catus) SLAM (72, 76, 82, and 129) and three of lion (Panthera leo persica) SLAM (72, 82, and 129) were associated with charge alterations, suggesting that the felid interfaces have lower affinities to dog CDV. Only the residue at 76 was different between domestic cat and lion SLAM interfaces. The domestic cat SLAM had threonine at 76, whereas the lion SLAM had arginine, a positively charged residue like that of the dog SLAM. The cat SLAM with threonine is likely to have lower affinity to CDV-H and to confer higher resistance against dog CDV. Thus, the four residues (72, 76, 82, and 129) on carnivore SLAMs are important for the determination of affinity and sensitivity with CDV. Additionally, the CDV-H protein of felid strains had a substitution of histidine for tyrosine at 549 of dog CDV-H and may have higher affinity to lion SLAM. Three-dimensional model construction is a new risk assessment method of morbillivirus infectivity. Because the method is applicable to animals that have no information about virus infection, it is especially useful for morbillivirus risk assessment and wildlife conservation.

  11. Estimating the Potential Impact of Canine Distemper Virus on the Amur Tiger Population (Panthera tigris altaica) in Russia

    PubMed Central

    Gilbert, Martin; Miquelle, Dale G.; Goodrich, John M.; Reeve, Richard; Cleaveland, Sarah; Matthews, Louise; Joly, Damien O.

    2014-01-01

    Lethal infections with canine distemper virus (CDV) have recently been diagnosed in Amur tigers (Panthera tigris altaica), but long-term implications for the population are unknown. This study evaluates the potential impact of CDV on a key tiger population in Sikhote-Alin Biosphere Zapovednik (SABZ), and assesses how CDV might influence the extinction potential of other tiger populations of varying sizes. An individual-based stochastic, SIRD (susceptible-infected-recovered/dead) model was used to simulate infection through predation of infected domestic dogs, and/or wild carnivores, and direct tiger-to-tiger transmission. CDV prevalence and effective contact based on published and observed data was used to define plausible low- and high-risk infection scenarios. CDV infection increased the 50-year extinction probability of tigers in SABZ by 6.3% to 55.8% compared to a control population, depending on risk scenario. The most significant factors influencing model outcome were virus prevalence in the reservoir population(s) and its effective contact rate with tigers. Adjustment of the mortality rate had a proportional impact, while inclusion of epizootic infection waves had negligible additional impact. Small populations were found to be disproportionately vulnerable to extinction through CDV infection. The 50-year extinction risk in populations consisting of 25 individuals was 1.65 times greater when CDV was present than that of control populations. The effects of density dependence do not protect an endangered population from the impacts of a multi-host pathogen, such as CDV, where they coexist with an abundant reservoir presenting a persistent threat. Awareness of CDV is a critical component of a successful tiger conservation management policy. PMID:25354196

  12. Genetically distant American Canine distemper virus lineages have recently caused epizootics with somewhat different characteristics in raccoons living around a large suburban zoo in the USA

    PubMed Central

    Lednicky, John A; Dubach, Jean; Kinsel, Michael J; Meehan, Thomas P; Bocchetta, Maurizio; Hungerford, Laura L; Sarich, Nicolene A; Witecki, Kelley E; Braid, Michael D; Pedrak, Casandra; Houde, Christiane M

    2004-01-01

    Background Mortality rates have differed during distemper outbreaks among free-ranging raccoons (Procyon lotor) living around a large Chicago-area zoo, and appeared higher in year 2001 than in 1998 and 2000. We hypothesized that a more lethal variant of the local Canine distemper virus (CDV) lineage had emerged in 2001, and sought the genetic basis that led to increased virulence. However, a more complex model surfaced during preliminary analyses of CDV genomic sequences in infected tissues and of virus isolated in vitro from the raccoons. Results Phylogenetic analyses of subgenomic CDV fusion (F) -, phosphoprotein (P) -, and complete hemagglutinin (H) – gene sequences indicated that distinct American CDV lineages caused the distemper epizootics. The 1998 outbreak was caused by viruses that are likely from an old CDV lineage that includes CDV Snyder Hill and Lederle, which are CDV strains from the early 1950's. The 2000 and 2001 viruses appear to stem from the lineage of CDV A75/17, which was isolated in the mid 1970's. Only the 2001 viruses formed large syncytia in brain and/or lung tissue, and during primary isolation in-vitro in Vero cells, demonstrating at least one phenotypic property by which they differed from the other viruses. Conclusions Two different American CDV lineages caused the raccoon distemper outbreaks. The 1998 viruses are genetically distant to the 2000/2001 viruses. Since CDV does not cause persistent infections, the cycling of different CDV lineages within the same locale suggests multiple reintroductions of the virus to area raccoons. Our findings establish a precedent for determining whether the perceived differences in mortality rates are actual and attributable in part to inherent differences between CDV strains arising from different CDV lineages. PMID:15507154

  13. 78 FR 29698 - Availability of an Environmental Assessment for Field Testing a Canine Lymphoma Vaccine, DNA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-21

    ... a Canine Lymphoma Vaccine, DNA AGENCY: Animal and Plant Health Inspection Service, USDA. ACTION... testing, and then to field test, an unlicensed Canine Lymphoma Vaccine, DNA. The environmental assessment... vaccine and related information, examines the potential effects that field testing this veterinary...

  14. Tumour necrosis factor-alpha-induced protein 8 (TNFAIP8) expression associated with cell survival and death in cancer cell lines infected with canine distemper virus.

    PubMed

    Garcia, J A; Ferreira, H L; Vieira, F V; Gameiro, R; Andrade, A L; Eugênio, F R; Flores, E F; Cardoso, T C

    2015-09-16

    Oncolytic virotherapy is a novel strategy for treatment of cancer in humans and companion animals as well. Canine distemper virus (CDV), a paramyxovirus, has proven to be oncolytic through induction of apoptosis in canine-derived tumour cells, yet the mechanism behind this inhibitory action is poorly understood. In this study, three human mammary tumour cell lines and one canine-derived adenofibrosarcoma cell line were tested regarding to their susceptibility to CDV infection, cell proliferation, apoptosis, mitochondrial membrane potential and expression of tumour necrosis factor-alpha-induced protein 8 (TNFAIP8). CDV replication-induced cytopathic effect, decrease of cell proliferation rates, and >45% of infected cells were considered death and/or under late apoptosis/necrosis. TNFAIP8 and CDVM gene expression were positively correlated in all cell lines. In addition, mitochondrial membrane depolarization was associated with increase in virus titres (p < 0.005). Thus, these results strongly suggest that both human and canine mammary tumour cells are potential candidates for studies concerning CDV-induced cancer therapy.

  15. Up-regulation of mRNA for matrix metalloproteinases-9 and -14 in advanced lesions of demyelinating canine distemper leukoencephalitis.

    PubMed

    Gröters, Sibylle; Alldinger, Susanne; Baumgärtner, Wolfgang

    2005-10-01

    demyelinating canine distemper leukoencephalitis.

  16. Host range and receptor utilization of canine distemper virus analyzed by recombinant viruses: Involvement of heparin-like molecule in CDV infection.

    PubMed

    Fujita, Kentaro; Miura, Ryuichi; Yoneda, Misako; Shimizu, Fusako; Sato, Hiroki; Muto, Yuri; Endo, Yasuyuki; Tsukiyama-Kohara, Kyoko; Kai, Chieko

    2007-03-15

    We constructed recombinant viruses expressing enhanced green fluorescent protein (EGFP) or firefly luciferase from cDNA clones of the canine distemper virus (CDV) (a Japanese field isolate, Yanaka strain). Using these viruses, we examined susceptibilities of different cell lines to CDV infection. The results revealed that the recombinant CDVs can infect a broad range of cell lines. Infectivity inhibition assay using a monoclonal antibody specific to the human SLAM molecule indicated that the infection of B95a cells with these recombinant CDVs is mainly mediated by SLAM but the infection of 293 cell lines with CDV is not, implying the presence of one or more alternative receptors for CDV in non-lymphoid tissue. Infection of 293 cells with the recombinant CDV was inhibited by soluble heparin, and the recombinant virus bound to immobilized heparin. Both F and H proteins of CDV could bind to immobilized heparin. These results suggest that heparin-like molecules are involved in CDV infection.

  17. Relationship between growth behavior in vero cells and the molecular characteristics of recent isolated classified in the Asia 1 and 2 groups of canine distemper virus.

    PubMed

    Lan, Nguyen Thi; Yamaguchi, Ryoji; Hirai, Takuya; Kai, Kazushige; Morishita, Kazuhiro

    2009-04-01

    Ten recent isolates of canine distemper virus (CDV) strains were classified according to the growth ability and development of syncytial cytopathic effects (CPE) in Vero cells. Strains P94S, Ac96I, S124C, MD231, MS232, MSA5 and 095Cr were classified as Type 1 and exhibited hardly and did not develop CPE in Vero cells. Strains 007Lm, 009L and 011C were classified as Type 2 as grew well but failed to develop a syncytial CPE in Vero cells. A comparison of the phylogenetic trees of the H and P genes showed that all Type 1 strains belonged to the Asia 1 group and all Type 2 strains belonged to the Asia 2 group. Our findings suggest that the recent Asia 2 isolated of CDV in Japan, but not Asia 1 may grow in Vero cells, and their growth ability may be related with their molecular characteristics.

  18. Caspase-3/-8/-9, Bax and Bcl-2 expression in the cerebellum, lymph nodes and leukocytes of dogs naturally infected with canine distemper virus.

    PubMed

    Del Puerto, H L; Martins, A S; Moro, L; Milsted, A; Alves, F; Braz, G F; Vasconcelos, A C

    2010-01-26

    Canine distemper is an immunosuppressive disease caused by the canine distemper virus (CDV). Pathogenesis mainly involves the central nervous system and immunosuppression. Dogs naturally infected with CDV develop apoptotic cells in lymphoid tissues and the cerebellum, but this apoptotic mechanism is not well characterized. To better understand this process, we evaluated the expression of Bax, Bcl-2, and caspase-3, -8 and -9, by evaluating mRNA levels in the peripheral blood, lymph nodes and cerebellum of CDV-infected (CDV+) and uninfected (CDV-) dogs by real-time polymerase chain reaction (PCR). Blood samples from 12 CDV+ and 8 CDV- dogs, diagnosed by reverse transcription-PCR, were subjected to hematological analysis and apoptotic gene expression was evaluated using real-time-PCR. Tissues from the cerebellum and lymph nodes of four CDV+ and three CDV-dogs were also subjected to real time-PCR. No significant differences were found between CDV+ and CDV- dogs in the hemotological results or in the expression of caspase-3, -8, -9, Bax, and Bcl-2 in the peripheral blood. However, expression of Bax, caspase-3, -8 and -9 was significantly higher in the cerebellum of CDV+ compared to CDV- dogs. Expression of caspase-3 and -8 was significantly higher in the lymph nodes of CDV+ compared to CDV- dogs. We concluded that infection with CDV induces apoptosis in the cerebellum and lymph nodes in different ways. Lymph node apoptosis apparently occurs via caspase-3 activation, through the caspase-8 pathway, and cerebellum apoptosis apparently occurs via caspase-3 activation, through the caspase-8 and mitochondrial pathways.

  19. Up-regulation of major histocompatibility complex class II antigen expression in the central nervous system of dogs with spontaneous canine distemper virus encephalitis.

    PubMed

    Alldinger, S; Wünschmann, A; Baumgärtner, W; Voss, C; Kremmer, E

    1996-09-01

    Major histocompatibility complex class II (MHC II) and canine distemper virus (CDV) antigen expression were compared by immunohistochemistry in the cerebellar white matter of ten dogs with naturally occurring canine distemper encephalitis. In addition, infiltrating mononuclear cells were characterized by employing poly- and monoclonal antibodies directed against human CD3, canine MHC II, CD5, B cell antigen and CDV-specific nucleoprotein. Positive antigen-antibody reaction was visualized by the avidin-biotin-peroxidase complex method on frozen sections. Histologically, neuropathological changes were categorized into acute, subacute, and chronic. In control brains, MHC II expression was weak and predominantly detected on resident microglia of the white matter and on endothelial, perivascular and intravascular cells. In CDV antigen-positive brains, MHC II was mainly found on microglia and to a lesser extent on endothelial, meningeal, choroid plexus epithelial, ependymal and intravascular cells. In addition, virtually all of the perivascular cells expressed MHC II antigen. CDV antigen was demonstrated most frequently in astrocytes. Of the perivascular lymphocytes, the majority were CD3-positive cells, followed by B cells. Only a small proportion of perivascular cells expressed the CD5 antigen. In addition, B cells and CD3 and CD5 antigen-positive cells were found occasionally in subacute and frequently in chronic demyelinating plaques. In acute encephalitis, CDV antigen exhibited a multifocal or diffuse distribution, and MHC II was moderately up-regulated throughout the white matter and accentuated in CDV antigen-positive plaques. In subacute encephalitis, moderate multifocal CDV antigen and moderate to strong diffuse MHC II-specific staining, especially prominent in CDV antigen-positive lesions, were observed. In chronic encephalitis, CDV antigen expression was restricted to single astrocytes at the edge of the lesions or was absent, while MHC II expression

  20. Canine distemper virus with the intact C protein has the potential to replicate in human epithelial cells by using human nectin4 as a receptor.

    PubMed

    Otsuki, Noriyuki; Sekizuka, Tsuyoshi; Seki, Fumio; Sakai, Kouji; Kubota, Toru; Nakatsu, Yuichiro; Chen, Surui; Fukuhara, Hideo; Maenaka, Katsumi; Yamaguchi, Ryoji; Kuroda, Makoto; Takeda, Makoto

    2013-01-20

    Recent outbreaks in monkeys have proven that canine distemper virus (CDV) causes diseases in a wide range of mammals. CDV uses SLAM and nectin4 as receptors to replicate in susceptible animals. Here, we show that human nectin4, but not human SLAM, is fully functional as a CDV receptor. The CDV Ac96I strain hardly replicated in nectin4-expressing human epithelial NCI-H358 cells, but readily adapted to grow in them. Unsurprisingly, no amino acid change in the H protein was required for the adaptation. The original Ac96I strain possessed a truncated C protein, and a subpopulation possessing the intact C protein was selected after growth in NCI-H358 cells. Other CDV strains possessing the intact C protein showed significantly higher growth abilities in NCI-H358 cells than the Ac96I strain with the truncated C protein. These findings suggest that the C protein is functional in human epithelial cells and critical for CDV replication in them.

  1. Gastric attaching and effacing Escherichia coli lesions in a puppy with naturally occurring enteric colibacillosis and concurrent canine distemper virus infection.

    PubMed

    Wada, Y; Kondo, H; Nakaoka, Y; Kubo, M

    1996-11-01

    A puppy suffering from chronic diarrhea was humanely killed at 90 days of age. Numerous Gram-negative bacilli were found adhering to the surface of as well as within epithelial cells from the stomach to the colon. Canine distemper virus inclusions were in the epithelial cytoplasm of the esophageal, gastric, and intestinal mucosa. Typical attaching and effacing ultrastructural lesions were in the stomach, and some bacilli were in the cytoplasm of the epithelial cells. Escherichia coli, isolated from the contents of the small intestine, belonged to serotype 0118: NM and were negative for plasmid-encoded EPEC adherence factor (EAF) and positive for the E. coli attaching effacing (eae) gene. Immunohistologically, bacilli attached to the epithelium from the stomach to the colon were positive for antisera against E. coli 0118. E. coli 0118: NM inoculated into human tissue culture cells (HEp-2 cells) were attached to the surface of the cells and within the cytoplasm. This is the first report of attaching and effacing E. coli (AEEC) infection in the stomach of the dog.

  2. Antibodies to CD9, a tetraspan transmembrane protein, inhibit canine distemper virus-induced cell-cell fusion but not virus-cell fusion.

    PubMed

    Schmid, E; Zurbriggen, A; Gassen, U; Rima, B; ter Meulen, V; Schneider-Schaulies, J

    2000-08-01

    Canine distemper virus (CDV) causes a life-threatening disease in several carnivores including domestic dogs. Recently, we identified a molecule, CD9, a member of the tetraspan transmembrane protein family, which facilitates, and antibodies to which inhibit, the infection of tissue culture cells with CDV (strain Onderstepoort). Here we describe that an anti-CD9 monoclonal antibody (MAb K41) did not interfere with binding of CDV to cells and uptake of virus. In addition, in single-step growth experiments, MAb K41 did not induce differences in the levels of viral mRNA and proteins. However, the virus release of syncytium-forming strains of CDV, the virus-induced cell-cell fusion in lytically infected cultures, and the cell-cell fusion of uninfected with persistently CDV-infected HeLa cells were strongly inhibited by MAb K41. These data indicate that anti-CD9 antibodies selectively block virus-induced cell-cell fusion, whereas virus-cell fusion is not affected.

  3. Exposure of Free-Ranging Wild Carnivores and Domestic Dogs to Canine Distemper Virus and Parvovirus in the Cerrado of Central Brazil.

    PubMed

    Furtado, Mariana Malzoni; Hayashi, Erika Midori Kida; Allendorf, Susan Dora; Coelho, Claudio José; de Almeida Jácomo, Anah Tereza; Megid, Jane; Ramos Filho, José Domingues; Silveira, Leandro; Tôrres, Natália Mundim; Ferreira Neto, José Soares

    2016-09-01

    Human population growth around protected areas increases the contact between wild and domestic animals, promoting disease transmission between them. This study investigates the exposure of free-ranging wild carnivores and domestic dogs to canine distemper virus (CDV) and parvovirus in Emas National Park (ENP) in the Cerrado savanna of central Brazil. Serum samples were collected from 169 wild carnivores, including the maned wolf (Chrysocyon brachyurus), crab-eating fox (Cerdocyon thous), hoary fox (Pseudalopex vetulus), puma (Puma concolor), ocelot (Leopardus pardalis), pampas cat (Leopardus colocolo), jaguarundi (Herpailurus yagouaroundi), striped hog-nosed skunk (Conepatus semistriatus) and coati (Nasua nasua), and from 35 domestic dogs living on rural properties bordering ENP. Serological tests showed that 10.6% of wild carnivores (maned wolves, crab-eating foxes and ocelots) and 71.4% of domestic dogs were exposed to CDV, and 56.8% of wild carnivores, including all species sampled except coatis, and 57.1% of domestic dogs were exposed to parvovirus. This report is the first to indicate that the free-ranging pampas cat, jaguarundi and striped hog-nosed skunk are exposed to parvovirus. CDV and parvovirus deserve attention in ENP, and it is extremely important to monitor the health of carnivore populations and perform molecular diagnosis of the viruses to determine the possible involvement of the domestic dog in their transmission.

  4. Infection with a Hepatozoon sp. closely related to Hepatozoon felis in a wild Pampas gray fox (Lycalopex -Pseudalopex -gymnocercus) co-infected with canine distemper virus.

    PubMed

    Giannitti, Federico; Diab, Santiago S; Uzal, Francisco A; Fresneda, Karina; Rossi, Daniel; Talmi-Frank, Dalit; Baneth, Gad

    2012-05-25

    A species of Hepatozoon closely related to Hepatozoon felis found in the skeletal and cardiac muscle of a wild Pampas gray fox (Lycalopex gymnocercus) is described. The fox was euthanized after showing severe incoordination. On necropsy and histopathology there was bilateral, diffuse, severe, sub-acute, necrotizing bronchointerstitial pneumonia, with intracytoplasmic and intranuclear eosinophilic inclusion bodies. Canine distemper virus was detected by immunohistochemistry in the bronchiolar epithelium, syncytial cells, alveolar macrophages and pneumocytes. The skeletal muscle and myocardium contained multiple round to oval protozoan cysts ranging from 64 μm × 75 μm to 98 μm × 122 μm, with a central eosinophilic meront-like core surrounded by concentric rings of mucinous material resembling Hepatozoon americanum cysts but smaller in size. Macrophages within rare pyogranulomas and monocytes/macrophages in adjacent sinusoidal blood vessels in the skeletal muscle contained intracytoplasmic round protozoa consistent with merozoites or developing gamonts of Hepatozoon. Hepatozoon sp. infection was confirmed by PCR of skeletal muscle and the sequenced 18S rRNA PCR product was found to be 99% identical to H. felis by BLAST analysis and deposited in GenBank as accession number HQ020489. It clustered together in the phylogenetic analysis with published H. felis sequences and separately from H. canis, H. americanum and other Hepatozoon species. However, the close relatedness of the fox Hepatozoon to H. felis does not rule out infection with a different and possibly unknown Hepatozoon species.

  5. The Fusion Protein Signal-Peptide-Coding Region of Canine Distemper Virus: A Useful Tool for Phylogenetic Reconstruction and Lineage Identification

    PubMed Central

    Sarute, Nicolás; Calderón, Marina Gallo; Pérez, Ruben; La Torre, José; Hernández, Martín; Francia, Lourdes; Panzera, Yanina

    2013-01-01

    Canine distemper virus (CDV; Paramyxoviridae, Morbillivirus) is the etiologic agent of a multisystemic infectious disease affecting all terrestrial carnivore families with high incidence and mortality in domestic dogs. Sequence analysis of the hemagglutinin (H) gene has been widely employed to characterize field strains, permitting the identification of nine CDV lineages worldwide. Recently, it has been established that the sequences of the fusion protein signal-peptide (Fsp) coding region are extremely variable, suggesting that analysis of its sequence might be useful for strain characterization studies. However, the divergence of Fsp sequences among worldwide strains and its phylogenetic resolution has not yet been evaluated. We constructed datasets containing the Fsp-coding region and H gene sequences of the same strains belonging to eight CDV lineages. Both datasets were used to evaluate their phylogenetic resolution. The phylogenetic analysis revealed that both datasets clustered the same strains into eight different branches, corresponding to CDV lineages. The inter-lineage amino acid divergence was fourfold greater for the Fsp peptide than for the H protein. The likelihood mapping revealed that both datasets display strong phylogenetic signals in the region of well-resolved topologies. These features indicate that Fsp-coding region sequence analysis is suitable for evolutionary studies as it allows for straightforward identification of CDV lineages. PMID:23675493

  6. Possible lin between elevated accumulation of trace elements and canine distemper virus infection in the Caspian seals (Phoca caspica) stranded in 2000 and 2001

    NASA Astrophysics Data System (ADS)

    Shinsuke, T.; Takashi, K.; Yasumi, A.; Tokutaka, I.; Reiji, K.

    2003-05-01

    In the Caspian Sea, a die-off of thousands of Caspian seals (Phoca caspica) occurred in 1997 and 2000. While a direct cause for these deaths seems to be canine distemper virus (CDV) infection, immunosuppression due to environmental pollutants is considered as one of the possible explanations for the development of the disease. The purpose of this work is to examine whether exposure to trace metals could be one of the factors involved in the mass mortality of Caspian seals. Concentrations of 13 trace elements weredetermined in liver, kidney and muscle of Caspian seals found stranded along the coasts of the Caspian Sea in 2000 and 2001. Concentrations of toxic elemen ts (Ag, Cd, Hg, Tl and Pb) in the Caspian seals collected in 2000 and 2001 were comparable to or lower than those in healthy Caspian seals collected in 1993 and 1998 and in seals from other regions, suggesting that these elements would not be the causative agent for the death of Caspian seals. In contrast, Zn and Fe concentrations in the stranded Caspian seals were apparently higher than those in seals from other locations. These results suggest the disturbance in homeostatic control and nutritional statu s of essential elements in the stranded Caspian seals.

  7. Immunohistochemical detection of autophagy-related microtubule-associated protein 1 light chain 3 (LC3) in the cerebellums of dogs naturally infected with canine distemper virus.

    PubMed

    Kabak, Y B; Sozmen, M; Yarim, M; Guvenc, T; Karayigit, M O; Gulbahar, M Y

    2015-01-01

    We investigated the expression of microtubule-associated protein 1 light chain 3 (LC3) protein in the cerebellums of dogs infected with canine distemper virus (CDV) using immunohistochemistry to detect autophagy. The cerebellums of 20 dogs infected with CDV were used. Specimens showing demyelination of white matter were considered to have an acute infection, whereas specimens showing signs of severe perivascular cuffing and demyelination of white matter were classified as having chronic CDV. Cerebellar sections were immunostained with CDV and LC3 antibodies. The cytoplasm of Purkinje cells, granular layer cells, motor neurons in large cerebellar ganglia and some neurons in white matter were positive for the LC3 antibody in both the control and CDV-infected dogs. In the infected cerebellums, however, white matter was immunostained more intensely, particularly the neurons and gemistocytic astrocytes in the demyelinated areas, compared to controls. Autophagy also was demonstrated in CDV-positive cells using double immunofluorescence staining. Our findings indicate that increased autophagy in the cerebellum of dogs naturally infected with CDV may play a role in transferring the virus from cell to cell.

  8. Canine Distemper Virus Infection Leads to an Inhibitory Phenotype of Monocyte-Derived Dendritic Cells In Vitro with Reduced Expression of Co-Stimulatory Molecules and Increased Interleukin-10 Transcription

    PubMed Central

    Herder, Vanessa; Stein, Veronika M.; Tipold, Andrea; Urhausen, Carola; Günzel-Apel, Anne-Rose; Rohn, Karl; Baumgärtner, Wolfgang; Beineke, Andreas

    2014-01-01

    Canine distemper virus (CDV) exhibits a profound lymphotropism that causes immunosuppression and increased susceptibility of affected dogs to opportunistic infections. Similar to human measles virus, CDV is supposed to inhibit terminal differentiation of dendritic cells (DCs), responsible for disturbed repopulation of lymphoid tissues and diminished antigen presenting function in dogs. In order to testify the hypothesis that CDV-infection leads to an impairment of professional antigen presenting cells, canine DCs have been generated from peripheral blood monocytes in vitro and infected with CDV. Virus infection was confirmed and quantified by transmission electron microscopy, CDV-specific immunofluorescence, and virus titration. Flow cytometric analyses revealed a significant down-regulation of the major histocompatibility complex class II and co-stimulatory molecules CD80 and CD86 in CDV-infected DCs, indicative of disturbed antigen presenting capacity. Molecular analyses revealed an increased expression of the immune inhibitory cytokine interleukin-10 in DCs following infection. Results of the present study demonstrate that CDV causes phenotypical changes and altered cytokine expression of DCs, which represent potential mechanisms to evade host immune responses and might contribute to immune dysfunction and virus persistence in canine distemper. PMID:24769532

  9. Canine distemper virus infection leads to an inhibitory phenotype of monocyte-derived dendritic cells in vitro with reduced expression of co-stimulatory molecules and increased interleukin-10 transcription.

    PubMed

    Qeska, Visar; Barthel, Yvonne; Herder, Vanessa; Stein, Veronika M; Tipold, Andrea; Urhausen, Carola; Günzel-Apel, Anne-Rose; Rohn, Karl; Baumgärtner, Wolfgang; Beineke, Andreas

    2014-01-01

    Canine distemper virus (CDV) exhibits a profound lymphotropism that causes immunosuppression and increased susceptibility of affected dogs to opportunistic infections. Similar to human measles virus, CDV is supposed to inhibit terminal differentiation of dendritic cells (DCs), responsible for disturbed repopulation of lymphoid tissues and diminished antigen presenting function in dogs. In order to testify the hypothesis that CDV-infection leads to an impairment of professional antigen presenting cells, canine DCs have been generated from peripheral blood monocytes in vitro and infected with CDV. Virus infection was confirmed and quantified by transmission electron microscopy, CDV-specific immunofluorescence, and virus titration. Flow cytometric analyses revealed a significant down-regulation of the major histocompatibility complex class II and co-stimulatory molecules CD80 and CD86 in CDV-infected DCs, indicative of disturbed antigen presenting capacity. Molecular analyses revealed an increased expression of the immune inhibitory cytokine interleukin-10 in DCs following infection. Results of the present study demonstrate that CDV causes phenotypical changes and altered cytokine expression of DCs, which represent potential mechanisms to evade host immune responses and might contribute to immune dysfunction and virus persistence in canine distemper.

  10. The Duration of Immunity to an Inactivated Adjuvanted Canine Parvovirus Vaccine. A 52 and 64 Week Postvaccination Challenge Study

    PubMed Central

    Povey, R. C.; Carman, P. S.; Ewert, E.

    1983-01-01

    Dogs were successfully isolated for a period of either 52 or 64 weeks following vaccination with an inactivated, adjuvanted canine parvovirus-2 vaccine. Antibody persisted in all ten vaccinated dogs, although in one case by 52 weeks postvaccination only virus neutralizing antibody, and not hemagglutination-inhibiting antibody, could be detected. Sentinel unvaccinated dogs housed alongside the vaccinated dogs throughout the study remained free of canine parvovirus-2 antibody until challenged. Upon oral challenge with canine parvovirus-2 infected material all unvaccinated dogs developed one or more signs of canine parvovirus-2 disease, shed virus and developed antibody. None of the vaccinated dogs became overtly sick. Of the five vaccinated dogs challenged 52 weeks after vaccination, three shed virus and one showed a significant rise in antibody. At 64 weeks after vaccination only one of the five challenged dogs shed virus and showed a boost in antibody titer. PMID:17422291

  11. Increased p75 neurotrophin receptor expression in the canine distemper virus model of multiple sclerosis identifies aldynoglial Schwann cells that emerge in response to axonal damage.

    PubMed

    Imbschweiler, Ilka; Seehusen, Frauke; Peck, Claas-Tido; Omar, Mohamed; Baumgärtner, Wolfgang; Wewetzer, Konstantin

    2012-03-01

    Gliogenesis under pathophysiological conditions is of particular clinical relevance since it may provide regeneration-promoting cells recruitable for therapeutic purposes. There is accumulating evidence that aldynoglial cells with Schwann cell-like growth-promoting properties emerge in the lesioned CNS. However, the characterization of these cells and the signals triggering their in situ generation have remained enigmatic. In the present study, we used the p75 neurotrophin receptor (p75(NTR) ) as a marker for Schwann cells to study gliogenesis in the well-defined canine distemper virus (CDV)-induced demyelination model. White matter lesions of CDV-infected dogs contained bi- to multipolar, p75(NTR) -expressing cells that neither expressed MBP, GFAP, BS-1, or P0 identifying oligodendroglia, astrocytes, microglia, and myelinating Schwann cells nor CDV antigen. Interestingly, p75(NTR) -expression became apparent prior to the onset of demyelination in parallel to the expression of β-amyloid precursor protein (β-APP), nonphosphorylated neurofilament (n-NF), BS-1, and CD3, and peaked in subacute lesions with inflammation. To study the role of infiltrating immune cells during differentiation of Schwann cell-like glia, organotypic slice cultures from the normal olfactory bulb were established. Despite the absence of infiltrating lymphocytes and macrophages, a massive appearance of p75(NTR) -positive Schwann-like cells and BS-1-positive microglia was noticed at 10 days in vitro. It is concluded that axonal damage as an early signal triggers the differentiation of tissue-resident precursor cells into p75(NTR) -expressing aldynoglial Schwann cells that retain an immature pre-myelin state. Further studies have to address the role of microglia during this process and the regenerative potential of aldynoglial cells in CDV infection and other demyelinating diseases.

  12. Phylogenetic analysis of the haemagglutinin gene of current wild-type canine distemper viruses from South Africa: lineage Africa.

    PubMed

    Woma, Timothy Y; van Vuuren, Moritz; Bosman, Ana-Mari; Quan, Melvyn; Oosthuizen, Marinda

    2010-07-14

    There are no reports of CDV isolations in southern Africa, and although CDV is said to have geographically distinct lineages, molecular information of African strains has not yet been documented. Viruses isolated in cell cultures were subjected to reverse transcription-polymerase chain reaction (RT-PCR), and the complete H gene was sequenced and phylogenetically analysed with other strains from GenBank. Phylogenetic comparisons of the complete H gene of CDV isolates from different parts of the world (available in GenBank) with wild-type South African isolates revealed nine clades. All South African isolates form a separate African clade of their own and thus are clearly separated from the American, European, Asian, Arctic and vaccine virus clades. It is likely that only the 'African lineage' of CDV may be circulating in South Africa currently, and the viruses isolated from dogs vaccinated against CDV are not the result of reversion to virulence of vaccine strains, but infection with wild-type strains.

  13. Longitudinal study of viruses associated with canine infectious respiratory disease.

    PubMed

    Erles, Kerstin; Dubovi, Edward J; Brooks, Harriet W; Brownlie, Joe

    2004-10-01

    In this investigation a population of dogs at a rehoming center was monitored over a period of 2 years. Despite regular vaccination of incoming dogs against distemper, canine adenovirus type 2 (CAV-2), and canine parainfluenza virus (CPIV), respiratory disease was endemic. Tissue samples from the respiratory tract as well as paired serum samples were collected for analysis. The development of PCR assays for the detection of CPIV, canine adenovirus types 1 and 2, and canine herpesvirus (CHV) is described. Surprisingly, canine adenovirus was not detected in samples from this population, whereas 19.4% of tracheal and 10.4% of lung samples were positive for CPIV and 12.8% of tracheal and 9.6% of lung samples were positive for CHV. As reported previously, a novel canine respiratory coronavirus (CRCoV) was detected in this population (K. Erles, C. Toomey, H. W. Brooks, and J. Brownlie, Virology 310:216-223, 2003). Infections with CRCoV occurred mostly during the first week of a dog's stay at the kennel, whereas CPIV and CHV were detected at later time points. Furthermore, the evaluation of an enzyme-linked immunosorbent assay for detection of antibodies to CPIV and an immunofluorescence assay for detection of antibodies to CHV is described. This study shows that CPIV is present at kennels despite vaccination. In addition, other agents such as CHV and CRCoV may play a role in the pathogenesis of canine respiratory disease, whereas CAV-2 and canine distemper virus were not present in this population, indicating that their prevalence in the United Kingdom is low due to widespread vaccination of dogs.

  14. Longitudinal Study of Viruses Associated with Canine Infectious Respiratory Disease

    PubMed Central

    Erles, Kerstin; Dubovi, Edward J.; Brooks, Harriet W.; Brownlie, Joe

    2004-01-01

    In this investigation a population of dogs at a rehoming center was monitored over a period of 2 years. Despite regular vaccination of incoming dogs against distemper, canine adenovirus type 2 (CAV-2), and canine parainfluenza virus (CPIV), respiratory disease was endemic. Tissue samples from the respiratory tract as well as paired serum samples were collected for analysis. The development of PCR assays for the detection of CPIV, canine adenovirus types 1 and 2, and canine herpesvirus (CHV) is described. Surprisingly, canine adenovirus was not detected in samples from this population, whereas 19.4% of tracheal and 10.4% of lung samples were positive for CPIV and 12.8% of tracheal and 9.6% of lung samples were positive for CHV. As reported previously, a novel canine respiratory coronavirus (CRCoV) was detected in this population (K. Erles, C. Toomey, H. W. Brooks, and J. Brownlie, Virology 310:216-223, 2003). Infections with CRCoV occurred mostly during the first week of a dog's stay at the kennel, whereas CPIV and CHV were detected at later time points. Furthermore, the evaluation of an enzyme-linked immunosorbent assay for detection of antibodies to CPIV and an immunofluorescence assay for detection of antibodies to CHV is described. This study shows that CPIV is present at kennels despite vaccination. In addition, other agents such as CHV and CRCoV may play a role in the pathogenesis of canine respiratory disease, whereas CAV-2 and canine distemper virus were not present in this population, indicating that their prevalence in the United Kingdom is low due to widespread vaccination of dogs. PMID:15472304

  15. Oligodendroglial degeneration in distemper: apoptosis or necrosis?

    PubMed

    Schobesberger, M; Zurbriggen, A; Summerfield, A; Vandevelde, M; Griot, C

    1999-03-01

    Canine distemper virus (CDV) causes a multifocal demyelinating disease in dogs. It was previously shown that the initial demyelinating lesions are directly virus induced since a correlation between the occurrence of demyelination and CDV replication in white matter cells was observed. During the course of infection oligodendrocytes undergo distinct morphological alterations, partly due to a restricted CDV infection of these cells, and eventually disappear from the lesions. This phenomenon has been described in vivo as well as in vitro. However, the reason for the morphological alterations and the following oligodendroglial depletion remained unclear. Since virus infection can induce cell death, it was investigated whether apoptosis or necrosis plays a role in the pathogenesis of demyelination in canine distemper. In brain tissue sections from dogs with acute distemper apoptotic cells were not detected within the demyelinating lesions using morphological and biochemical cell death criteria. In chronic distemper, apoptotic cells - presumably inflammatory cells - were seen within the perivascular cuffs. These in vivo findings were correlated to the in vitro situation using CDV-infected primary dog brain cell cultures as well as Vero cells. Infection with culture-adapted CDV lead to massive necrosis but not to apoptosis. After infection with virulent CDV neither apoptosis nor necrosis was a predominant feature in either culture system. These findings suggest that virus-induced demyelination in canine distemper is not the direct consequence of apoptosis or necrosis. It is speculated that another mechanism must be responsible for the observed morphological alterations of oligodendrocytes, ultimately leading to demyelination.

  16. Effective primary isolation of wild-type canine distemper virus in MDCK, MV1 Lu and Vero cells without nucleotide sequence changes within the entire haemagglutinin protein gene and in subgenomic sections of the fusion and phospho protein genes.

    PubMed

    Lednicky, John A; Meehan, Thomas P; Kinsel, Michael J; Dubach, Jean; Hungerford, Laura L; Sarich, Nicolene A; Witecki, Kelley E; Braid, Michael D; Pedrak, Casandra; Houde, Christiane M

    2004-06-15

    Canine distemper virus (CDV) is an important pathogen of many carnivores. We are developing a field-based model of morbillivirus virulence and pathogenesis through a study of distemper in naturally infected free-ranging raccoons. The isolation of CDV from raccoon tissues is essential for this work. CDV has often been isolated from animals only after co-cultivation of infected tissues with peripheral blood mononuclear cells derived from specific pathogen-free dogs or similar methods. We explored the utility and consequences of a simpler and cheaper alternative: CDV isolation in Vero, MDCK, and MV1 Lu cells. Virus growth was detected first in MDCK cells, whereas viral cytopathic effects were most obvious in Vero cells. CDV growth in MV1 Lu cells was relatively protracted and occurred without the formation of cytopathic effects. In primary CDV isolates, the entire nucleotide sequence of the receptor binding haemagglutinin (H) gene, and subgenomic fusion (F) and phospho (P) protein gene sequences corresponding to nt 5399-5733 and 2132-2563 of CDV reference strain Onderstepoort, respectively, were identical to those in matched infected tissues. Virus isolation confirmed the presence of CDV in instances where RT-PCR failed to detect CDV in infected tissues. Different viral phenotypes and genotypes were detected. The conservation of H gene sequences in primary CDV isolates suggests that MDCK, MV1 Lu, and Vero cells express proper receptors for wild-type CDV.

  17. Use of quantitative real-time RT-PCR to investigate the correlation between viremia and viral shedding of canine distemper virus, and infection outcomes in experimentally infected dogs.

    PubMed

    Sehata, Go; Sato, Hiroaki; Ito, Toshihiro; Imaizumi, Yoshitaka; Noro, Taichi; Oishi, Eiji

    2015-07-01

    We used real-time RT-PCR and virus titration to examine canine distemper virus (CDV) kinetics in peripheral blood and rectal and nasal secretions from 12 experimentally infected dogs. Real-time RT-PCR proved extremely sensitive, and the correlation between the two methods for rectal and nasal (r=0.78, 0.80) samples on the peak day of viral RNA was good. Although the dogs showed diverse symptoms, viral RNA kinetics were similar; the peak of viral RNA in the symptomatic dogs was consistent with the onset of symptoms. These results indicate that real-time RT-PCR is sufficiently sensitive to monitor CDV replication in experimentally infected dogs regardless of the degree of clinical manifestation and suggest that the peak of viral RNA reflects active CDV replication.

  18. Chicken HSP70 DNA vaccine inhibits tumor growth in a canine cancer model.

    PubMed

    Yu, Wen-Ying; Chuang, Tien-Fu; Guichard, Cécile; El-Garch, Hanane; Tierny, Dominique; Laio, Albert Taiching; Lin, Ching-Si; Chiou, Kuo-Hao; Tsai, Cheng-Long; Liu, Chen-Hsuan; Li, Wen-Chiuan; Fischer, Laurent; Chu, Rea-Min

    2011-04-18

    Immunization with xenogeneic DNA is a promising cancer treatment to overcome tolerance to self-antigens. Heat shock protein 70 (HSP70) is over-expressed in various kinds of tumors and is believed to be involved in tumor progression. This study tested a xenogeneic chicken HSP70 (chHSP70) DNA vaccine in an experimental canine transmissible venereal tumor (CTVT) model. Three vaccination strategies were compared: the first (PE) was designed to evaluate the prophylactic efficacy of chHSP70 DNA vaccination by delivering the vaccine before tumor inoculation in a prime boost setting, the second (T) was designed to evaluate the therapeutic efficacy of the same prime boost vaccine by vaccinating the dogs after tumor inoculation; the third (PT) was similar to the first strategy (PE), with the exception that the electroporation booster injection was replaced with a transdermal needle-free injection. Tumor growth was notably inhibited only in the PE dogs, in which the vaccination program triggered tumor regression significantly sooner than in control dogs (NT). The CD4(+) subpopulation of tumor-infiltrating lymphocytes and canine HSP70 (caHSP70)-specific IFN-γ-secreting lymphocytes were significantly increased during tumor regression in the PE dogs as compared to control dogs, demonstrating that specific tolerance to caHSP70 has been overcome. In contrast, no benefit of the therapeutic strategy (T) could be noticed and the (PT) strategy only led to partial control of tumor growth. In summary, antitumor prophylactic activity was demonstrated using the chHSP70 DNA vaccine including a boost via electroporation. Our data stressed the importance of DNA electroporation as a booster to get the full benefit of DNA vaccination but also of cancer immunotherapy initiation as early as possible. Xenogeneic chHSP70 DNA vaccination including an electroporation boost is a potential vaccine to HSP70-expressing tumors, although further research is still required to better understand true

  19. Immunological changes in canine peripheral blood leukocytes triggered by immunization with first or second generation vaccines against canine visceral leishmaniasis.

    PubMed

    Araújo, Márcio Sobreira Silva; de Andrade, Renata Aline; Sathler-Avelar, Renato; Magalhães, Camila Paula; Carvalho, Andréa Teixeira; Andrade, Mariléia Chaves; Campolina, Sabrina Sidney; Mello, Maria Norma; Vianna, Leonardo Rocha; Mayrink, Wilson; Reis, Alexandre Barbosa; Malaquias, Luiz Cosme Cotta; Rocha, Luciana Morais; Martins-Filho, Olindo Assis

    2011-05-15

    In this study, we summarized the major phenotypic/functional aspects of circulating leukocytes following canine immunization with Leishvaccine and Leishmune®. Our findings showed that Leishvaccine triggered early changes in the innate immunity (neutrophils and eosinophils) with late alterations on monocytes. Conversely, Leishmune(®) induced early phenotypic changes in both, neutrophils and monocytes. Moreover, Leishvaccine triggered mixed activation-related phenotypic changes on T-cells (CD4+ and CD8+ and B-lymphocytes, whereas Leishmune(®) promoted a selective response, mainly associated with CD8+ T-cell activation. Mixed cytokine profile (IFN-γ/IL-4) was observed in Leishvaccine immunized dogs whereas a selective pro-inflammatory pattern (IFN-γ/NO) was induced by Leishmune® vaccination. The distinct immunological profile triggered by Leishvaccine and Leishmune® may be a direct consequence of the distinct biochemical composition of these immunobiological, i.e. complex versus purified Leishmania antigen along with Bacillus Calmette-Guérin (BCG) versus saponin adjuvant. Both immunobiologicals are able to activate phagocytes and CD8+ T-cells and therefore could be considered as a putative vaccines against canine visceral leishmaniasis (CVL).

  20. Combined distemper-adenoviral pneumonia in a dog.

    PubMed

    Rodriguez-Tovar, Luis E; Ramírez-Romero, Rafael; Valdez-Nava, Yazel; Nevárez-Garza, Alicia M; Zárate-Ramos, Juan J; López, Alfonso

    2007-06-01

    A 3 1/2-month-old pug with oculonasal discharge and seizures was submitted for postmortem examination. Grossly, the lungs had cranioventral consolidation, and microscopically, 2 distinct types of inclusion bodies compatible with Canine distemper virus and Canine adenovirus type 2. Presence of both viruses was confirmed via immunohistochemical staining.

  1. Combined distemper-adenoviral pneumonia in a dog

    PubMed Central

    Rodriguez-Tovar, Luis E.; Ramírez-Romero, Rafael; Valdez-Nava, Yazel; Nevárez-Garza, Alicia M.; Zárate-Ramos, Juan J.; López, Alfonso

    2007-01-01

    A 3 1/2-month-old pug with oculonasal discharge and seizures was submitted for postmortem examination. Grossly, the lungs had cranioventral consolidation, and microscopically, 2 distinct types of inclusion bodies compatible with Canine distemper virus and Canine adenovirus type 2. Presence of both viruses was confirmed via immunohistochemical staining. PMID:17616064

  2. Development of recombinant nucleocapsid protein based IgM-ELISA for the early detection of distemper infection in dogs.

    PubMed

    Latha, D; Geetha, M; Ramadass, P; Narayanan, R B

    2007-10-15

    An IgM-ELISA based on a 16-kDa recombinant protein produced for the conserved and functional middle region of nucleocapsid protein of Canine distemper virus was developed. Out of 70 serum samples from distemper-suspected and vaccinated dogs analyzed, 34 serum samples (49%) were positive. The specificity of this ELISA was confirmed by blocking and adsorption experiments. The IgM-ELISA based on the recombinant nucleocapsid protein showed a strong correlation (r=0.857, p<0.0001 at 95% CI) and good agreement (kappa=0.714) with the conventional Vero cell culture distemper antigen based IgM-ELISA. The percent positivity was more in dogs with systemic signs (62%) by recombinant nucleocapsid protein IgM-ELISA. Out of 70 clinical serum samples, 69 samples were used along with 4 control sera used in the IgM-ELISA for the detection of viral RNA by Slot blot hybridization and 26 of them (36%) were positive. Fifty-one percent agreement was observed between the recombinant nucleocapsid protein IgM-ELISA and Slot blot hybridization. The analysis of clinical history of the dogs with systemic signs supported the application of IgM-ELISA over Slot blot hybridization in the early detection of distemper infection.

  3. Dogs, distemper and Paget's disease.

    PubMed

    Mee, A P; Sharpe, P T

    1993-12-01

    The cause of Paget's disease is still unknown, despite many years of intensive study. During this time, evidence has sporadically emerged to suggest that the disease may result from a slow viral infection by one or more of the Paramyxoviruses. More recently, epidemiologic and molecular studies have suggested that the canine paramyxovirus, canine distemper virus, is the virus responsible for the disease. If true, then along with rabies, this would be a further example of a canine virus causing human disease. Studies in the natural host have now supported these findings. Further investigations have proposed that the bony abnormalities seen in Paget's disease are due to the effects of the virus on osteoclastic interleukin-6 and c-FOS production, possibly via the transcription factor NF-kappa B.

  4. Evaluation of an attenuated strain of Ehrlichia canis as a vaccine for canine monocytic ehrlichiosis.

    PubMed

    Rudoler, Nir; Baneth, Gad; Eyal, Osnat; van Straten, Michael; Harrus, Shimon

    2012-12-17

    Canine monocytic ehrlichiosis is an important tick-borne disease worldwide. No commercial vaccine for the disease is currently available and tick control is the main preventive measure against the disease. The aim of this study was to evaluate the potential of a multi-passaged attenuated strain of Ehrlichia canis to serve as a vaccine for canine monocytic ehrlichiosis, and to assess the use of azithromycin in the treatment of acute ehrlichiosis. Twelve beagle dogs were divided into 3 groups of 4 dogs. Groups 1 and 2 were inoculated (vaccinated) with an attenuated strain of E. canis (#611A) twice or once, respectively. The third group consisted of naïve dogs which served as controls. All 3 groups were challenged with a wild virulent strain of E. canis by administering infected dog-blood intravenously. Transient thrombocytopenia was the only hematological abnormality observed following inoculation of dogs with the attenuated strain. Challenge with the virulent strain resulted in severe disease in all 4 control dogs while only 3 of 8 vaccinated dogs presented mild transient fever. Furthermore, the mean blood rickettsial load was significantly higher in the control group (27-92-folds higher during days 14-19 post challenge with the wild the strain) as compared to the vaccinated dogs. The use of azithromycin was assessed as a therapeutic agent for the acute disease. Four days treatment resulted in further deterioration of the clinical condition of the dogs. Molecular comparison of 4 genes known to express immunoreactive proteins and virulence factors (p30, gp19, VirB4 and VirB9) between the attenuated strain and the challenge wild strain revealed no genetic differences between the strains. The results of this study indicate that the attenuated E. canis strain may serve as an effective and secure future vaccine for canine ehrlichiosis.

  5. Oral immunization of raccoons and skunks with a canine adenovirus recombinant rabies vaccine.

    PubMed

    Henderson, Heather; Jackson, Felix; Bean, Kayla; Panasuk, Brian; Niezgoda, Michael; Slate, Dennis; Li, Jianwei; Dietzschold, Bernard; Mattis, Jeff; Rupprecht, Charles E

    2009-11-27

    Oral vaccination is an important part of wildlife rabies control programs. Currently, the vaccinia-rabies glycoprotein recombinant virus is the only oral rabies vaccine licensed in the United States, and it is not effective in skunks. In the current study, captive raccoons and skunks were used to evaluate a vaccine developed by incorporating the rabies virus glycoprotein gene into a canine adenovirus serotype 2 vector (CAV2-RVG). Seven of 7 raccoons orally vaccinated with CAV2-RVG developed virus neutralizing antibodies and survived lethal challenge. Five of 5 and 6 of 6 skunks in 2 experimental groups receiving 10-fold different dilutions of CAV2-RVG developed neutralizing antibodies and survived challenge. The results of this preliminary study suggest that CAV2-RVG stimulates protective immunity against rabies in raccoons and skunks.

  6. Canine infectious tracheobronchitis: effects of an intranasal live canine parainfluenza-Bordetella bronchiseptica vaccine on viral shedding and clinical tracheobronchitis (kennel cough).

    PubMed

    Kontor, E J; Wegrzyn, R J; Goodnow, R A

    1981-10-01

    A modified-live intranasal (IN) canine parainfluenza (CPI)-virus Bordetella bronchiseptica vaccine was evaluated in dogs for efficacy against laboratory-induced canine infectious tracheobronchitis. The comparative efficacies of IN and parenteral administrations of the CPI virus fraction were also evaluated. The frequency and duration of clinical tracheobronchitis, blood serum agglutination titer, humoral antibody response, and duration of CPI virus and B bronchiseptica shedding were measured. Group A dogs were vaccinated subcutaneously or IM with an experimental CPI vaccine and challenge exposed with CPI virus. Group B dogs were vaccinated IN with avirulent CPI virus-B bronchiseptica live antigens and challenge exposed with virulent CPI virus and virulent B bronchiseptica. The IN vaccination (group B) significantly reduced (P less than or equal to 0.001) the occurrence of clinical tracheobronchitis by 96%. The combined challenge exposure of virulent CPI and virulent B bronchiseptica produced a synergistic enhancement of the clinical signs of kennel cough. The percentage of days after challenge exposure that virus shedding was detected for controls equaled 70% as compared with 50% and only 1% for parenterally and IN vaccinated dogs, respectively. Isolation of virulent B bronchiseptica microorganisms was reduced 89% in dogs vaccinated IN compared to controls. The geometric mean humoral antibody titers to CPI virus after 2 parenteral vaccinations and 1 IN vaccination were 1:43 and 1:34, respectively.

  7. Prevalence of antibodies to canine parvovirus and reaction to vaccination in client-owned, healthy dogs.

    PubMed

    Riedl, M; Truyen, U; Reese, S; Hartmann, K

    2015-12-12

    The purpose of this population-based cohort study was to assess current prevalence of antibodies to canine parvovirus (CPV) in adult, healthy dogs, including risk factors associated with lack of antibodies, and reaction to revaccination with a modified live vaccine (MLV). One hundred dogs routinely presented for vaccination were included in the study and vaccinated with a single dose of a combined MLV. Information was collected on signalment, origin, environment, vaccination history and side effects. Prevaccination and postvaccination antibodies were detected by haemagglutination inhibition. Univariate analysis, followed by multivariate logistic regression, was used to investigate association between different variables and presence of antibodies as well as titre increase. Protective CPV antibodies were present in 86.0 per cent of dogs. Intervals of more than four years since the last vaccination and rare contacts with other dogs were determined as main risk factors for the absence of antibodies. An increase in titres only occurred in 17.0 per cent of dogs. Dogs without protective titres before vaccination or with bodyweight <10 kg were more likely to have an adequate titre increase. Based on these findings, antibody status should be determined instead of periodic vaccinations to ensure reliable protection without unnecessary vaccinations in adult dogs.

  8. Evolution of canine parvovirus--a need for new vaccines?

    PubMed

    Truyen, Uwe

    2006-10-05

    Canine parvovirus (CPV) is a new virus, which is continuing to evolve, giving rise to new antigenic types and virus mutants that spread through the dog population. The most successful mutants, from an evolutionary perspective, appear to be selected by improved binding to the CPV receptor, the canine transferrin receptor, and by an extended host range, which for the newer antigenic types now includes both the dog and the cat. The new viruses also show antigenic differences that can be defined by binding of certain monoclonal antibodies; they also differ in their reactivity in virus neutralisation tests, using immune sera raised against the various antigenic types. These differences may influence the susceptibility of young animals to infection at the time when the level of maternally derived antibody decreases to the minimum protective titre. This minimum protective titre may vary depending on the infecting virus type. There is, however, a high degree of cross-protection between the virus types and the true relevance of the differences in neutralisation titer is currently not known.

  9. Temperature-Sensitive Live-Attenuated Canine Influenza Virus H3N8 Vaccine.

    PubMed

    Nogales, Aitor; Rodriguez, Laura; Chauché, Caroline; Huang, Kai; Reilly, Emma C; Topham, David J; Murcia, Pablo R; Parrish, Colin R; Martínez-Sobrido, Luis

    2017-02-15

    Canine influenza is a respiratory disease of dogs caused by canine influenza virus (CIV). CIV subtypes responsible for influenza in dogs include H3N8, which originated from the transfer of H3N8 equine influenza virus to dogs; and the H3N2 CIV, which is an avian-origin virus that adapted to infect dogs. Influenza infections are most effectively prevented through vaccination to reduce transmission and future infection. Currently, only inactivated influenza vaccines (IIVs) are available for the prevention of CIV in dogs. However, the efficacy of IIVs is suboptimal, and novel approaches are necessary for the prevention of disease caused by this canine respiratory pathogen. Using reverse genetics techniques, we have developed a live-attenuated CIV vaccine (LACIV) for the prevention of H3N8 CIV. The H3N8 LACIV replicates efficiently in canine cells at 33°C but is impaired at temperatures of 37 to 39°C and was attenuated compared to wild-type H3N8 CIV in vivo and ex vivo The LACIV was able to induce protection against H3N8 CIV challenge with a single intranasal inoculation in mice. Immunogenicity and protection efficacy were better than that observed with a commercial CIV H3N8 IIV but provided limited cross-reactive immunity and heterologous protection against H3N2 CIV. These results demonstrate the feasibility of implementing a LAIV approach for the prevention and control of H3N8 CIV in dogs and suggest the need for a new LAIV for the control of H3N2 CIV.

  10. Immunogenicity assay of the Leishmune vaccine against canine visceral leishmaniasis in Brazil.

    PubMed

    Borja-Cabrera, G P; Santos, F N; Bauer, F S; Parra, L E; Menz, I; Morgado, A A; Soares, I S; Batista, L M M; Palatnik-de-Sousa, C B

    2008-09-15

    Leishmune is the industrialized version of the FML-saponin vaccine which has been shown to develop 92-95% protection in vaccinated dogs and 76-80% vaccine efficacy against field canine visceral leishmaniasis (CVL) in Brazil. Leishmune has been proven to be safe and tolerable and a transmission-blocking vaccine which renders vaccinated dogs non-infectious to sand fly vectors. In the present investigation, 550 healthy seronegative dogs of endemic and epidemic areas of Brazil were monitored for Leishmune-induced immunogenicity during a 2-year trial. Another group of 588 untreated exposed dogs was also studied in parallel. Both groups were seronegative on day 0. The strong immunogenicity induced by Leishmune vaccine was demonstrated by the 98% of FML-seroconversion, increase in absorbencies, the 82.7% DTH positive reactions and increase in skin test size diameters, the average increase in CD8+ total lymphocytes population in blood (27.1%), expected for QS21 saponin-containing vaccine, the sustained proportions of CD4+ T cells, and the average increased proportions of CD21+ B lymphocytes (42.3%). The Leishmune-induced protection against CVL is demonstrated by the results: 98.8% asymptomatic dogs (at the end of first year) and 99% healthy survivors (at the end of the second year) among vaccinated dogs, compared to the 79.4% asymptomatic and 61% survivor dogs (p<0.001) monitored in the untreated exposed cohort. In spite of the low vaccine coverage, it was possible to detect a 66.1% (p<0.005) reduction in Belo Horizonte and an 80.2% (p<0.005) reduction in Araçatuba of the incidence of CVL among vaccinated dogs, when compared to the global incidence of CVL of each town, respectively. Our preliminary results support the potential use of Leishmune to prevent CVL epidemics.

  11. Coverage of pilot parenteral vaccination campaign against canine rabies in N'Djaména, Chad.

    PubMed Central

    Kayali, U.; Mindekem, R.; Yémadji, N.; Vounatsou, P.; Kaninga, Y.; Ndoutamia, A. G.; Zinsstag, J.

    2003-01-01

    Canine rabies, and thus human exposure to rabies, can be controlled through mass vaccination of the animal reservoir if dog owners are willing to cooperate. Inaccessible, ownerless dogs, however, reduce the vaccination coverage achieved in parenteral campaigns. This study aimed to estimate the vaccination coverage in dogs in three study zones of N'Djaména, Chad, after a pilot free parenteral mass vaccination campaign against rabies. We used a capture-mark-recapture approach for population estimates, with a Bayesian, Markov chain, Monte Carlo method to estimate the total number of owned dogs, and the ratio of ownerless to owned dogs to calculate vaccination coverage. When we took into account ownerless dogs, the vaccination coverage in the dog populations was 87% (95% confidence interval (CI), 84-89%) in study zone I, 71% (95% CI, 64-76%) in zone II, and 64% (95% CI, 58-71%) in zone III. The proportions of ownerless dogs to owned dogs were 1.1% (95% CI, 0-3.1%), 7.6% (95% CI, 0.7-16.5%), and 10.6% (95% CI, 1.6-19.1%) in the three study zones, respectively. Vaccination coverage in the three populations of owned dogs was 88% (95% CI, 84-92%) in zone I, 76% (95% CI, 71-81%) in zone II, and 70% (95% CI, 66-76%) in zone III. Participation of dog owners in the free campaign was high, and the number of inaccessible ownerless dogs was low. High levels of vaccination coverage could be achieved with parenteral mass vaccination. Regular parenteral vaccination campaigns to cover all of N'Djaména should be considered as an ethical way of preventing human rabies when post-exposure treatment is of limited availability and high in cost. PMID:14758434

  12. Immunogenicity of a DNA-launched replicon-based canine parvovirus DNA vaccine expressing VP2 antigen in dogs.

    PubMed

    Dahiya, Shyam S; Saini, Mohini; Kumar, Pankaj; Gupta, Praveen K

    2012-10-01

    A replicon-based DNA vaccine encoding VP2 gene of canine parvovirus (CPV) was developed by cloning CPV-VP2 gene into a replicon-based DNA vaccine vector (pAlpha). The characteristics of a replicon-based DNA vaccine like, self-amplification of transcripts and induction of apoptosis were analyzed in transfected mammalian cells. When the pAlpha-CPV-VP2 was injected intradermal as DNA-launched replicon-based DNA vaccine in dogs, it induced CPV-specific humoral and cell mediated immune responses. The virus neutralization antibody and lymphocyte proliferative responses were higher than conventional CPV DNA vaccine and commercial CPV vaccine. These results indicated that DNA-launched replicon-based CPV DNA vaccine was effective in inducing both CPV-specific humoral and cellular immune responses and can be considered as effective alternative to conventional CPV DNA vaccine and commercial CPV vaccine.

  13. Detection by PCR of wild-type canine parvovirus which contaminates dog vaccines.

    PubMed Central

    Senda, M; Parrish, C R; Harasawa, R; Gamoh, K; Muramatsu, M; Hirayama, N; Itoh, O

    1995-01-01

    A method for detecting wild-type canine parvovirus (CPV) strains which contaminate vaccines for dogs has been developed by PCR. PCR primers which distinguish vaccine strains from the most common, recent strains of wild-type CPV in many countries, including Japan and the United States, were developed. This PCR is based on the differences in nucleotide sequences which determine the two antigenic types of this virus. CPV vaccine strains derived from antigenically old-type virus prevalent in former times were not detected by PCR with differential primers. Detection sensitivity of PCR was 100- to 10,000-fold higher than that of the culture method in Crandell feline kidney cells. PMID:7699026

  14. Safety trial using the Leishmune vaccine against canine visceral leishmaniasis in Brazil.

    PubMed

    Parra, L E; Borja-Cabrera, G P; Santos, F N; Souza, L O P; Palatnik-de-Sousa, C B; Menz, I

    2007-03-08

    A group of 600 healthy and asymptomatic dogs from Brazilian canine visceral leishmaniasis endemic areas was vaccinated with three sc doses of Leishmune which is the industrialized formulation of the FML-saponin, recently licensed for commercialization in Brazil, which previously showed 76-80% vaccine efficacy against canine visceral leishmaniasis. Safety evaluation was performed for 14 days after each vaccine injection and disclosed transient reactions of local pain (40.87%), anorexia (20.48%), apathy (24.17%), local swelling reactions (15.90%), vomit (2.4%) and diarrhoea (1.5%). All effects showed significantly correlating declines, from the first to the third dose (p<0.0001). Most of the noticed reactions of pain (73%), anorexia (79%) and local swelling (84.7%) were mild. No significant differences between puppies and adults dogs were found in the number of adverse reactions. Adult dogs developed however, 94.5% of the small swelling reactions (<3 cm), and indicating that they are more resistant to the inflammatory response promoted by the saponins. No dead by anaphylaxis occurred, and only two dogs (0.1%) showed allergic reactions (facial oedema and itching) after the third dose. Transient alopecia on injection site occurred in only five poodles (0.28%) with total recovery and no need of treatment. All the mild adverse events in response to Leishmune injection were transient and disappeared before the injection of the following vaccine dose, confirming the tolerability of the vaccine. The Leishmune preparation was less haemolytic (HD(50)=180 microg/ml) than expected for a QS21 saponin-containing vaccine, indicating that its formulation with the FML antigen diminished the potential in vitro toxicity.

  15. Apoptosis in the cerebellum of dogs with distemper.

    PubMed

    Moro, L; Martins, A S; Alves, C M; Santos, F G A; Del Puerto, H L; Vasconcelos, A C

    2003-06-01

    Canine distemper virus (CDV) may induce multifocal demyelination in the central nervous system of infected dogs. The pathogenesis of this process is not clear. The present work identifies the presence of apoptotic cells in white and grey matter of dogs'cerebellum, naturally infected with CDV. Fifteen dogs with clinical signs of canine distemper that tested positive for CDV nucleoprotein were used. Brain specimens were processed and embedded in paraffin. Sections 5 microm thick were stained with hematoxylin-eosin and Shorr. Other sections were submitted to TUNEL reaction and to immunohistochemistry for CDV nucleoprotein detection. Acute and chronic demyelinated plaques were observed in the white matter, while apoptosis occurred particularly in the granular layer of grey matter. Apoptosis seems to play an important role in the pathogenesis of canine distemper demyelination.

  16. Serological responses of adult dogs to revaccination against distemper, parvovirus and rabies.

    PubMed

    Ottiger, H-P; Neimeier-Förster, M; Stärk, K D C; Duchow, K; Bruckner, L

    2006-07-01

    Serum antibody titres to canine distemper virus (CDV), canine parvovirus (CPV) and rabies were measured in dogs that had not been revaccinated annually and compared with the titres in a control group of regularly vaccinated animals; 83 per cent (171 of 207) of the dogs vaccinated against CDV one or more years earlier had serum neutralising antibody titres equal to or greater than 16; 64 per cent (136 of 213) of the dogs vaccinated against CPV one or more years earlier had haemagglutination inhibiting titres equal to or greater than 80; and 59 per cent (46 of 78) of the dogs vaccinated against rabies two or more years earlier had serum neutralising antibody titres equal to or greater than 0.5 iu/ml. Three weeks after a single booster vaccination the dogs' antibody titres against CDV had increased above the threshold level in 94 per cent of the dogs, against CPV in 68 per cent, and against rabies in 100 per cent.

  17. Decrease of the incidence of human and canine visceral leishmaniasis after dog vaccination with Leishmune in Brazilian endemic areas.

    PubMed

    Palatnik-de-Sousa, Clarisa B; Silva-Antunes, Ilce; Morgado, Adilson de Aguiar; Menz, Ingrid; Palatnik, Marcos; Lavor, Carlile

    2009-06-02

    Leishmune, the first prophylactic vaccine licensed against canine visceral leishmaniasis (CVL), has been used in Brazil since 2004, where seropositive dogs are sacrificed in order to control human visceral leishmaniasis (VL). We demonstrate here that vaccination with Leishmune does not interfere with the serological control campaign (110,000 dogs). Only 1.3% of positivity (76 among 5860) was detected among Leishmune uninfected vaccinees. We also analyzed the possible additive effect of Leishmune vaccination over dog culling, on the decrease of the incidence of CVL and VL in two Brazilian endemic areas, from 2004 to 2006. In Araçatuba, a 25% of decline was seen in CVL with a 61% decline in human cases, indicating the additive effect of Leishmune vaccination of 5.7% of the healthy dogs (1419 dogs), on regular dog culling. In Belo Horizonte (BH), rising curves of canine and human incidence were observed in the districts of Barreiro, Venda Nova and Noroeste, while the canine and human incidence of Centro Sul, Leste, Nordeste, Norte, Pampulha and Oeste, started to decrease or maintained a stabilized plateau after Leishmune vaccination. Among the districts showing a percent decrease of human incidence (-36.5%), Centro Sul and Pampulha showed the highest dog vaccination percents (63.27% and 27.27%, respectively) and the lowest dog incidence (-3.36% and 1.89%, respectively). They were followed by Oeste, that vaccinated 25.30% of the animals and experienced an increase of only 12.86% of dog incidence and by Leste and Nordeste, with lower proportions of vaccinees (11.72% and 10.76%, respectively) and probably because of that, slightly higher canine incidences (42.77% and 35.73%). The only exception was found in Norte district where the reduced human and canine incidence were not correlated to Leishmune vaccination. Much lower proportions of dogs were vaccinated in Venda Nova (4.35%), Noroeste (10.27%) and Barreiro (0.09%) districts, which according to that exhibited very

  18. Development of an autologous canine cancer vaccine system for resectable malignant tumors in dogs.

    PubMed

    Yannelli, J R; Wouda, R; Masterson, T J; Avdiushko, M G; Cohen, D A

    2016-12-01

    While conventional therapies exist for canine cancer, immunotherapies need to be further explored and applied to the canine setting. We have developed an autologous cancer vaccine (K9-ACV), which is available for all dogs with resectable disease. K9-ACV was evaluated for safety and immunogenicity for a variety of cancer types in a cohort of companion dogs under veterinary care. The autologous vaccine was prepared by enzymatic digestion of solid tumor biopsies. The resultant single cell suspensions were then UV-irradiated resulting in immunogenic cell death of the tumor cells. Following sterility and endotoxin testing, the tumor cells were admixed with CpG ODN adjuvant and shipped to the participating veterinary clinics. The treating veterinarians then vaccinated each patient with three intradermal injections (10 million cells per dose) at 30-day intervals (one prime and two boost injections). In a cohort of 20 dogs completing the study, 17 dogs (85%) developed an augmented IgG response to autologous tumor antigens as demonstrated using western blot analysis of pre- and post-peripheral blood samples. We also report several dogs have lived beyond expected survival time based on previously published data. In summary, K9-ACV is an additional option to be considered for the treatment of dogs with resectable cancer.

  19. Immunohistochemical detection of metalloproteinase-9 (MMP-9), anti-oxidant like 1 protein (AOP-1) and synaptosomal-associated protein (SNAP-25) in the cerebella of dogs naturally infected with spontaneous canine distemper.

    PubMed

    Bregano, Lívia C; Agostinho, Sabrina D; Roncatti, Flávio L B T; Pires, Marcília C; Riva, Henrique G; Luvizotto, Maria C R; Cardoso, Tereza C

    2011-01-01

    In most viral infections of the central nervous system (CNS), the integrity of brain extracelluar matrix (ECM), oxidative stress and dysfunction in neuronal transmission may contribute to the observed pathology. The purpose of this study was to investigate the role of these factors in demyelinating canine distemper virus (CDV) infections. Regardless of ECM integrity, the expression of metalloproteinase-9 (MMP-9) was visualized in microglial-like cells, whereas the expression of anti-oxidant like-1 (AOP-1) and synaptosomal associated protein (SNAP-25) was frequently detected in Purkinje cells (r(2) = 0.989; p < 0.05), regardless of whether the lesions were classified as acute or chronic. Increased numbers of immunolabeled microglia-like cells and reactive gliosis were observed in advanced cases of demyelinating CDV, suggesting that the expression of AOP-1 and SNAP-25 is correlated with the ultimate death of affected cells. Our findings bring a new perspective to understanding the role of the AOP-1, MMP-9 and SNAP-25 proteins in mediating chronic leukoencephalitis caused by CDV.

  20. Safety of administering the canine melanoma DNA vaccine (Oncept) to cats with malignant melanoma - a retrospective study.

    PubMed

    Sarbu, Luminita; Kitchell, Barbara E; Bergman, Philip J

    2017-02-01

    Objectives A xenogeneic human tyrosinase DNA vaccine was developed for treatment of dogs with oral malignant melanoma (Oncept; Merial). No studies have evaluated the safety or efficacy of this vaccine in cats. The purpose of this study was to evaluate the safety of the canine melanoma vaccine in cats diagnosed with melanoma. Methods Medical records were reviewed from cats diagnosed with malignant melanoma and treated with the canine melanoma DNA vaccine (Oncept). Data regarding signalment, melanoma location, treatments received, vaccine adverse effects and cause of death were collected. Results A total of 114 melanoma vaccines were administered to 24 cats. Seven cats (11.4%) had clinical adverse effects from a total of 13 vaccines classified as grade 1 or 2 based on the Veterinary Cooperative Oncology Group's common terminology criteria for adverse events v1.1. These included pain on vaccine administration, brief muscle fasciculation, transient inappetence, depression, nausea and mild increase in pigmentation at the injection site. Nineteen cats were deceased at study close. The most common cause of death was melanoma (14 cats). Hematological and biochemical changes were observed in six cats, five of which had concurrent disease or treatments that likely caused or greatly contributed to the laboratory abnormalities found. Therefore, these adverse events were considered unlikely to be caused by the melanoma vaccine. One cat had transient grade 1 hypoalbuminemia, which was possibly caused by the vaccination but not thoroughly evaluated. Conclusions and relevance The canine melanoma DNA vaccine can be safely administered to cats, with minimal risk of adverse effects.

  1. CHEMOKINE RECEPTOR 7 (CCR7)-EXPRESSION AND IFNγ PRODUCTION DEFINE VACCINE-SPECIFIC CANINE T CELL SUBSETS

    PubMed Central

    Hartley, Ashley N.; Tarleton, Rick L.

    2015-01-01

    Canines suffer from and serve as strong translational animals models for many immunological disorders and infectious diseases. Routine vaccination has been a mainstay of protecting dogs through the stimulation of robust antibody responses and expansion of memory T cell populations. Commercially available reagents and described techniques are limited for identifying and characterizing canine T cell subsets and evaluating T cell-specific effector function. To define reagents for delineating naïve versus activated T cells and identify antigen-specific T cells, we tested anti-human and anti-bovine T-cell specific cell surface marker reagents for cross-reactivity with canine peripheral blood mononuclear cells (PBMCs. Both CD4+ and CD8+ T cells from healthy canine donors showed reactivity to CCL19-Ig, a CCR7 ligand, and coexpression with CD62L. An in vitro stimulation with concanavalin A validated downregulation of CCR7 and CD62L expression on stimulated healthy control PBMCs, consistent with an activated T cell phenotype. Anti-IFNγ antibodies identified antigen-specific IFNγ-producing CD4+ and CD8+ T cells upon in vitro vaccine antigen PBMC stimulation. PBMC isolation within 24 hours of sample collection allowed for efficient cell recovery and accurate T cell effector function characterization. These data provide a reagent and techniques platform via flow cytometry for identifying canine T cell subsets and characterizing circulating antigen-specific canine T cells for potential use in diagnostic and field settings. PMID:25758065

  2. A live-attenuated influenza vaccine for H3N2 canine influenza virus.

    PubMed

    Rodriguez, Laura; Nogales, Aitor; Reilly, Emma C; Topham, David J; Murcia, Pablo R; Parrish, Colin R; Martinez Sobrido, Luis

    2017-04-01

    Canine influenza is a contagious respiratory disease in dogs caused by two subtypes (H3N2 and H3N8) of canine influenza virus (CIV). Currently, only inactivated influenza vaccines (IIVs) are available for the prevention of CIVs. Historically, live-attenuated influenza vaccines (LAIVs) have been shown to produce better immunogenicity and protection efficacy than IIVs. Here, we have engineered a CIV H3N2 LAIV by using the internal genes of a previously described CIV H3N8 LAIV as a master donor virus (MDV) and the surface HA and NA genes of a circulating CIV H3N2 strain. Our findings show that CIV H3N2 LAIV replicates efficiently at low temperature but its replication is impaired at higher temperatures. The CIV H3N2 LAIV was attenuated in vivo but induced better protection efficacy in mice against challenge with wild-type CIV H3N2 than a commercial CIV H3N2 IIV. This is the first description of a LAIV for the prevention of CIV H3N2 in dogs.

  3. Efficacy and safety of a live canine adenovirus-vectored rabies virus vaccine in swine.

    PubMed

    Liu, Ye; Zhang, Shoufeng; Ma, Guangpeng; Zhang, Fei; Hu, Rongliang

    2008-10-03

    Rabies infections in swine have been reported occasionally in recent years in certain geographic locations. Although a protective vaccine consisting of inactivated rabies virus is available for use in swine, searching for a more economically viable formulation for use in developing countries is always a priority. This work describes the testing of a canine adenovirus that expresses a rabies viral epitope (CAV-2-E3Delta-RGP) in a porcine rabies model. The data presented here show that the recombinant viral vaccine was effective in protecting swine against rabies if administered intramuscularly, but not orally or intranasally, and that protection was probably related to the development of a humoral response that lasted at least 28 weeks. Following vaccination, no behavioral abnormalities were observed in vaccinated swine and virus particles were not detected in either tissues or body fluids, indicating that this formulation was safe. The recombinant virus stimulated an effective level of antibody response in the immunized swine after a single intramuscular inoculation.

  4. Treatment of canine visceral leishmaniasis by the vaccine Leish-111f+MPL-SE.

    PubMed

    Trigo, Joelma; Abbehusen, Melissa; Netto, Eduardo M; Nakatani, Maria; Pedral-Sampaio, Geraldo; de Jesus, Robson Silva; Goto, Yasuyuki; Guderian, Jeffrey; Howard, Randall F; Reed, Steven G

    2010-04-26

    Immunotherapy of canine visceral leishmaniasis (CVL) may provide an alternative to both marginally effective chemotherapy and undesired euthanasia of infected dogs and could have a great impact not only on animal welfare, but also on control of human disease. Therefore, we examined the potential immunotherapeutic efficacy of the subunit vaccine Leish-111f+MPL-SE, which has undergone rigorous preclinical testing and been demonstrated safe in human clinical trials. Two separate trials were performed in Salvador, Brazil, to evaluate the vaccine for therapeutic efficacy against CVL caused by natural infection: an Open Trial and a Blinded Trial. In the Open Trial 59 dogs with clinically active CVL were sequentially allocated to four groups: group 1 received Leish-111f+MPL-SE; group 2 was treated with Glucantime; group 3 received a combination of the vaccine and Glucantime; and group 4 was given no treatment. At the 6-month assessment, the 13 non-treated dogs had either died or showed no clinical improvement. In contrast, most dogs in groups 1-3 showed initial improvement (100%, 80%, and 92%, respectively). Upon evaluation for a mean of 36 months after therapy, the following cure rates were observed: 75% for group 1 dogs (exact 95% confidence interval [CI] 43-95%), 64% for group 2 dogs (exact 95% CI 31-89%), and 50% for group 3 dogs (exact 95% CI 19-81%). Therapeutic efficacy of the Leish-111f+MPL-SE vaccine was reconfirmed in a subsequent Blinded Trial. The vaccine was effective for mild cases of CVL and was compromised in dogs with severe disease. Although further studies are required to understand mechanisms of action, the Leish-111f+MPL-SE vaccine is a promising tool to control VL in both dogs and humans.

  5. Immune Responses to rAAV6: The Influence of Canine Parvovirus Vaccination and Neonatal Administration of Viral Vector

    PubMed Central

    Arnett, Andrea L. H.; Garikipati, Dilip; Wang, Zejing; Tapscott, Stephen; Chamberlain, Jeffrey S.

    2011-01-01

    Recombinant adeno-associated viral (rAAV) vectors promote long-term gene transfer in many animal species. Significant effort has focused on the evaluation of rAAV delivery and the immune response in both murine and canine models of neuromuscular disease. However, canines provided for research purposes are routinely vaccinated against canine parvovirus (CPV). rAAV and CPV possess significant homology and are both parvoviruses. Thus, any immune response generated to CPV vaccination has the potential to cross-react with rAAV vectors. In this study, we investigated the immune response to rAAV6 delivery in a cohort of CPV-vaccinated canines and evaluated multiple vaccination regimens in a mouse model of CPV-vaccination. We show that CPV-vaccination stimulates production of neutralizing antibodies with minimal cross-reactivity to rAAV6. In addition, no significant differences were observed in the magnitude of the rAAV6-directed immune response between CPV-vaccinated animals and controls. Moreover, CPV-vaccination did not inhibit rAAV6-mediated transduction. We also evaluated the immune response to early rAAV6-vaccination in neonatal mice. The influence of maternal hormones and cytokines leads to a relatively permissive state in the neonate. We hypothesized that immaturity of the immune system would permit induction of tolerance to rAAV6 when delivered during the neonatal period. Mice were vaccinated with rAAV6 at 1 or 5 days of age, and subsequently challenged with rAAV6 exposure during adulthood via two sequential IM injections, 1 month apart. All vaccinated animals generated a significant neutralizing antibody response to rAAV6-vaccination that was enhanced following IM injection in adulthood. Taken together, these data demonstrate that the immune response raised against rAAV6 is distinct from that which is elicited by the standard parvoviral vaccines and is sufficient to prevent stable tolerization in neonatal mice. PMID:22065964

  6. Evaluation of a canine rabies vaccination campaign and characterization of owned-dog populations in the Philippines.

    PubMed

    Robinson, L E; Miranda, M E; Miranda, N L; Childs, J E

    1996-06-01

    A mass canine rabies vaccination campaign in Sorsogon Province, the Republic of the Philippines, was conducted in April and May 1993. From 1 to 14 days following visits by vaccination teams to 30 selected villages (barangays), survey teams revisited the barangays to assess vaccine coverage. Modified cluster survey methods were used to gather information about vaccine coverage in the owned-dog population (210 households) and about characteristics of owned-dogs and factors influencing owner willingness to participate in the campaign. Vaccinated dogs were identified by asking owners about receipt of certificates given by the vaccinating teams and examining each animal for a special collar or paint mark placed on the animal at the time of vaccination. Survey results indicated that 73% (178/243) of eligible dogs were vaccinated and 82% of vaccinated dogs were marked with a collar or paint. Dogs were owned by 69% of households and ranged in age from 3 days to 13 years (median = 1 year), and the ratio of male to females dogs was 1:1. The dog-to-human ratio was 1:3.8, with an average of 1.4 dogs per household or 2.1 dogs per dog-owning household. Most dogs were kept as guards (83%) and most were free-ranging (85%). The most common reasons dogs were not vaccinated included they could not be restrained (11/64), the owner was not home (10/64), and fear of injury resulting from vaccination (10/64). The owners of 20% of vaccinated dogs reported some adverse reaction in their pet. Improved vaccine coverage was significantly associated with restrained dogs kept primarily for guard functions by owners who received information about the vaccination campaign from multiple sources. Vaccine coverage was sufficiently high to potentially control rabies transmission among dogs through herd immunity and indicated a successful vaccine campaign.

  7. Cost-estimate and proposal for a development impact bond for canine rabies elimination by mass vaccination in Chad.

    PubMed

    Anyiam, Franziska; Lechenne, Monique; Mindekem, Rolande; Oussigéré, Assandi; Naissengar, Service; Alfaroukh, Idriss Oumar; Mbilo, Celine; Moto, Daugla Doumagoum; Coleman, Paul G; Probst-Hensch, Nicole; Zinsstag, Jakob

    2016-11-23

    Close to 69,000 humans die of rabies each year, most of them in Africa and Asia. Clinical rabies can be prevented by post-exposure prophylaxis (PEP). However, PEP is commonly not available or not affordable in developing countries. Another strategy besides treating exposed humans is the vaccination of vector species. In developing countries, the main vector is the domestic dog, that, once infected, is a serious threat to humans. After a successful mass vaccination of 70% of the dogs in N'Djaména, we report here a cost-estimate for a national rabies elimination campaign for Chad. In a cross-sectional survey in four rural zones, we established the canine : human ratio at the household level. Based on human census data and the prevailing socio-cultural composition of rural zones of Chad, the total canine population was estimated at 1,205,361 dogs (95% Confidence interval 1,128,008-1,736,774 dogs). Cost data were collected from government sources and the recent canine mass vaccination campaign in N'Djaména. A Monte Carlo simulation was used for the simulation of the average cost and its variability, using probability distributions for dog numbers and cost items. Assuming the vaccination of 100 dogs on average per vaccination post and a duration of one year, the total cost for the vaccination of the national Chadian canine population is estimated at 2,716,359 Euros (95% CI 2,417,353-3,035,081) for one vaccination round. A development impact bond (DIB) organizational structure and cash flow scenario were then developed for the elimination of canine rabies in Chad. Cumulative discounted cost of 28.3 million Euros over ten years would be shared between the government of Chad, private investors and institutional donors as outcome funders. In this way, the risk of the investment could be shared and the necessary investment could be made available upfront - a key element for the elimination of canine rabies in Chad.

  8. MT-PCR panel detection of canine parvovirus (CPV-2): Vaccine and wild-type CPV-2 can be difficult to differentiate in canine diagnostic fecal samples.

    PubMed

    Meggiolaro, Maira N; Ly, Anna; Rysnik-Steck, Benjamin; Silva, Carolina; Zhang, Joshua; Higgins, Damien P; Muscatello, Gary; Norris, Jacqueline M; Krockenberger, Mark; Šlapeta, Jan

    2017-03-01

    Canine parvovirus (CPV-2) remains an important cause of devastating enteritis in young dogs. It can be successfully prevented with live attenuated CPV-2 vaccines when given at the appropriate age and in the absence of maternal antibody interference. Rapid diagnosis of parvoviral enteritis in young dogs is essential to ensuring suitable barrier nursing protocols within veterinary hospitals. The current diagnostic trend is to use multiplexed PCR panels to detect an array of pathogens commonly responsible for diarrhea in dogs. The multiplexed PCR assays do not distinguish wild from vaccine CPV-2. They are highly sensitive and detect even a low level of virus shedding, such as those caused by the CPV-2 vaccine. The aim of this study was to identify the CPV-2 subtypes detected in diagnostic specimens and rule out occult shedding of CPV-2 vaccine strains. For a total of 21 samples that tested positive for CPV-2 in a small animal fecal pathogens diagnostic multiplexed tandem PCR (MT-PCR) panel during 2014-2016 we partially characterized the VP2 gene of CPV-2. Vaccine CPV-2 strain, wild type CPV-2a subtypes and vaccine-like CPV-2b subtypes were detected. High copy number was indicative of wild-type CPV-2a presence, but presence of vaccine-like CPV-2b had a variable copy number in fecal samples. A yardstick approach to a copy number or Ct-value to discriminate vaccine strain from a wild type virus of CPV-2 can be, in some cases, potentially misleading. Therefore, discriminating vaccine strain from a wild type subtype of CPV-2 remains ambitious.

  9. Virological and serological findings in dogs with naturally occurring distemper.

    PubMed

    Elia, Gabriella; Camero, Michele; Losurdo, Michele; Lucente, Maria Stella; Larocca, Vittorio; Martella, Vito; Decaro, Nicola; Buonavoglia, Canio

    2015-03-01

    Canine distemper virus (CDV) is the cause of a severe and highly contagious disease in dogs. The unpredictable and variable course of CDV-related disease may hamper correct diagnosis of infection and makes it crucial the collection of samples suitable for laboratory confirmation. In the present study we were able to follow the disease in two dogs infected naturally, collecting different biological matrices during the entire period of infection. By real time RT-PCR, viral RNA was detected and quantified, suggesting that urine and rectal swabs would be useful for ante-mortem diagnosis of distemper in dogs, regardless of the clinical stage and form of the illness.

  10. First peptide vaccine providing protection against viral infection in the target animal: studies of canine parvovirus in dogs.

    PubMed Central

    Langeveld, J P; Casal, J I; Osterhaus, A D; Cortés, E; de Swart, R; Vela, C; Dalsgaard, K; Puijk, W C; Schaaper, W M; Meloen, R H

    1994-01-01

    A synthetic peptide vaccine which protects dogs against challenge with virulent canine parvovirus is described. The amino acid sequence used was discovered in previous studies on the immunogenic properties of previously mapped antigenic sites and represents the amino-terminal region of viral protein VP2. As with marker vaccines, it is possible to discriminate between vaccinated dogs that have not been exposed to the virus and dogs that have been infected with the virus. The protective mechanism can be explained by a humoral response against the peptide aided by T-cell epitopes contained in the carrier protein used for peptide coupling. This is the first example of a synthetic peptide vaccine that induces protection in target animals. PMID:8207825

  11. Protection of dogs for 13 months against Bordetella bronchiseptica and canine parainfluenza virus with a modified live vaccine.

    PubMed

    Jacobs, A A C; Theelen, R P H; Jaspers, R; Horspool, L J I; Sutton, D; Bergman, J G H E; Paul, G

    2005-07-02

    Twelve specific pathogen-free (spf) puppies were vaccinated intranasally with a bivalent, modified live vaccine against infectious tracheobronchitis (group 1) and six puppies of the same age and from the same source served as unvaccinated controls (group 2). Both groups were challenged with wild-type Bordetella bronchiseptica and canine parainfluenza virus by the aerosol route 56 weeks after group 1 had been vaccinated, and at the same time six 10-week-old spf puppies from the same source (group 3) were also challenged. Oronasal swabs were taken regularly before and after the challenge, for the isolation of bacteria and viruses, and the dogs were observed for clinical signs for three weeks after the challenge. The control dogs became culture-positive for B bronchiseptica and canine parainfluenza virus, but the isolation yields from the vaccinated group were significantly lower (P<0.05). The mean clinical scores of the vaccinated group were 61 per cent lower than the scores of group 2 (P=0.009), and 90 per cent lower than the scores of group 3 (P=0.001).

  12. Clinicopathological findings in dogs with distemper encephalomyelitis presented without characteristic signs of the disease.

    PubMed

    Amude, A M; Alfieri, A A; Alfieri, A F

    2007-06-01

    The clinical diagnosis of distemper is difficult in dogs presented with nervous deficits in the absence of extraneural signs and myoclonus. The aim of this study is to verify how the clinicopathological findings may suggest distemper encephalomyelitis in such cases. We prospectively investigated 20 necropsied dogs presented with neurological signs without those characteristic signs of distemper at the time of hospital admission. Eight out of 20 dogs were diagnosed with distemper encephalomyelitis at post mortem by reverse transcription-polymerase chain reaction (RT-PCR) and histological examination. Cerebellar and/or vestibular signs progressing to tetraparesis/plegia were frequent neurological signs. Abnormalities in hematologic findings were non-specific, nevertheless the cerebrospinal fluid evaluation could suggest canine distemper virus (CDV) infection by a lymphocytic pleocytosis. At post mortem chronic CDV encephalomyelitis was predominant. Our clinical results, as well as the predominance of chronic encephalomyelitis, differ from other studies about CDV encephalomyelitis with naturally infected dogs presenting extraneural signs and myoclonus.

  13. Gentamicin-Attenuated Leishmania infantum Vaccine: Protection of Dogs against Canine Visceral Leishmaniosis in Endemic Area of Southeast of Iran

    PubMed Central

    Daneshvar, Hamid; Namazi, Mohammad Javad; Kamiabi, Hossein; Burchmore, Richard; Cleaveland, Sarah; Phillips, Stephen

    2014-01-01

    An attenuated line of Leishmania infantum (L. infantum H-line) has been established by culturing promastigotes in vitro under gentamicin pressure. A vaccine trial was conducted using 103 naive dogs from a leishmaniosis non-endemic area (55 vaccinated and 48 unvaccinated) brought into an endemic area of southeast Iran. No local and/or general indications of disease were observed in the vaccinated dogs immediately after vaccination. The efficacy of the vaccine was evaluated after 24 months (4 sandfly transmission seasons) by serological, parasitological analyses and clinical examination. In western blot analysis of antibodies to L. infantum antigens, sera from 10 out of 31 (32.2%) unvaccinated dogs, but none of the sera from vaccinated dogs which were seropositive at >100, recognized the 21 kDa antigen of L. infantum wild-type (WT). Nine out of 31 (29%) unvaccinated dogs, but none of vaccinated dogs, were positive for the presence of Leishmania DNA. One out of 46 (2.2%) vaccinated dogs and 9 out of 31 (29%) unvaccinated dogs developed clinical signs of disease. These results suggest that gentamicin-attenuated L. infantum induced a significant and strong protective effect against canine visceral leishmaniosis in the endemic area. PMID:24743691

  14. The failure of an inactivated mink enteritis virus vaccine in four preparations to provide protection to dogs against challenge with canine parvovirus-2.

    PubMed Central

    Carman, S; Povey, C

    1982-01-01

    Four experimental vaccine preparations comprising a strain of mink enteritis virus inactivated by either formalin or beta-propiolactone, and either adjuvanted or nonadjuvanted, failed to stimulate a consistent serum antibody response in 20 vaccinated dogs and failed to protect all but one of these dogs against oral challenge with canine parvovirus-2. PMID:6280820

  15. Cytokine-enhanced vaccine and suicide gene therapy as surgery adjuvant treatments for spontaneous canine melanoma.

    PubMed

    Finocchiaro, L M E; Glikin, G C

    2008-02-01

    We evaluated the safety, efficacy and anti-tumor effects of a surgery adjuvant treatment on canine patients with malignant melanoma. This approach combined suicide gene therapy with a subcutaneous vaccine composed by formolized tumor cells and irradiated xenogeneic cells producing human interleukin-2 and granulocyte-macrophage colony-stimulating factor. The post-surgical margin of the cavity was infiltrated with lipid-complexed thymidine kinase suicide gene coadministrated with ganciclovir. Toxicity was minimal or absent in all patients. With respect to surgery-treated controls (SC), this combined treatment (CT) significantly increased the fraction of patients local disease-free from 6 to 58% and distant metastases-free from 43 to 78% (Fisher's Exact test). In addition, CT significantly improved both SC overall 78 (23-540) and metastasis-free survival 112 (0-467) days to more than 1312 days (respective ranges: 43-1312 and 0-1312) (Kaplan-Meier analysis). In those patients subjected to partial surgery or presenting local recurrence, the efficacy of CT was verified by a 49% of objective responses that averaged 85% of tumor mass loss, while 22% displayed tumor progression as 94% of SC did. Therefore, surgery adjuvant CT controlled tumor growth, delaying or preventing post-surgical recurrence and distant metastasis, significantly extending survival and recovering the quality of life.

  16. Development of a novel vaccine against canine parvovirus infection with a clinical isolate of the type 2b strain

    PubMed Central

    Park, Seon Ah; Park, Seung-Yong; Song, Chang-Seon; Choi, In-Soo; Kim, Hwi Yool; Lee, Joong-Bok

    2012-01-01

    Purpose In spite of an extensive vaccination program, parvoviral infections still pose a major threat to the health of dogs. Materials and Methods We isolated a novel canine parvovirus (CPV) strain from a dog with enteritis. Nucleotide and amino acid sequence analysis of the isolate showed that it is a novel type 2b CPV with asparagine at the 426th position and valine at the 555th position in VP2. To develop a vaccine against CPV infection, we passaged the isolate 4 times in A72 cells. Results The attenuated isolate conferred complete protection against lethal homologous CPV infection in dogs such that they did not develop any clinical symptoms, and their antibody titers against CPV were significantly high at 7-11 days post infection. Conclusion These results suggest that the virus isolate obtained after passaging can be developed as a novel vaccine against paroviral infection. PMID:23596579

  17. Vaccination of dogs with Duramune DAPPi+LC protects against pathogenic canine parvovirus type 2c challenge.

    PubMed

    Wilson, S; Stirling, C; Borowski, S; Thomas, A; King, V; Salt, J

    2013-06-22

    In this study, we determined whether vaccination with Duramune DAPPi+LC containing canine parvovirus (CPV) type 2b protects against challenge with virulent CPV antigenic type 2c. Seven healthy dogs, seronegative for CPV2, were enrolled into two treatment groups; five were vaccinated twice, 21 days apart, with minimum titre vaccine, and two were given saline. Dogs were challenged with CPV 2c three weeks later. Clinical observations, body weight and rectal temperature measurements, blood samples for serology and white blood cell counts and faecal samples for virus excretion were collected. Control dogs remained seronegative until challenge; vaccinated dogs seroconverted and were positive for antibodies to CPV2 from day 21. Four days after challenge, clinical signs associated with parvovirus infection (vomiting, paroxysmal shivering, depression, loose stools) were observed in the control dogs. Both animals were withdrawn from the study for welfare reasons one day later. On day 47, leucopenia was observed in controls, with white blood cell counts less than 50 per cent prechallenge values. No specific clinical sign of parvovirus infection were observed in the vaccinated dogs, nor was (detectable) challenge virus shed in faeces suggesting that antibodies generated contributed sterilising immunity. We conclude that vaccination of dogs with Duramune DAPPi+LC protects against challenge with a virulent field strain of CPV 2c.

  18. Advances in flow cytometric serology for canine visceral leishmaniasis: diagnostic applications when distinct clinical forms, vaccination and other canine pathogens become a challenge.

    PubMed

    Andrade, Renata Aline; Silva Araújo, Márcio Sobreira; Reis, Alexandre Barbosa; Gontijo, Célia Maria Ferreira; Vianna, Leonardo Rocha; Mayrink, Wilson; Martins-Filho, Olindo Assis

    2009-03-15

    We have previously reported the applicability of flow cytometry anti-fixed Leishmania infantum chagasi promastigotes IgG (FC-AFPA-IgG) as a novel serological device for laboratorial diagnosis of CVL. Herein, we validate throughout a blind study applied into a broader range of coded sera samples that FC-AFPA-IgG at serum dilution 1:8192 have an outstanding performance to discriminate the serological reactivity of canine visceral leishmaniasis (CVL, n=64) and Leishmune vaccines (VAC, n=62) and non-infected controls (NI, n=25). Moreover, we have evaluated the performance of indirect immunofluorescence antibody test (IFAT) and the crude-antigen enzyme-linked immunosorbent assay (ELISA) in parallel with FC-AFPA-IgG, to discriminate the seroreactivity of NI, CVL and VAC. Our data demonstrated that both ELISA and FC-AFPA-IgG showed similar performance to detect the seronegativity in 100% of NI, whereas FC-AFPA-IgG displayed better performance to exclude seropositivity in 100% of VAC. The high kappa agreement indexes observed suggested similar performance between these two serological testes when distinct clinical forms of CVL become a challenge. Furthermore, the FC-AFPA-IgG applied at sera dilution 1:8192 showed a remarkable performance to discriminate CVL from other co-endemic canine infections with high co-negativity in dogs infected with Trypanosoma cruzi and Leishmania braziliensis (86% and 84%, respectively). In conclusion, the data presented here re-emphasize the applicability of FC-AFPA-IgG as an innovative methodology able to discriminate post-infection imunomediated seroreactivity from that triggered by prophylactic immunization with minor cross-reactivity with other relevant canine pathogens, which may contribute as a supplementary assay for the CVL immunodiagnosis.

  19. Distemper: not a new disease in lions and tigers.

    PubMed

    Myers, D L; Zurbriggen, A; Lutz, H; Pospischil, A

    1997-03-01

    In light of recent canine distemper virus (CDV) epidemics, we set out to determine the historical significance of CDV infection in captive lions and tigers in Switzerland. The retrospective case material consisted of 42 lion and tiger necropsy cases from 1972 to 1992. Necropsy reports for all lions and tigers were reviewed. All existing paraffin tissues were immunohistochemically examined with a polyclonal antibody raised against CDV. The results for 19 of the 42 lions and tigers were classified as positive by immunohistochemistry; 23 results were negative or questionable. The results for four animals (three positive and one negative ) were further tested by in situ hybridization, and the results concurred with the immunohistochemistry findings. CDV infection of large cats is older and more widespread than previously thought. All large cats in captivity should be immunized even if canine distemper is not believed to be a problem for large cats in the area.

  20. Distemper: not a new disease in lions and tigers.

    PubMed Central

    Myers, D L; Zurbriggen, A; Lutz, H; Pospischil, A

    1997-01-01

    In light of recent canine distemper virus (CDV) epidemics, we set out to determine the historical significance of CDV infection in captive lions and tigers in Switzerland. The retrospective case material consisted of 42 lion and tiger necropsy cases from 1972 to 1992. Necropsy reports for all lions and tigers were reviewed. All existing paraffin tissues were immunohistochemically examined with a polyclonal antibody raised against CDV. The results for 19 of the 42 lions and tigers were classified as positive by immunohistochemistry; 23 results were negative or questionable. The results for four animals (three positive and one negative ) were further tested by in situ hybridization, and the results concurred with the immunohistochemistry findings. CDV infection of large cats is older and more widespread than previously thought. All large cats in captivity should be immunized even if canine distemper is not believed to be a problem for large cats in the area. PMID:9067652

  1. Rationale and support for a One Health program for canine vaccination as the most cost-effective means of controlling zoonotic rabies in endemic settings.

    PubMed

    Lavan, Robert P; King, Alasdair I MacG; Sutton, David J; Tunceli, Kaan

    2017-03-23

    Although dog vaccination has been demonstrated to reduce and eliminate rabies in humans, during meetings there are often calls for further pilot studies. The assembled data proves that a widespread approach is now required. While zoonotic rabies has a minimal presence in developed nations, it is endemic throughout most of Asia and Africa, where it is considered to be a neglected tropical disease. In these areas, rabies causes an estimated annual mortality of at least 55,000 human deaths. Worldwide rabid dogs are the source of the vast majority of human rabies exposures. The World Health Organization (WHO), the Food and Agriculture Organization (FAO) of the United Nations and the World Organization for Animal Health (OIE) advocate a collaborative One Health approach involving human public health and veterinary agencies, with mass canine vaccination programs in endemic areas being the mainstay of strategies to eliminate dog-mediated human rabies. While post-exposure prophylaxis (PEP) is effective in preventing deaths in people exposed to rabies, it is comparatively expensive and has little impact on the canine reservoir that is the primary source of zoonotic rabies. Indiscriminate culling of the dog population is expensive and there is little evidence that it is effective in controlling rabies in non-island locations. Mass canine vaccination programs using a One Health framework that achieves a minimum 70% vaccination coverage during annual campaigns have proven to be cost-effective in controlling zoonotic rabies in endemic, resource-poor regions. Case studies, such as in Tanzania and Bhutan, illustrate how an approach based on mass canine rabies vaccination has effectively reduced both canine and human rabies to minimal levels. The multiple benefits of mass canine rabies vaccination in these cases included eliminating rabies in the domestic dog reservoirs, eliminating human rabies cases, and decreasing the rabies economic burden by reducing expenditures on PEP.

  2. Distemper Outbreak and Its Effect on African Wild Dog Conservation

    PubMed Central

    van de Bildt, Marco W.G.; Kuiken, Thijs; Visee, Aart M.; Lema, Sangito; Fitzjohn, Tony R.

    2002-01-01

    In December 2000, an infectious disease spread through a captive breeding group of African wild dogs (Lycaon pictus) in Tanzania, killing 49 of 52 animals within 2 months. The causative agent was identified as Canine distemper virus (CDV) by means of histologic examination, virus isolation, reverse transcriptase-polymerase chain reaction analysis, and nucleotide sequencing. This report emphasizes the importance of adequate protection against infectious diseases for the successful outcome of captive breeding programs of endangered species. PMID:11897078

  3. Oral vaccination of dogs (Canis familiaris) with baits containing the recombinant rabies-canine adenovirus type-2 vaccine confers long-lasting immunity against rabies.

    PubMed

    Zhang, Shoufeng; Liu, Ye; Fooks, Anthony R; Zhang, Fei; Hu, Rongliang

    2008-01-17

    Rabies is a reemerging and fatal infectious disease in Asia mainly caused by exposure to rabid dogs. Prevention of dog rabies would be the most effective way to stop rabies transmission to humans. However, vaccinating stray dogs in urban and rural areas using conventional vaccines is always difficult and is not cost-effective for use in most areas including China. Further to previous studies from our laboratory, we developed a bait containing the recombinant rabies vaccine and performed a non-parenteral trial in dogs. This vaccine was intranasally administrated once to 46 dogs in solution form with 1 x 10(8.5) PFU and orally to 90 dogs in specially designed baits with 3 x 10(8.5) PFU of the recombinant canine adenovirus. Results showed that about 87.5% (119/136) of the immunized dogs developed virus neutralizing antibodies (VNA). The immune response against rabies in dogs was detectable at 2-3 weeks after administration, reaching a peak by 5-6 weeks. Among the seroconverted animals, 90.8% (108/119) elicited a VNA response for over 24 months. The antibody titer during the 2 years was above 0.5IU /ml while showing a gradual but slow decline from the 6th week after vaccination. In a challenge experiment of 10 dogs with 60,000 mouse LD(50) of CVS-24 2 years after the vaccination, all the dogs survived. This demonstrated that the recombinant vaccine could be orally administrated and the bait was effective for the oral vaccination of dogs.

  4. Impact of LbSapSal Vaccine in Canine Immunological and Parasitological Features before and after Leishmania chagasi-Challenge

    PubMed Central

    Resende, Lucilene Aparecida; Aguiar-Soares, Rodrigo Dian de Oliveira; Gama-Ker, Henrique; Roatt, Bruno Mendes; de Mendonça, Ludmila Zanandreis; Alves, Marina Luiza Rodrigues; da Silveira-Lemos, Denise; Corrêa-Oliveira, Rodrigo; Martins-Filho, Olindo Assis; Araújo, Márcio Sobreira Silva; Fujiwara, Ricardo Toshio; Gontijo, Nelder Figueiredo; Reis, Alexandre Barbosa; Giunchetti, Rodolfo Cordeiro

    2016-01-01

    Dogs represent the most important domestic reservoir of L. chagasi (syn. L. infantum). A vaccine against canine visceral leishmaniasis (CVL) would be an important tool for decreasing the anxiety related to possible L. chagasi infection and for controlling human visceral leishmaniasis (VL). Because the sand fly salivary proteins are potent immunogens obligatorily co-deposited during transmission of Leishmania parasites, their inclusion in an anti-Leishmania vaccine has been investigated in past decades. We investigated the immunogenicity of the “LbSapSal” vaccine (L. braziliensis antigens, saponin as adjuvant, and Lutzomyia longipalpis salivary gland extract) in dogs at baseline (T0), during the post-vaccination protocol (T3rd) and after early (T90) and late (T885) times following L. chagasi-challenge. Our major data indicated that immunization with “LbSapSal” is able to induce biomarkers characterized by enhanced amounts of type I (tumor necrosis factor [TNF]-α, interleukin [IL]-12, interferon [IFN]-γ) cytokines and reduction in type II cytokines (IL-4 and TGF-β), even after experimental challenge. The establishment of a prominent pro-inflammatory immune response after “LbSapSal” immunization supported the increased levels of nitric oxide production, favoring a reduction in spleen parasitism (78.9%) and indicating long-lasting protection against L. chagasi infection. In conclusion, these results confirmed the hypothesis that the “LbSapSal” vaccination is a potential tool to control the Leishmania chagasi infection. PMID:27556586

  5. Impact of LbSapSal Vaccine in Canine Immunological and Parasitological Features before and after Leishmania chagasi-Challenge.

    PubMed

    Resende, Lucilene Aparecida; Aguiar-Soares, Rodrigo Dian de Oliveira; Gama-Ker, Henrique; Roatt, Bruno Mendes; Mendonça, Ludmila Zanandreis de; Alves, Marina Luiza Rodrigues; Silveira-Lemos, Denise da; Corrêa-Oliveira, Rodrigo; Martins-Filho, Olindo Assis; Araújo, Márcio Sobreira Silva; Fujiwara, Ricardo Toshio; Gontijo, Nelder Figueiredo; Reis, Alexandre Barbosa; Giunchetti, Rodolfo Cordeiro

    2016-01-01

    Dogs represent the most important domestic reservoir of L. chagasi (syn. L. infantum). A vaccine against canine visceral leishmaniasis (CVL) would be an important tool for decreasing the anxiety related to possible L. chagasi infection and for controlling human visceral leishmaniasis (VL). Because the sand fly salivary proteins are potent immunogens obligatorily co-deposited during transmission of Leishmania parasites, their inclusion in an anti-Leishmania vaccine has been investigated in past decades. We investigated the immunogenicity of the "LbSapSal" vaccine (L. braziliensis antigens, saponin as adjuvant, and Lutzomyia longipalpis salivary gland extract) in dogs at baseline (T0), during the post-vaccination protocol (T3rd) and after early (T90) and late (T885) times following L. chagasi-challenge. Our major data indicated that immunization with "LbSapSal" is able to induce biomarkers characterized by enhanced amounts of type I (tumor necrosis factor [TNF]-α, interleukin [IL]-12, interferon [IFN]-γ) cytokines and reduction in type II cytokines (IL-4 and TGF-β), even after experimental challenge. The establishment of a prominent pro-inflammatory immune response after "LbSapSal" immunization supported the increased levels of nitric oxide production, favoring a reduction in spleen parasitism (78.9%) and indicating long-lasting protection against L. chagasi infection. In conclusion, these results confirmed the hypothesis that the "LbSapSal" vaccination is a potential tool to control the Leishmania chagasi infection.

  6. Whole genome sequence analysis of the arctic-lineage strain responsible for distemper in Italian wolves and dogs through a fast and robust next generation sequencing protocol.

    PubMed

    Marcacci, Maurilia; Ancora, Massimo; Mangone, Iolanda; Teodori, Liana; Di Sabatino, Daria; De Massis, Fabrizio; Camma', Cesare; Savini, Giovanni; Lorusso, Alessio

    2014-06-01

    Dynamic surveillance and characterization of canine distemper virus (CDV) circulating strains are essential against possible vaccine breakthroughs events. This study describes the setup of a fast and robust next-generation sequencing (NGS) Ion PGM™ protocol that was used to obtain the complete genome sequence of a CDV isolate (CDV2784/2013). CDV2784/2013 is the prototype of CDV strains responsible for severe clinical distemper in dogs and wolves in Italy during 2013. CDV2784/2013 was isolated on cell culture and total RNA was used for NGS sample preparation. A total of 112.3 Mb of reads were assembled de novo using MIRA version 4.0rc4, which yielded a total number of 403 contigs with 12.1% coverage. The whole genome (15,690 bp) was recovered successfully and compared to those of existing CDV whole genomes. CDV2784/2013 was shown to have 92% nt identity with the Onderstepoort vaccine strain. This study describes for the first time a fast and robust Ion PGM™ platform-based whole genome amplification protocol for non-segmented negative stranded RNA viruses starting from total cell-purified RNA. Additionally, this is the first study reporting the whole genome analysis of an Arctic lineage strain that is known to circulate widely in Europe, Asia and USA.

  7. Cytokine-Enhanced Vaccine and Interferon-β plus Suicide Gene Therapy as Surgery Adjuvant Treatments for Spontaneous Canine Melanoma

    PubMed Central

    Fondello, Chiara; Gil-Cardeza, María L.; Rossi, Úrsula A.; Villaverde, Marcela S.; Riveros, María D.; Glikin, Gerardo C.

    2015-01-01

    Abstract We present here a nonviral immunogene therapy trial for canine malignant melanoma, an aggressive disease displaying significant clinical and histopathological overlapping with human melanoma. As a surgery adjuvant approach, it comprised the co-injection of lipoplexes bearing herpes simplex virus thymidine kinase and canine interferon-β genes at the time of surgery, combined with the periodic administration of a subcutaneous genetic vaccine composed of tumor extracts and lipoplexes carrying the genes of human interleukin-2 and human granulocyte-macrophage colony-stimulating factor. Following complete surgery (CS), the combined treatment (CT) significantly raised the portion of local disease-free canine patients from 11% to 83% and distant metastases-free (M0) from 44% to 89%, as compared with surgery-only-treated controls (ST). Even after partial surgery (PS), CT better controlled the systemic disease (M0: 82%) than ST (M0: 48%). Moreover, compared with ST, CT caused a significant 7-fold (CS) and 4-fold (PS) rise of overall survival, and >17-fold (CS) and >13-fold (PS) rise of metastasis-free survival. The dramatic increase of PS metastasis-free survival (>1321 days) and CS recurrence- and metastasis-free survival (both >2251 days) demonstrated that CT was shifting a rapidly lethal disease into a chronic one. In conclusion, this surgery adjuvant CT was able of significantly delaying or preventing postsurgical recurrence and distant metastasis, increasing disease-free and overall survival, and maintaining the quality of life. The high number of canine patients involved in CT (301) and the extensive follow-up (>6 years) with minimal or absent toxicity warrant the long-term safety and efficacy of this treatment. This successful clinical outcome justifies attempting a similar scheme for human melanoma. PMID:25762364

  8. Cytokine-Enhanced Vaccine and Interferon-β plus Suicide Gene Therapy as Surgery Adjuvant Treatments for Spontaneous Canine Melanoma.

    PubMed

    Finocchiaro, Liliana M E; Fondello, Chiara; Gil-Cardeza, María L; Rossi, Úrsula A; Villaverde, Marcela S; Riveros, María D; Glikin, Gerardo C

    2015-06-01

    We present here a nonviral immunogene therapy trial for canine malignant melanoma, an aggressive disease displaying significant clinical and histopathological overlapping with human melanoma. As a surgery adjuvant approach, it comprised the co-injection of lipoplexes bearing herpes simplex virus thymidine kinase and canine interferon-β genes at the time of surgery, combined with the periodic administration of a subcutaneous genetic vaccine composed of tumor extracts and lipoplexes carrying the genes of human interleukin-2 and human granulocyte-macrophage colony-stimulating factor. Following complete surgery (CS), the combined treatment (CT) significantly raised the portion of local disease-free canine patients from 11% to 83% and distant metastases-free (M0) from 44% to 89%, as compared with surgery-only-treated controls (ST). Even after partial surgery (PS), CT better controlled the systemic disease (M0: 82%) than ST (M0: 48%). Moreover, compared with ST, CT caused a significant 7-fold (CS) and 4-fold (PS) rise of overall survival, and >17-fold (CS) and >13-fold (PS) rise of metastasis-free survival. The dramatic increase of PS metastasis-free survival (>1321 days) and CS recurrence- and metastasis-free survival (both >2251 days) demonstrated that CT was shifting a rapidly lethal disease into a chronic one. In conclusion, this surgery adjuvant CT was able of significantly delaying or preventing postsurgical recurrence and distant metastasis, increasing disease-free and overall survival, and maintaining the quality of life. The high number of canine patients involved in CT (301) and the extensive follow-up (>6 years) with minimal or absent toxicity warrant the long-term safety and efficacy of this treatment. This successful clinical outcome justifies attempting a similar scheme for human melanoma.

  9. Canine Parvovirus (CPV) Vaccination: Comparison of Neutralizing Antibody Responses in Pups after Inoculation with CPV2 or CPV2b Modified Live Virus Vaccine

    PubMed Central

    Pratelli, Annamaria; Cavalli, Alessandra; Martella, Vito; Tempesta, Maria; Decaro, Nicola; Carmichael, Leland Eugene; Buonavoglia, Canio

    2001-01-01

    Canine parvovirus type 2 (CPV2) emerged in 1978 as causative agent of a new disease of dogs. New antigenic variants (biotypes), designated CPV2a and CPV2b, became widespread during 1979 to 1980 and 1984, respectively. At the present time the original CPV2 has disappeared in the dog population and has been replaced by the two new viruses. In the present study the comparison of neutralizing antibody titers in two groups of pups (18 pups in each group) inoculated with CPV2 and CPV2b modified live virus vaccines is reported. Using the hemagglutination inhibition (HI) test, relevant differences between antibody titers, against either the homologous or the heterologous virus, were not constantly observed. Using the neutralization (Nt) test, however, the pups inoculated with CPV2 had antibody titers which were approximately 30 times higher to the homologous virus (mean, 4,732) than to the heterologous virus (CPV2b) (mean, 162). The results of these experiments support two conclusions: (i) the HI test may not always accurately evaluate the true immune status of dogs with respect to CPV, and (ii) dogs inoculated with CPV2 vaccine develop relatively low Nt antibody titers against the heterologous virus (CPV2b). These data may suggest an advantage for new vaccines, considering that most presently licensed vaccines are produced with CPV2, which no longer exists in the dog population. PMID:11329467

  10. Canine adenovirus type 1 in a fennec fox (Vulpes zerda).

    PubMed

    Choi, Jeong-Won; Lee, Hyun-Kyoung; Kim, Seong-Hee; Kim, Yeon-Hee; Lee, Kyoung-Ki; Lee, Myoung-Heon; Oem, Jae-Ku

    2014-12-01

    A 10-mo-old female fennec fox (Vulpes zerda) with drooling suddenly died and was examined postmortem. Histologic examination of different tissue samples was performed. Vacuolar degeneration and diffuse fatty change were observed in the liver. Several diagnostic methods were used to screen for canine parvovirus, canine distemper virus, canine influenza virus, canine coronavirus, canine parainfluenza virus, and canine adenovirus (CAdV). Only CAdV type 1 (CAdV-1) was detected in several organs (liver, lung, brain, kidney, spleen, and heart), and other viruses were not found. CAdV-1 was confirmed by virus isolation and nucleotide sequencing.

  11. Vaccination with a preparation based on recombinant cysteine peptidases and canine IL-12 does not protect dogs from infection with Leishmania infantum.

    PubMed

    Poot, J; Spreeuwenberg, K; Sanderson, S J; Schijns, V E C J; Mottram, J C; Coombs, G H; Vermeulen, A N

    2006-03-24

    Cysteine peptidases (CPs) have been implicated in various processes central to the pathogenicity of Leishmania parasites, and are thought to be key factors in the host-parasite interaction. In order to fully evaluate the potential of the CPs as vaccine candidates, studies in natural host species are required. In the study we report here, recombinant L. infantum CPs CPA and CPB were used to vaccinate dogs. In order to induce an appropriate response against the antigens, recombinant canine IL-12 was added as an adjuvant either by itself or in combination with Quil A. After vaccination, dogs were given an intravenous challenge with promastigotes of L. infantum JPC strain. In both vaccinated groups (CPs with IL-12 or CPs with IL-12 and Quil A) CP-specific antibodies were detected after vaccination, indicating that there was a reaction to the vaccine. However, all dogs were found parasite-positive and all developed some degree of clinical leishmaniosis. The observed lack of efficacy of the candidate vaccines could be due, completely or in part, to a number of factors associated with the vaccine antigen, the adjuvant or host-parasite interactions. When compared to results from other studies, it seems less likely that the molecular conformation of the rCPs or rIL-12 caused this lack of efficacy. More plausible explanations are the dose and timing of the IL-12 application and the potentially different effects IL-12 induces as an adjuvant in either the murine or the canine leishmaniosis model.

  12. Porcupine quills in raccoons as an indicator of rabies, distemper, or both diseases: disease management implications.

    PubMed

    Rosatte, Rick; Wandeler, Alex; Muldoon, Frances; Campbell, Doug

    2007-03-01

    A relationship was detected between the presence of embedded porcupine quills and the diagnosis of rabies in raccoons in eastern Canada during 1999-2004. No relationship was found between the presence of quills in raccoons and the diagnosis of canine distemper. Raccoons with embedded quills should be submitted for rabies testing.

  13. The detection and differentiation of canine respiratory pathogens using oligonucleotide microarrays.

    PubMed

    Wang, Lih-Chiann; Kuo, Ya-Ting; Chueh, Ling-Ling; Huang, Dean; Lin, Jiunn-Horng

    2017-05-01

    Canine respiratory diseases are commonly seen in dogs along with co-infections with multiple respiratory pathogens, including viruses and bacteria. Virus infections in even vaccinated dogs were also reported. The clinical signs caused by different respiratory etiological agents are similar, which makes differential diagnosis imperative. An oligonucleotide microarray system was developed in this study. The wild type and vaccine strains of canine distemper virus (CDV), influenza virus, canine herpesvirus (CHV), Bordetella bronchiseptica and Mycoplasma cynos were detected and differentiated simultaneously on a microarray chip. The detection limit is 10, 10, 100, 50 and 50 copy numbers for CDV, influenza virus, CHV, B. bronchiseptica and M. cynos, respectively. The clinical test results of nasal swab samples showed that the microarray had remarkably better efficacy than the multiplex PCR-agarose gel method. The positive detection rate of microarray and agarose gel was 59.0% (n=33) and 41.1% (n=23) among the 56 samples, respectively. CDV vaccine strain and pathogen co-infections were further demonstrated by the microarray but not by the multiplex PCR-agarose gel. The oligonucleotide microarray provides a highly efficient diagnosis alternative that could be applied to clinical usage, greatly assisting in disease therapy and control.

  14. Safety and Efficacy of a Genetic Vaccine Targeting Telomerase Plus Chemotherapy for the Therapy of Canine B-Cell Lymphoma

    PubMed Central

    Gavazza, Alessandra; Lubas, George; Fridman, Arthur; Peruzzi, Daniela; Impellizeri, Joseph A.; Luberto, Laura; Marra, Emanuele; Roscilli, Giuseppe; Ciliberto, Gennaro

    2013-01-01

    Abstract Client-owned pet dogs represent exceptional translational models for advancement of cancer research because they reflect the complex heterogeneity observed in human cancer. We have recently shown that a genetic vaccine targeting dog telomerase reverse transcriptase (dTERT) and based on adenovirus DNA electro-gene-transfer (Ad/DNA-EGT) technology can induce strong cell-mediated immune responses against this tumor antigen and increase overall survival of dogs affected by B-cell lymphosarcoma (LSA) in comparison with historical controls when combined with a cyclophosphamide, vincristine, and prednisone (COP) chemotherapy regimen. Here, we have conducted a double-arm clinical trial with an extended number of LSA patients, measured the antigen-specific immune response, and evaluated potential toxic effects of the immunotherapy along with a follow-up of patients survival for 3.5 years. The immune response was measured by enzyme-linked immunospot assay. The expression of dTERT was quantified by quantitative polymerase chain reaction. Changes in hematological parameters, local/systemic toxicity or organic dysfunction and fever were monitored over time during the treatment. dTERT-specific cell-mediated immune responses were induced in almost all treated animals. No adverse effects were observed in any dog patient that underwent treatment. The overall survival time of vaccine/COP-treated dogs was significantly increased over the COP-only cohort (>76.1 vs. 29.3 weeks, respectively, p<0.0001). There was a significant association between dTERT expression levels in LSA cells and overall survival among vaccinated patients. In conclusion, Ad/DNA-EGT-based cancer vaccine against dTERT in combination with COP chemotherapy is safe and significantly prolongs the survival of LSA canine patients. These data confirm the therapeutic efficacy of dTERT vaccine and support the evaluation of this approach for other cancer types as well as the translation of this approach to human

  15. Induction of neutralizing antibodies by a tobacco chloroplast-derived vaccine based on a B cell epitope from canine parvovirus

    SciTech Connect

    Molina, Andrea; Veramendi, Jon . E-mail: jon@unavarra.es; Hervas-Stubbs, Sandra

    2005-11-25

    The 2L21 epitope of the VP2 protein from the canine parvovirus (CPV), fused to the cholera toxin B subunit (CTB-2L21), was expressed in transgenic tobacco chloroplasts. Mice and rabbits that received protein-enriched leaf extracts by parenteral route produced high titers of anti-2L21 antibodies able to recognize the VP2 protein. Rabbit sera were able to neutralize CPV in an in vitro infection assay with an efficacy similar to the anti-2L21 neutralizing monoclonal antibody 3C9. Anti-2L21 IgG and seric IgA antibodies were elicited when mice were gavaged with a suspension of pulverized tissues from CTB-2L21 transformed plants. Combined immunization (a single parenteral injection followed by oral boosters) shows that oral boosters help to maintain the anti-2L21 IgG response induced after a single injection, whereas parenteral administration of the antigen primes the subsequent oral boosters by promoting the induction of anti-2L21 seric IgA antibodies. Despite the induced humoral response, antibodies elicited by oral delivery did not show neutralizing capacity in the in vitro assay. The high yield of the fusion protein permits the preparation of a high number of vaccine doses from a single plant and makes feasible the oral vaccination using a small amount of crude plant material. However, a big effort has still to be done to enhance the protective efficacy of subunit vaccines by the oral route.

  16. A Vaccine Therapy for Canine Visceral Leishmaniasis Promoted Significant Improvement of Clinical and Immune Status with Reduction in Parasite Burden

    PubMed Central

    Roatt, Bruno Mendes; Aguiar-Soares, Rodrigo Dian de Oliveira; Reis, Levi Eduardo Soares; Cardoso, Jamille Mirelle de Oliveira; Mathias, Fernando Augusto Siqueira; de Brito, Rory Cristiane Fortes; da Silva, Sydnei Magno; Gontijo, Nelder De Figueiredo; Ferreira, Sidney de Almeida; Valenzuela, Jesus G.; Corrêa-Oliveira, Rodrigo; Giunchetti, Rodolfo Cordeiro; Reis, Alexandre Barbosa

    2017-01-01

    Herein, we evaluated the treatment strategy employing a therapeutic heterologous vaccine composed of antigens of Leishmania braziliensis associated with MPL adjuvant (LBMPL vaccine) for visceral leishmaniasis (VL) in symptomatic dogs naturally infected by Leishmania infantum. Sixteen dogs received immunotherapy with MPL adjuvant (n = 6) or with a vaccine composed of antigens of L. braziliensis associated with MPL (LBMPL vaccine therapy, n = 10). Dogs were submitted to an immunotherapeutic scheme consisting of 3 series composed of 10 subcutaneous doses with 10-day interval between each series. The animals were evaluated before (T0) and 90 days after treatment (T90) for their biochemical/hematological, immunological, clinical, and parasitological variables. Our major results showed that the vaccine therapy with LBMPL was able to restore and normalize main biochemical (urea, AST, ALP, and bilirubin) and hematological (erythrocytes, hemoglobin, hematocrit, and platelets) parameters. In addition, in an ex vivo analysis using flow cytometry, dogs treated with LBMPL vaccine showed increased CD3+ T lymphocytes and their subpopulations (TCD4+ and TCD8+), reduction of CD21+ B lymphocytes, increased NK cells (CD5−CD16+) and CD14+ monocytes. Under in vitro conditions, the animals developed a strong antigen-specific lymphoproliferation mainly by TCD4+ and TCD8+ cells; increasing in both TCD4+IFN-γ+ and TCD8+IFN-γ+ as well as reduction of TCD4+IL-4+ and TCD8+IL-4+ lymphocytes with an increased production of TNF-α and reduced levels of IL-10. Concerning the clinical signs of canine visceral leishmaniasis, the animals showed an important reduction in the number and intensity of the disease signs; increase body weight as well as reduction of splenomegaly. In addition, the LBMPL immunotherapy also promoted a reduction in parasite burden assessed by real-time PCR. In the bone marrow, we observed seven times less parasites in LBMPL animals compared with MPL group. The

  17. A Vaccine Therapy for Canine Visceral Leishmaniasis Promoted Significant Improvement of Clinical and Immune Status with Reduction in Parasite Burden.

    PubMed

    Roatt, Bruno Mendes; Aguiar-Soares, Rodrigo Dian de Oliveira; Reis, Levi Eduardo Soares; Cardoso, Jamille Mirelle de Oliveira; Mathias, Fernando Augusto Siqueira; de Brito, Rory Cristiane Fortes; da Silva, Sydnei Magno; Gontijo, Nelder De Figueiredo; Ferreira, Sidney de Almeida; Valenzuela, Jesus G; Corrêa-Oliveira, Rodrigo; Giunchetti, Rodolfo Cordeiro; Reis, Alexandre Barbosa

    2017-01-01

    Herein, we evaluated the treatment strategy employing a therapeutic heterologous vaccine composed of antigens of Leishmania braziliensis associated with MPL adjuvant (LBMPL vaccine) for visceral leishmaniasis (VL) in symptomatic dogs naturally infected by Leishmania infantum. Sixteen dogs received immunotherapy with MPL adjuvant (n = 6) or with a vaccine composed of antigens of L. braziliensis associated with MPL (LBMPL vaccine therapy, n = 10). Dogs were submitted to an immunotherapeutic scheme consisting of 3 series composed of 10 subcutaneous doses with 10-day interval between each series. The animals were evaluated before (T0) and 90 days after treatment (T90) for their biochemical/hematological, immunological, clinical, and parasitological variables. Our major results showed that the vaccine therapy with LBMPL was able to restore and normalize main biochemical (urea, AST, ALP, and bilirubin) and hematological (erythrocytes, hemoglobin, hematocrit, and platelets) parameters. In addition, in an ex vivo analysis using flow cytometry, dogs treated with LBMPL vaccine showed increased CD3(+) T lymphocytes and their subpopulations (TCD4(+) and TCD8(+)), reduction of CD21(+) B lymphocytes, increased NK cells (CD5(-)CD16(+)) and CD14(+) monocytes. Under in vitro conditions, the animals developed a strong antigen-specific lymphoproliferation mainly by TCD4(+) and TCD8(+) cells; increasing in both TCD4(+)IFN-γ(+) and TCD8(+)IFN-γ(+) as well as reduction of TCD4(+)IL-4(+) and TCD8(+)IL-4(+) lymphocytes with an increased production of TNF-α and reduced levels of IL-10. Concerning the clinical signs of canine visceral leishmaniasis, the animals showed an important reduction in the number and intensity of the disease signs; increase body weight as well as reduction of splenomegaly. In addition, the LBMPL immunotherapy also promoted a reduction in parasite burden assessed by real-time PCR. In the bone marrow, we observed seven times less parasites in LBMPL

  18. Immunotherapy with the saponin enriched-Leishmune vaccine versus immunochemotherapy in dogs with natural canine visceral leishmaniasis.

    PubMed

    Borja-Cabrera, G P; Santos, F N; Santos, F B; Trivellato, Fernando Antonio de A; Kawasaki, Jarbas Kiyoshi A; Costa, Andreia Cerqueira; Castro, Tatiana; Nogueira, F S; Moreira, M A B; Luvizotto, M C R; Palatnik, M; Palatnik-de-Sousa, C B

    2010-01-08

    Leishmune, the first licensed vaccine for prophylaxis against canine visceral leishmaniasis (CVL) and is also immunotherapeutic when used with double saponin adjuvant concentration. The Leishmune therapeutic vaccine was assessed for immunotherapy (IT) in 31 infected dogs and for immunochemotherapy (ICT) in combination with allopurinol or amphotericinB/allopurinol, in 35 dogs. Compared to infected untreated control dogs, at month 3, both treatments increased the proportion of dogs showing intradermal response to Leishmania antigen to a similar extent (from 8 to 67%, in the IT and to 76%, in the ICT groups), and conversely reduced from 100 to 38% (IT) and to 18% (ICT) the proportion of symptomatic cases, from 54 to 12% (IT) and to 15% (ICT) the proportion of parasite evidence in lymph nodes and from 48 to 19% (IT) and 12% (ICT) the proportion of deaths, indicating that the immunotherapy with enriched-Leishmune vaccine promotes the control of the clinical and parasitological signs of CVL rendering most dogs asymptomatic although PCR positive. By month 8, negative lymph node PCR results were obtained in 80% of the ICT-treated dogs, but only in 33% of the IT group (p=0.0253), suggesting that the combination of additional chemotherapy with Leishmune-enriched saponin vaccination abolished, not only the symptoms but also the latent infection condition, curing the dogs. The animals were followed up until 4.5 years after the beginning of the experiment and, compared to the untreated control group at month 3 (12/25 dogs; 48%), a decrease in the rate of CVL deaths was only seen after ICT treatment (7/35 dogs; 20%; 0.0273) but not after IT treatment (10/31 dogs; 32%; p=0.278), pointing out an additional advantage of the ICT treatment with the enriched-Leishmune in the control and cure of CVL.

  19. Vaccination against canine leishmaniosis increases the phagocytic activity, nitric oxide production and expression of cell activation/migration molecules in neutrophils and monocytes.

    PubMed

    Moreira, Marcela L; Costa-Pereira, Christiane; Alves, Marina Luiza Rodrigues; Marteleto, Bruno H; Ribeiro, Vitor M; Peruhype-Magalhães, Vanessa; Giunchetti, Rodolfo C; Martins-Filho, Olindo A; Araújo, Márcio S S

    2016-04-15

    Visceral leishmaniasis (VL) is transmitted by phlebotomine sandfly vectors and domestic dogs serve as a reservoir. The elimination of seropositive dogs has been a recommended strategy for managing the disease in Brazil. A protective canine vaccine would be an important tool for controlling the disease, reducing the parasites available to sandfly vectors and, consequently, reducing the number of human VL cases. Leishmune(®) is an anti-canine Leishmaniosis (VL Canine) vaccine produced by Zoetis (Pfizer, Brazil) that was commercially available in Brazil until 2014. The main goal of the present study was to investigate the protective immunological events induced by vaccination with Leishmune(®) in the time frame of one year. Healthy, non-vaccinated dogs and dogs of 1, 6 and 10 months post-vaccination were evaluated. Results showed that Leishmune(®) induced an increase in phagocytic activity of neutrophils and monocytes and also increased NO production. Immunological events were correlated with functional responses, as high levels of IgG and an increase of the receptor Fcγ were detected. Vaccination induced an increased expression of TLR (2, 4, 5, 9), integrin (CD29, CD49f), activation (MHCII) and co-stimulatory (CD80, CD81) molecules by neutrophils and monocytes. Vaccination led to decrease of IL-4 and an increase of IL-8 production by monocytes and higher IFN-γ and IL-17 production by T-cells. The results suggested that Leishmune(®) was able to induce a long-lasting change in immune response, mediated by supportive immunological events that may be participating in protective immunity against CL.

  20. Safety, tolerability, and immunogenicity of a recombinant, genetically engineered, live-attenuated vaccine against canine blastomycosis.

    PubMed

    Wüthrich, Marcel; Krajaejun, Theerapong; Shearn-Bochsler, Valerie; Bass, Chris; Filutowicz, Hanna I; Legendre, Alfred M; Klein, Bruce S

    2011-05-01

    Blastomycosis is a severe, commonly fatal infection caused by the dimorphic fungus Blastomyces dermatitidis in dogs that live in the United States, Canada, and parts of Africa. The cost of treating an infection can be expensive, and no vaccine against this infection is commercially available. A genetically engineered live-attenuated strain of B. dermatitidis lacking the major virulence factor BAD-1 successfully vaccinates against lethal experimental infection in mice. Here we studied the safety, toxicity, and immunogenicity of this strain as a vaccine in dogs, using 25 beagles at a teaching laboratory and 78 foxhounds in a field trial. In the beagles, escalating doses of live vaccine ranging from 2 × 10⁴ to 2 × 10⁷ yeast cells given subcutaneously were safe and did not disseminate to the lung or induce systemic illness, but a dose of < 2 × 10⁶ yeast cells induced less fever and local inflammation. A vaccine dose of 10⁵ yeast cells was also well tolerated in vaccinated foxhounds who had never had blastomycosis; however, vaccinated dogs with prior infection had more local reactions at the vaccine site. The draining lymph node cells and peripheral blood lymphocytes from vaccinated dogs demonstrated gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and granulocyte-macrophage colony-stimulating factor (GM-CSF) specifically in response to stimulation with Blastomyces antigens. Thus, the live-attenuated vaccine against blastomycosis studied here proved safe, well tolerated, and immunogenic in dogs and merits further studies of vaccine efficacy.

  1. Neutralizing antibodies to phocine distemper virus in Atlantic walruses (Odobenus rosmarus rosmarus) from Arctic Canada.

    PubMed

    Duignan, P J; Saliki, J T; St Aubin, D J; House, J A; Geraci, J R

    1994-01-01

    The first evidence of phocine distemper virus (PDV) infection in Atlantic walruses (Odobenus rosmarus rosmarus) from Nottingham Island, Northwest Territories, Canada, is reported. Blood samples were collected from three male walruses killed by Inuit hunters in the fall of 1990. Differential virus neutralization test for each animal yielded higher titers against PDV than against other members of the Morbillivirus genus including canine distemper, peste des petits ruminants, rinderpest and measles viruses. Thus, PDV infection may be enzootic in walruses of the eastern Canadian Arctic.

  2. Characterization of RD-114 Virus Isolated from a Commercial Canine Vaccine Manufactured Using CRFK Cells ▿

    PubMed Central

    Yoshikawa, Rokusuke; Sato, Eiji; Igarashi, Tatsuhiko; Miyazawa, Takayuki

    2010-01-01

    Recently, we found that several commercial pet vaccines were contaminated with an infectious endogenous retrovirus, RD-114-related virus. Here, we determined the entire nucleotide sequences of RD-114-related viruses isolated from CRFK cells and a vaccine manufactured using CRFK cells. These RD-114-related viruses were nearly identical to the authentic RD-114 virus. PMID:20631117

  3. Vaccination of dogs with canine parvovirus type 2b (CPV-2b) induces neutralising antibody responses to CPV-2a and CPV-2c.

    PubMed

    Wilson, Stephen; Illambas, Joanna; Siedek, Elisabeth; Stirling, Catrina; Thomas, Anne; Plevová, Edita; Sture, Gordon; Salt, Jeremy

    2014-09-22

    Since the identification of canine parvovirus type 2, three variants have subsequently been observed differing from the historical CPV-2 and each other by 1-2 amino acids only. As a result there has been considerable research into differential diagnostics, with some researchers indicating there is a need for new vaccines containing different strains of CPV-2. In this study we investigated whether vaccination with a CPV-2b containing vaccine would induce cross-reactive antibody responses to the other CPV-2 variants. Two studies where dogs were vaccinated with a multivalent vaccine, subsequently challenged with CPV-2b and sera samples analysed are presented. Six week old pups with defined serological status were vaccinated twice, three weeks apart and challenged either 5 weeks (MDA override study) or one year after vaccination (duration of immunity study). Sera samples were collected before each vaccination and at periods throughout each study. In each study the antibody profiles were very similar; serological responses against CPV-2a, CPV-2b and CPV-2c were higher than those for CPV-2. Nevertheless, responses against CPV-2 were well above levels considered clinically protective. In each study dogs also showed a rapid increase in antibody titres following vaccination, reached a plateau following second vaccination with a slight decline to challenge after which rapid anamnestic responses were seen. Evaluation of the serological responses suggests vaccination with CPV-2b would cross-protect against CPV-2a and CPV-2c, as well as against CPV-2 which is now extinct in the field. In conclusion we have demonstrated that vaccination of minimum aged dogs with a multivalent vaccine containing the CPV-2b variant strain will induce serological responses which are cross-reactive against all currently circulating field strains, CPV-2a and CPV-2c, and the now extinct field strain CPV-2.

  4. Antemortem diagnosis of CDV infection by RT-PCR in distemper dogs with neurological deficits without the typical clinical presentation.

    PubMed

    Amude, A M; Alfieri, A A; Alfieri, A F

    2006-08-01

    In dogs with neurological disturbances without myoclonus and extraneural signs, the clinical diagnosis of distemper is difficult perform. Considering the great infectious potential of the disease, the possibility of carrying out an antemortem diagnosis of distemper is important, particularly in hospitalized patients with neurological disease. The present study was carried out to evaluate RT-PCR for antemortem CDV detection in hospitalized dogs with neurological disturbances without the typical findings of distemper. We investigated five dogs with canine distemper virus (CDV) encephalomyelitis, in which the clinical diagnosis was not performed owing to the absence of characteristic signs of the disease, such as myoclonus and systemic signs. We observed an apparent high sensitivity of RT-PCR in urine samples for detection of CDV: four out of five urine samples were RT-PCR positive. The results of the present study suggest that urine is a good biological sample for antemortem CDV detection by RT-PCR in dogs with distemper encephalomyelitis in which the clinical diagnosis is likely to be difficult owing to the absence of suggestive distemper signs. The use of two different body fluids (urine and CSF) may increase the RT-PCR sensitivity for antemortem diagnosis of distemper in such cases.

  5. Genetic diversity and phylogenetic analysis of the attachment glycoprotein of phocine distemper viruses of the 2002 and 1988 epizootics.

    PubMed

    Nielsen, Line; Arctander, Peter; Jensen, Trine H; Dietz, Hans-Henrik; Hammer, Anne S; Banyard, Ashley C; Barrett, Thomas; Blixenkrone-Møller, Merete

    2009-09-01

    To investigate the possible origin and spread of the dramatic re-emergent 2002 distemper epizootic observed among seals in Danish Waters, we have sequenced wild-type genes of the attachment (H) glycoproteins of viruses from both the 2002 and 1988 epizootics. Phylogenetic analysis of the H genes of phocine distemper virus (PDV) together with other morbilliviruses, suggests that the re-emergent 2002 PDV is more closely related to a putative recent ancestral PDV than the 1988 PDV isolates. Moreover, upsurges of distemper disease in land-living carnivores linked in time and locality to the 2002 seal epizootic in Danish Waters was investigated and determined to be caused by canine distemper virus, the closest relative of PDV, revealing no direct epidemiological link to the seal epizootics.

  6. Hemorrhagic and necrotizing hepatitis associated with administration of a modified live canine adenovirus-2 vaccine in a maned wolf (Chrysocyon brachyurus).

    PubMed

    Swenson, Julie; Orr, Kathryn; Bradley, Gregory A

    2012-06-01

    A 15-yr-old, female, maned wolf (Chrysocyon brachyurus) was euthanized after presenting semicomatose with severe, uncontrolled frank hemorrhage from her rectum 6 days following a routine physical examination and vaccination. Histopathology indicated severe hemorrhagic and necrotizing hepatitis with intranuclear basophilic inclusion bodies in the liver that were thought to be consistent with adenoviral infection. Further classification by polymerase chain reaction, immunohistochemical staining, virus isolation, and electron microscopy confirmed the etiologic agent to be canine adenovirus-2. A representative sample of the vaccine that had been used was submitted and sequenced along with the virus isolated from the maned wolf. The sequencing of the etiologic agent that had been isolated from the maned wolf was determined to be the same as the strain of virus used in the production of the modified live vaccine that had been administered 6 days prior to death. From this information, the diagnosis of vaccine-induced adenoviral hepatitis was made. This is the first confirmed case of vaccine-induced canine adenoviral hepatitis in a maned wolf.

  7. Experimental immunization of cats with a recombinant rabies-canine adenovirus vaccine elicits a long-lasting neutralizing antibody response against rabies.

    PubMed

    Hu, R L; Liu, Y; Zhang, S F; Zhang, F; Fooks, A R

    2007-07-20

    During the past decade, human rabies caused by cats has ranked the second highest in China. Several recombinant rabies vaccines have been developed for dogs. However, seldom have these vaccines been assessed or used in cats. In this trial, we report the experimental immunization of a recombinant canine adenovirus-rabies vaccine, CAV-2-E3Delta-RGP, in cats. Thirty cats were inoculated with the recombinant vaccine intramuscularly, orally and intranasally, respectively. Safety and efficacy studies were undertaken using the fluorescent antibody virus neutralization (FAVN) test and evaluated. Results showed that this recombinant vaccine is safe for cats as demonstrated by the three different routes of administration. The vaccine stimulated an efficient humoral response in the vaccinated cats when 10(8.5)PFU/ml of the recombinant vaccine was injected intramuscularly in a single dose. The neutralizing antibody level increased above 0.5IU/ml at 4 weeks after the vaccination. The mean antibody level ranged from 0.96+/-0.26 to 4.47+/-1.57IU/ml among individuals, and the antibody levels were elicited for at least 12 months. After this period, the immunized cats survived the challenge of CVS-24 and an obvious anemnestic and protective immune response was stimulated after the challenge. The immune response occurred later than the inactivated vaccine and the overall antibody level in the vaccinated cats was lower, but it was sufficient to confer protection of cats against infection. This demonstrated that a single, intramuscular dose of CAV-2-E3Delta-RGP stimulated a long-lasting protective immune response in cats and suggested that CAV-2-E3Delta-RGP could be considered as a potential rabies vaccine candidate for cats.

  8. Distempter Vaccination of Dogs: Factors Which Could Cause Vaccine Failure

    PubMed Central

    Povey, R. Charles

    1986-01-01

    Distemper vaccination failures are uncommon. A number of factors which could cause such failure are discussed. The blocking effect of maternal antibody can be expected in 50% of pups at six weeks but is not important after 12 weeks. Among intercurrent infections, the immunosuppressive effect of parvovirus has the potential to precipitate vaccine-induced distemper. Corticosteroids at levels up to 10 mg/kg do not interfere with successful distemper vaccination. Anesthesia or surgery has little effect but use of chloramphenicol or tetracyclines should be avoided. High environmental temperatures can lead to vaccine failure, as can vitamin E deficiency. Excessive environmental exposure to virulent distemper virus can overcome levels of protection which would be adequate under normal circumstances. PMID:17422690

  9. Toxoplasma gondii genotyping in a dog co-infected with distemper virus and ehrlichiosis rickettsia.

    PubMed

    Moretti, Leandro d'Arc; Da Silva, Aristeu Vieira; Ribeiro, Márcio Garcia; Paes, Antonio Carlos; Langoni, Hélio

    2006-01-01

    This paper reports a toxoplasmosis, ehrlichiosis and distemper co-infection in a dog with an exuberant neuropathological clinical picture. Primary involvement was discussed based on information collected in the analysis of the clinical case, such as neurological impairment, epidemiological data, poor immunoprophylactic scheme of the dog affected and the role of these diseases on immunosuppression. Canine distemper and ehrlichiosis were diagnosed based on epidemiologic data, clinical signs, hematological and cytological evaluation. Toxoplasma gondii was isolated and genetically characterized as Type I using restriction analysis (RFLP) with SAG-2 genes. Immunosuppression features of both dogs and human beings are discussed, as well as implications on animal and public health. This is the first report on toxoplasmosis, ehrlichiosis and distemper co-infection in a dog in Brazil, associated with genotyping determination of the T. gondii strain involved.

  10. Veterinary Products Committee working group report on feline and canine vaccination.

    PubMed

    Gaskell, R M; Gettinby, G; Graham, S J; Skilton, D

    2002-02-02

    * The working group was set up by the Veterinary Products Committee in response to current concern in both the public domain and in the scientific community about possible health risks related to the routine vaccination of cats and dogs. The working group concluded that vaccination plays a very valuable role in the prevention and control of the major infectious diseases in cats and dogs. Although adverse reactions to vaccination, including lack of efficacy, occasionally occur, the working group concluded that the overall risk/benefit analysis strongly supports their continued use. * Although for some diseases there is evidence of a longer duration of immunity following vaccination than the one year which is typically recommended on the product literature, there is currently insufficient information to propose revaccination intervals other than those proposed by the manufacturer and approved by the regulatory process. * Notwithstanding this, in view of the occasional occurrence of adverse reactions, the working group recommends that the product literature indicates that the regime for booster vaccinations is based on a minimum duration of immunity rather than a maximum. The working group further recommends that the product literature should state that a risk/benefit assessment should be made for each individual animal by the veterinary surgeon in consultation with the owner with respect to the necessity for each vaccine and the frequency of its use. * The evidence suggests that cats appear to be susceptible to the occasional development of sarcomas at sites of injection and there is some further evidence to suggest that, although other products may be involved, this may be more associated with the use of vaccines containing aluminium-based adjuvants. The working group therefore recommends that a generic warning to this effect should appear on the product literature for all feline vaccines administered by injection. The working group also highlighted the need for

  11. Identification of Borrelia burgdorferi ospC genotypes in canine tissue following tick infestation: Implications for Lyme disease vaccine and diagnostic assay design

    PubMed Central

    Rhodes, D.V.L.; Earnhart, C.G.; Mather, T.N.; Meeus, P.F.M; Marconi, R.T.

    2013-01-01

    In endemic regions, Lyme disease is a potential health threat to dogs. Canine Lyme disease manifests with arthritis-induced lameness, anorexia, fever, lethargy, lymphadenopathy and, in some cases, fatal glomerulonephritis. A recent study revealed that the regional mean for the percentage of seropositive dogs in the Northeast of the USA is 11.6%. The outer surface protein C (OspC) of Lyme disease spirochetes is an important virulence factor required for the establishment of infection in mammals. It is a leading candidate in human and canine Lyme disease vaccine development efforts. Over 30 distinct ospC phyletic types have been defined. It has been hypothesized that ospC genotype may influence mammalian host range. In this study, Ixodes scapularis ticks collected from the field in Rhode Island were assessed for infection with B. burgdorferi. Ticks were fed on purpose bred beagles to repletion and infection of the dogs was assessed through serology and PCR. Tissue biopsies (n = 2) were collected from each dog 49 days post-tick infestation (dpi) and the ospC genotype of the infecting strains determined by direct PCR of DNA extracted from tissue or by PCR after cultivation of spirochetes from biopsy samples. The dominant ospC types associated with B. burgdorferi canine infections differed from those associated with human infection, indicating a relationship between ospC sequence and preferred host range. Knowledge of the most common ospC genotypes associated specifically with infection of dogs will facilitate the rational design of OspC-based canine Lyme disease vaccines and diagnostic assays. PMID:23962611

  12. Identification of Borrelia burgdorferi ospC genotypes in canine tissue following tick infestation: implications for Lyme disease vaccine and diagnostic assay design.

    PubMed

    Rhodes, D V L; Earnhart, C G; Mather, T N; Meeus, P F M; Marconi, R T

    2013-11-01

    In endemic regions, Lyme disease is a potential health threat to dogs. Canine Lyme disease manifests with arthritis-induced lameness, anorexia, fever, lethargy, lymphadenopathy and, in some cases, fatal glomerulonephritis. A recent study revealed that the regional mean for the percentage of seropositive dogs in the north-east of the USA is 11.6%. The outer surface protein C (OspC) of Lyme disease spirochetes is an important virulence factor required for the establishment of infection in mammals. It is a leading candidate in human and canine Lyme disease vaccine development efforts. Over 30 distinct ospC phyletic types have been defined. It has been hypothesized that ospC genotype may influence mammalian host range. In this study, Ixodes scapularis ticks collected from the field in Rhode Island were assessed for infection with B. burgdorferi. Ticks were fed on purpose bred beagles to repletion and infection of the dogs was assessed through serology and PCR. Tissue biopsies (n=2) were collected from each dog 49 days post-tick infestation (dpi) and the ospC genotype of the infecting strains determined by direct PCR of DNA extracted from tissue or by PCR after cultivation of spirochetes from biopsy samples. The dominant ospC types associated with B. burgdorferi canine infections differed from those associated with human infection, indicating a relationship between ospC sequence and preferred host range. Knowledge of the most common ospC genotypes associated specifically with infection of dogs will facilitate the rational design of OspC-based canine Lyme disease vaccines and diagnostic assays.

  13. Evaluation of Live Recombinant Nonpathogenic Leishmania tarentolae Expressing Cysteine Proteinase and A2 Genes as a Candidate Vaccine against Experimental Canine Visceral Leishmaniasis

    PubMed Central

    Shahbazi, Mehdi; Zahedifard, Farnaz; Taheri, Tahereh; Taslimi, Yasaman; Jamshidi, Shahram; Shirian, Sadegh; Mahdavi, Niousha; Hassankhani, Mehdi; Daneshbod, Yahya; Zarkesh-Esfahani, Sayyed Hamid; Papadopoulou, Barbara; Rafati, Sima

    2015-01-01

    Canine Visceral Leishmaniasis (CVL) is a major veterinary and public health problem caused by Leishmania infantum (L. infantum) in many endemic countries. It is a severe chronic disease with generalized parasite spread to the reticuloendothelial system, such as spleen, liver and bone marrow and is often fatal when left untreated. Control of VL in dogs would dramatically decrease infection pressure of L. infantum for humans, since dogs are the main domestic reservoir. In the past decade, various subunits and DNA antigens have been identified as potential vaccine candidates in experimental animal models, but none has been approved for human use so far. In this study, we vaccinated outbreed dogs with a prime-boost regimen based on recombinant L. tarentolae expressing the L. donovani A2 antigen along with cysteine proteinase genes (CPA and CPB without its unusual C-terminal extension (CPB-CTE) and evaluated its immunogenicity and protective immunity against L. infantum infectious challenge. We showed that vaccinated animals produced significantly higher levels of IgG2, but not IgG1, and also IFN-γ and TNF-α, but low IL-10 levels, before and after challenge as compared to control animals. Protection in dogs was also correlated with a strong DTH response and low parasite burden in the vaccinated group. Altogether, immunization with recombinant L. tarentolae A2-CPA-CPB-CTE was proven to be immunogenic and induced partial protection in dogs, hence representing a promising live vaccine candidate against CVL. PMID:26197085

  14. Evaluation of Live Recombinant Nonpathogenic Leishmania tarentolae Expressing Cysteine Proteinase and A2 Genes as a Candidate Vaccine against Experimental Canine Visceral Leishmaniasis.

    PubMed

    Shahbazi, Mehdi; Zahedifard, Farnaz; Taheri, Tahereh; Taslimi, Yasaman; Jamshidi, Shahram; Shirian, Sadegh; Mahdavi, Niousha; Hassankhani, Mehdi; Daneshbod, Yahya; Zarkesh-Esfahani, Sayyed Hamid; Papadopoulou, Barbara; Rafati, Sima

    2015-01-01

    Canine Visceral Leishmaniasis (CVL) is a major veterinary and public health problem caused by Leishmania infantum (L. infantum) in many endemic countries. It is a severe chronic disease with generalized parasite spread to the reticuloendothelial system, such as spleen, liver and bone marrow and is often fatal when left untreated. Control of VL in dogs would dramatically decrease infection pressure of L. infantum for humans, since dogs are the main domestic reservoir. In the past decade, various subunits and DNA antigens have been identified as potential vaccine candidates in experimental animal models, but none has been approved for human use so far. In this study, we vaccinated outbreed dogs with a prime-boost regimen based on recombinant L. tarentolae expressing the L. donovani A2 antigen along with cysteine proteinase genes (CPA and CPB without its unusual C-terminal extension (CPB-CTE) and evaluated its