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Sample records for ai virus infection

  1. Viruses Infecting Reptiles

    PubMed Central

    Marschang, Rachel E.

    2011-01-01

    A large number of viruses have been described in many different reptiles. These viruses include arboviruses that primarily infect mammals or birds as well as viruses that are specific for reptiles. Interest in arboviruses infecting reptiles has mainly focused on the role reptiles may play in the epidemiology of these viruses, especially over winter. Interest in reptile specific viruses has concentrated on both their importance for reptile medicine as well as virus taxonomy and evolution. The impact of many viral infections on reptile health is not known. Koch’s postulates have only been fulfilled for a limited number of reptilian viruses. As diagnostic testing becomes more sensitive, multiple infections with various viruses and other infectious agents are also being detected. In most cases the interactions between these different agents are not known. This review provides an update on viruses described in reptiles, the animal species in which they have been detected, and what is known about their taxonomic positions. PMID:22163336

  2. Viruses infecting reptiles.

    PubMed

    Marschang, Rachel E

    2011-11-01

    A large number of viruses have been described in many different reptiles. These viruses include arboviruses that primarily infect mammals or birds as well as viruses that are specific for reptiles. Interest in arboviruses infecting reptiles has mainly focused on the role reptiles may play in the epidemiology of these viruses, especially over winter. Interest in reptile specific viruses has concentrated on both their importance for reptile medicine as well as virus taxonomy and evolution. The impact of many viral infections on reptile health is not known. Koch's postulates have only been fulfilled for a limited number of reptilian viruses. As diagnostic testing becomes more sensitive, multiple infections with various viruses and other infectious agents are also being detected. In most cases the interactions between these different agents are not known. This review provides an update on viruses described in reptiles, the animal species in which they have been detected, and what is known about their taxonomic positions.

  3. Zika virus infection.

    PubMed

    Pougnet, Laurence; Thill, Chloé; Pougnet, Richard; Auvinet, Henri; Giacardi, Christophe; Drouillard, Isabelle

    2016-12-01

    A 21-year old woman from New-Caledonia had 40 ̊C fever with vomiting, arthralgia, myalgia, and measles-like rash. Etiological analyses showed primary infection with Zika virus. Because of severe clinical presentation, she was hospitalized in the intensive care unit of the Brest military Hospital. Zika virus is mainly transmitted by Aedes mosquitoes. If they settle in Metropolitan France, Zika virus might also spread there.

  4. [ZIKA--VIRUS INFECTION].

    PubMed

    Velev, V

    2016-01-01

    This review summarizes the knowledge of the scientific community for Zika-virus infection. It became popular because of severe congenital damage causes of CNS in newborns whose mothers are infected during pregnancy, as well as the risk of pandemic distribution. Discusses the peculiarities of the biology and ecology of vectors--blood-sucking mosquitoes Aedes; stages in the spread of infection and practical problems which caused during pregnancy. Attention is paid to the recommendations that allow leading national and international medical organizations to deal with the threat Zika-virus infection.

  5. Filter-feeding bivalves can remove avian influenza viruses from water and reduce infectivity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza (AI) viruses are transmitted within wild aquatic bird populations through an indirect fecal-oral route involving fecal-contaminated water. In this study, the influence of filter-feeding bivalves, Corbicula fluminea, on the infectivity of AI virus in water was examined. A single cla...

  6. Viruses infecting marine molluscs.

    PubMed

    Arzul, Isabelle; Corbeil, Serge; Morga, Benjamin; Renault, Tristan

    2017-02-09

    Although a wide range of viruses have been reported in marine molluscs, most of these reports rely on ultrastructural examination and few of these viruses have been fully characterized. The lack of marine mollusc cell lines restricts virus isolation capacities and subsequent characterization works. Our current knowledge is mostly restricted to viruses affecting farmed species such as oysters Crassostrea gigas, abalone Haliotis diversicolor supertexta or the scallop Chlamys farreri. Molecular approaches which are needed to identify virus affiliation have been carried out for a small number of viruses, most of them belonging to the Herpesviridae and birnaviridae families. These last years, the use of New Generation Sequencing approach has allowed increasing the number of sequenced viral genomes and has improved our capacity to investigate the diversity of viruses infecting marine molluscs. This new information has in turn allowed designing more efficient diagnostic tools. Moreover, the development of experimental infection protocols has answered some questions regarding the pathogenesis of these viruses and their interactions with their hosts. Control and management of viral diseases in molluscs mostly involve active surveillance, implementation of effective bio security measures and development of breeding programs. However factors triggering pathogen development and the life cycle and status of the viruses outside their mollusc hosts still need further investigations.

  7. Human Influenza Virus Infections.

    PubMed

    Peteranderl, Christin; Herold, Susanne; Schmoldt, Carole

    2016-08-01

    Seasonal and pandemic influenza are the two faces of respiratory infections caused by influenza viruses in humans. As seasonal influenza occurs on an annual basis, the circulating virus strains are closely monitored and a yearly updated vaccination is provided, especially to identified risk populations. Nonetheless, influenza virus infection may result in pneumonia and acute respiratory failure, frequently complicated by bacterial coinfection. Pandemics are, in contrary, unexpected rare events related to the emergence of a reassorted human-pathogenic influenza A virus (IAV) strains that often causes increased morbidity and spreads extremely rapidly in the immunologically naive human population, with huge clinical and economic impact. Accordingly, particular efforts are made to advance our knowledge on the disease biology and pathology and recent studies have brought new insights into IAV adaptation mechanisms to the human host, as well as into the key players in disease pathogenesis on the host side. Current antiviral strategies are only efficient at the early stages of the disease and are challenged by the genomic instability of the virus, highlighting the need for novel antiviral therapies targeting the pulmonary host response to improve viral clearance, reduce the risk of bacterial coinfection, and prevent or attenuate acute lung injury. This review article summarizes our current knowledge on the molecular basis of influenza infection and disease progression, the key players in pathogenesis driving severe disease and progression to lung failure, as well as available and envisioned prevention and treatment strategies against influenza virus infection.

  8. Gene expression responses to highly pathogenic avian influenza H5N1 virus infections in ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Differences in host response to infection with avian influenza (AI) viruses were investigated by identifying genes differentially expressed in tissues of infected ducks. Clear differences in pathogenicity were observed among ducks inoculated with five H5N1 HPAI viruses. Virus titers in tissues cor...

  9. [West Nile virus infection].

    PubMed

    Pérez Ruiz, Mercedes; Gámez, Sara Sanbonmatsu; Clavero, Miguel Angel Jiménez

    2011-12-01

    West Nile virus (WNV) is an arbovirus usually transmitted by mosquitoes. The main reservoirs are birds, although the virus may infect several vertebrate species, such as horses and humans. Up to 80% of human infections are asymptomatic. The most frequent clinical presentation is febrile illness, and neuroinvasive disease can occur in less than 1% of cases. Spain is considered a high-risk area for the emergence of WNV due to its climate and the passage of migratory birds from Africa (where the virus is endemic). These birds nest surrounding wetlands where populations of possible vectors for the virus are abundant. Diagnosis of human neurological infections can be made by detection of IgM in serum and/or cerebrospinal fluid samples, demonstration of a four-fold increase in IgG antibodies between acute-phase and convalescent-phase serum samples, or by detection of viral genome by reverse transcription-polymerase chain reaction (especially useful in transplant recipients). Since WNV is a biosafety level 3 agent, techniques that involve cell culture are restricted to laboratories with this level of biosafety, such as reference laboratories. The National Program for the Surveillance of WNV Encephalitis allows the detection of virus circulation among birds and vectors in areas especially favorable for the virus, such as wetlands, and provides information for evaluation of the risk of disease in horses and humans.

  10. Filter-feeding bivalves can remove avian influenza viruses from water and reduce infectivity

    PubMed Central

    Faust, Christina; Stallknecht, David; Swayne, David; Brown, Justin

    2009-01-01

    Avian influenza (AI) viruses are believed to be transmitted within wild aquatic bird populations through an indirect faecal–oral route involving contaminated water. This study examined the influence of filter-feeding bivalves, Corbicula fluminea, on the infectivity of AI virus in water. Clams were placed into individual flasks with distilled water inoculated 1:100 with a low pathogenic (LP) AI virus (A/Mallard/MN/190/99 (H3N8)). Viral titres in water with clams were significantly lower at 24 and 48 h post-inoculation compared to LPAI-infected water without clams. To determine whether clams affected the infectivity of AI viruses, 18 wood ducks (Aix sponsa) were divided into test groups and inoculated with a variety of treatments of clam supernatants, whole clams and water exposed to a high pathogenic (HP) AI (A/whooper swan/Mongolia/244/05 (H5N1)). None of the wood ducks inoculated with HPAI-infected water that was filtered by clams or that was inoculated with or fed tissue from these clams exhibited morbidity or mortality. All wood ducks exposed to either HPAI-infected water without clams or the original viral inoculum died. These results indicate that filter-feeding bivalves can remove and reduce the infectivity of AI viruses in water and demonstrate the need to examine biotic environmental factors that can influence AI virus transmission. PMID:19656788

  11. Varicella zoster virus infection

    PubMed Central

    Gershon, Anne A.; Breuer, Judith; Cohen, Jeffrey I.; Cohrs, Randall J.; Gershon, Michael D.; Gilden, Don; Grose, Charles; Hambleton, Sophie; Kennedy, Peter G. E.; Oxman, Michael N.; Seward, Jane F.; Yamanishi, Koichi

    2017-01-01

    Infection with varicella zoster virus (VZV) causes varicella (chickenpox), which can be severe in immunocompromised individuals, infants and adults. Primary infection is followed by latency in ganglionic neurons. During this period, no virus particles are produced and no obvious neuronal damage occurs. Reactivation of the virus leads to virus replication, which causes zoster (shingles) in tissues innervated by the involved neurons, inflammation and cell death — a process that can lead to persistent radicular pain (postherpetic neuralgia). The pathogenesis of postherpetic neuralgia is unknown and it is difficult to treat. Furthermore, other zoster complications can develop, including myelitis, cranial nerve palsies, meningitis, stroke (vasculopathy), retinitis, and gastroenterological infections such as ulcers, pancreatitis and hepatitis. VZV is the only human herpesvirus for which highly effective vaccines are available. After varicella or vaccination, both wild-type and vaccine-type VZV establish latency, and long-term immunity to varicella develops. However, immunity does not protect against reactivation. Thus, two vaccines are used: one to prevent varicella and one to prevent zoster. In this Primer we discuss the pathogenesis, diagnosis, treatment, and prevention of VZV infections, with an emphasis on the molecular events that regulate these diseases. For an illustrated summary of this Primer, visit: http://go.nature.com/14×VI1 PMID:27188665

  12. Giant viruses infecting algae.

    PubMed

    Van Etten, J L; Meints, R H

    1999-01-01

    Paramecium bursaria chlorella virus (PBCV-1) is the prototype of a family of large, icosahedral, plaque-forming, double-stranded-DNA-containing viruses that replicate in certain unicellular, eukaryotic chlorella-like green algae. DNA sequence analysis of its 330, 742-bp genome leads to the prediction that this phycodnavirus has 376 protein-encoding genes and 10 transfer RNA genes. The predicted gene products of approximately 40% of these genes resemble proteins of known function. The chlorella viruses have other features that distinguish them from most viruses, in addition to their large genome size. These features include the following: (a) The viruses encode multiple DNA methyltransferases and DNA site-specific endonucleases; (b) PBCV-1 encodes at least part, if not the entire machinery to glycosylate its proteins; (c) PBCV-1 has at least two types of introns--a self-splicing intron in a transcription factor-like gene and a splicesomal processed type of intron in its DNA polymerase gene. Unlike the chlorella viruses, large double-stranded-DNA-containing viruses that infect marine, filamentous brown algae have a circular genome and a lysogenic phase in their life cycle.

  13. [Zika virus infection during pregnancy].

    PubMed

    Picone, O; Vauloup-Fellous, C; D'Ortenzio, E; Huissoud, C; Carles, G; Benachi, A; Faye, A; Luton, D; Paty, M-C; Ayoubi, J-M; Yazdanpanah, Y; Mandelbrot, L; Matheron, S

    2016-05-01

    A Zika virus epidemic is currently ongoing in the Americas. This virus is linked to congenital infections with potential severe neurodevelopmental dysfunction. However, incidence of fetal infection and whether this virus is responsible of other fetal complications are still unknown. National and international public health authorities recommend caution and several prevention measures. Declaration of Zika virus infection is now mandatory in France. Given the available knowledge on Zika virus, we suggest here a review of the current recommendations for management of pregnancy in case of suspicious or infection by Zika virus in a pregnant woman.

  14. Avian influenza: mixed infections and missing viruses.

    PubMed

    Lindsay, LeAnn L; Kelly, Terra R; Plancarte, Magdalena; Schobel, Seth; Lin, Xudong; Dugan, Vivien G; Wentworth, David E; Boyce, Walter M

    2013-08-05

    A high prevalence and diversity of avian influenza (AI) viruses were detected in a population of wild mallards sampled during summer 2011 in California, providing an opportunity to compare results obtained before and after virus culture. We tested cloacal swab samples prior to culture by matrix real-time PCR, and by amplifying and sequencing a 640bp portion of the hemagglutinin (HA) gene. Each sample was also inoculated into embryonated chicken eggs, and full genome sequences were determined for cultured viruses. While low matrix Ct values were a good predictor of virus isolation from eggs, samples with high or undetectable Ct values also yielded isolates. Furthermore, a single passage in eggs altered the occurrence and detection of viral strains, and mixed infections (different HA subtypes) were detected less frequently after culture. There is no gold standard or perfect reference comparison for surveillance of unknown viruses, and true negatives are difficult to distinguish from false negatives. This study showed that sequencing samples prior to culture increases the detection of mixed infections and enhances the identification of viral strains and sequences that may have changed or even disappeared during culture.

  15. Avian Influenza A Virus Infections in Humans

    MedlinePlus

    ... this? Submit Button Past Newsletters Avian Influenza A Virus Infections in Humans Language: English Español Recommend ... with Avian Influenza A Viruses Avian Influenza A Virus Infections in Humans Although avian influenza A viruses ...

  16. Global Emerging Infection Surveillance and Response (GEIS)- Avian Influenza Pandemic Influenza (AI/PI) Program

    DTIC Science & Technology

    2010-10-01

    pharyngeal swabs: 6% human metapneumonia, 2% adeno viruses . 2% parainfluenza 3%, 34% parainfluenza 1, 8% rhino virus , 2% Corona virus OC 43, 2% RSV B and 2...Silvanos Mukunzi, Denis Mwala and David C. Schnabel. Human parainfluenza virus infections in kenya: epidemiologic aspects. Africa Influenza...characterize respiratory viruses causing influenza-like illness in Kenya, determine etiologies of diarrheal illnesses and the antimicrobial resistance patterns

  17. Avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza (AI) is caused by type A influenza virus, a member of the Orthomyxoviridae family. AI viruses are serologically categorized into 16 hemagglutinin (H1-H16) and 9 neuraminidase (N1-N9) subtypes. All subtypes have been identified in birds. Infections by AI viruses have been reported in ...

  18. Neonatal herpes simplex virus infections.

    PubMed

    Pinninti, Swetha G; Kimberlin, David W

    2013-04-01

    Neonatal herpes simplex virus infections are uncommon, but because of the morbidity and mortality associated with the infection they are often considered in the differential diagnosis of ill neonates. The use of polymerase chain reaction for diagnosis of central nervous system infections and the development of safe and effective antiviral therapy has revolutionized the diagnosis and management of these infants. Initiation of long-term antiviral suppressive therapy in these infants has led to significant improvement in morbidity. This article summarizes the epidemiology of neonatal herpes simplex virus infections and discusses clinical presentation, diagnosis, management, and follow up of infants with neonatal herpes disease.

  19. Respiratory Syncytial Virus Infections

    MedlinePlus

    Respiratory syncytial virus (RSV) causes mild, cold-like symptoms in adults and older healthy children. It can cause serious problems in ... tests can tell if your child has the virus. There is no specific treatment. You should give ...

  20. Soy isoflavones and virus infections

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Isoflavones and their related flavonoid compounds exert antiviral properties in vitro and in vivo against a wide range of viruses. Genistein is, by far, the most studied soy isoflavone in this regard, and it has been shown to inhibit the infectivity of enveloped or nonenveloped viruses, as well as s...

  1. Variation in infectivity and adaptation of wild duck- and poultry-origin high pathogenicity and low pathogenicity avian influenza viruses for poultry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza (AI) viruses vary in their adaptation which impacts transmission between and infection of different bird species. We determine the intranasal mean bird infectious doses (BID50) for 11 high pathogenicity (HP) AI viruses for layer type chickens (LC), and three low pathogenicity (LP) A...

  2. Evidence that life history characteristics of wild birds influence infection and exposure to influenza A viruses.

    PubMed

    Ely, Craig R; Hall, Jeffrey S; Schmutz, Joel A; Pearce, John M; Terenzi, John; Sedinger, James S; Ip, Hon S

    2013-01-01

    We report on life history characteristics, temporal, and age-related effects influencing the frequency of occurrence of avian influenza (AI) viruses in four species of migratory geese breeding on the Yukon-Kuskokwim Delta, Alaska. Emperor geese (Chen canagica), cackling geese (Branta hutchinsii), greater white-fronted geese (Anser albifrons), and black brant (Branta bernicla), were all tested for active infection of AI viruses upon arrival in early May, during nesting in June, and while molting in July and August, 2006-2010 (n = 14,323). Additionally, prior exposure to AI viruses was assessed via prevalence of antibodies from sera samples collected during late summer in 2009 and 2010. Results suggest that geese are uncommonly infected by low pathogenic AI viruses while in Alaska. The percent of birds actively shedding AI viruses varied annually, and was highest in 2006 and 2010 (1-3%) and lowest in 2007, 2008, and 2009 (<0.70%). Contrary to findings in ducks, the highest incidence of infected birds was in late spring when birds first arrived from staging and wintering areas. Despite low prevalence, most geese were previously exposed to AI viruses, as indicated by high levels of seroprevalence during late summer (47%-96% across species; n = 541). Seroprevalence was >95% for emperor geese, a species that spends part of its life cycle in Asia and is endemic to Alaska and the Bering Sea region, compared to 40-60% for the other three species, whose entire life cycles are within the western hemisphere. Birds <45 days of age showed little past exposure to AI viruses, although antibodies were detected in samples from 5-week old birds in 2009. Seroprevalence of known age black brant revealed that no birds <4 years old had seroconverted, compared to 49% of birds ≥4 years of age.

  3. Chikungunya virus infection: an overview.

    PubMed

    Caglioti, Claudia; Lalle, Eleonora; Castilletti, Concetta; Carletti, Fabrizio; Capobianchi, Maria Rosaria; Bordi, Licia

    2013-07-01

    Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus belonging to the Togaviridae family, first isolated in Tanzania in 1952. The main vectors are mosquitoes from the Aedes species. Recently, the establishment of an envelope mutation increased infectivity for A. albopictus. CHIKV has recently re-emerged causing millions of infections in countries around the Indian Ocean characterized by climate conditions favourable to high vector density. Importation of human cases to European regions with high density of suitable arthropod vectors (such as A. albopictus) may trigger autochthonous outbreaks. The clinical signs of CHIKV infection include non-specific flu-like symptoms, and a characteristic rash accompanied by joint pain that may last for a long time after the resolution of the infection. The death rate is not particularly high, but excess mortality has been observed in concomitance with large CHIKV outbreaks. Deregulation of innate defense mechanisms, such as cytokine inflammatory response, may participate in the main clinical signs of CHIKV infection, and the establishment of persistent (chronic) disease. There is no specific therapy, and prevention is the main countermeasure. Prevention is based on insect control and in avoiding mosquito bites in endemic countries. Diagnosis is based on the detection of virus by molecular methods or by virus culture on the first days of infection, and by detection of an immune response in later stages. CHIKV infection must be suspected in patients with compatible clinical symptoms returning from epidemic/endemic areas. Differential diagnosis should take into account the cross-reactivity with other viruses from the same antigenic complex (i.e. O'nyong-nyong virus).

  4. Nitric oxide and virus infection

    PubMed Central

    Akaike, T; Maeda, H

    2000-01-01

    Nitric oxide (NO) has complex and diverse functions in physiological and pathophysiological phenomena. The mechanisms of many events induced by NO are now well defined, so that a fundamental understanding of NO biology is almost established. Accumulated evidence suggests that NO and oxygen radicals such as superoxide are key molecules in the pathogenesis of various infectious diseases. NO biosynthesis, particularly through expression of an inducible NO synthase (iNOS), occurs in a variety of microbial infections. Although antimicrobial activity of NO is appreciated for bacteria and protozoa, NO has opposing effects in virus infections such as influenza virus pneumonia and certain other neurotropic virus infections. iNOS produces an excessive amount of NO for long periods, which allows generation of a highly reactive nitrogen oxide species, peroxynitrite, via a radical coupling reaction of NO with superoxide. Thus, peroxynitrite causes oxidative tissue injury through potent oxidation and nitration reactions of various biomolecules. NO also appears to affect a host's immune response, with immunopathological consequences. For example, overproduction of NO in virus infections in mice is reported to suppress type 1 helper T-cell-dependent immune responses, leading to type 2 helper T-cell-biased immunological host responses. Thus, NO may be a host response modulator rather than a simple antiviral agent. The unique biological properties of NO are further illustrated by our recent data suggesting that viral mutation and evolution may be accelerated by NO-induced oxidative stress. Here, we discuss these multiple roles of NO in pathogenesis of virus infections as related to both non-specific inflammatory responses and immunological host reactions modulated by NO during infections in vivo. PMID:11106932

  5. Dengue virus antibodies enhance Zika virus infection

    PubMed Central

    Paul, Lauren M; Carlin, Eric R; Jenkins, Meagan M; Tan, Amanda L; Barcellona, Carolyn M; Nicholson, Cindo O; Michael, Scott F; Isern, Sharon

    2016-01-01

    For decades, human infections with Zika virus (ZIKV), a mosquito-transmitted flavivirus, were sporadic, associated with mild disease, and went underreported since symptoms were similar to other acute febrile diseases. Recent reports of severe disease associated with ZIKV have greatly heightened awareness. It is anticipated that ZIKV will continue to spread in the Americas and globally where competent Aedes mosquito vectors are found. Dengue virus (DENV), the most common mosquito-transmitted human flavivirus, is both well-established and the source of outbreaks in areas of recent ZIKV introduction. DENV and ZIKV are closely related, resulting in substantial antigenic overlap. Through antibody-dependent enhancement (ADE), anti-DENV antibodies can enhance the infectivity of DENV for certain classes of immune cells, causing increased viral production that correlates with severe disease outcomes. Similarly, ZIKV has been shown to undergo ADE in response to antibodies generated by other flaviviruses. We tested the neutralizing and enhancing potential of well-characterized broadly neutralizing human anti-DENV monoclonal antibodies (HMAbs) and human DENV immune sera against ZIKV using neutralization and ADE assays. We show that anti-DENV HMAbs, cross-react, do not neutralize, and greatly enhance ZIKV infection in vitro. DENV immune sera had varying degrees of neutralization against ZIKV and similarly enhanced ZIKV infection. Our results suggest that pre-existing DENV immunity may enhance ZIKV infection in vivo and may lead to increased disease severity. Understanding the interplay between ZIKV and DENV will be critical in informing public health responses and will be particularly valuable for ZIKV and DENV vaccine design and implementation strategies. PMID:28090318

  6. Dengue virus antibodies enhance Zika virus infection.

    PubMed

    Paul, Lauren M; Carlin, Eric R; Jenkins, Meagan M; Tan, Amanda L; Barcellona, Carolyn M; Nicholson, Cindo O; Michael, Scott F; Isern, Sharon

    2016-12-01

    For decades, human infections with Zika virus (ZIKV), a mosquito-transmitted flavivirus, were sporadic, associated with mild disease, and went underreported since symptoms were similar to other acute febrile diseases. Recent reports of severe disease associated with ZIKV have greatly heightened awareness. It is anticipated that ZIKV will continue to spread in the Americas and globally where competent Aedes mosquito vectors are found. Dengue virus (DENV), the most common mosquito-transmitted human flavivirus, is both well-established and the source of outbreaks in areas of recent ZIKV introduction. DENV and ZIKV are closely related, resulting in substantial antigenic overlap. Through antibody-dependent enhancement (ADE), anti-DENV antibodies can enhance the infectivity of DENV for certain classes of immune cells, causing increased viral production that correlates with severe disease outcomes. Similarly, ZIKV has been shown to undergo ADE in response to antibodies generated by other flaviviruses. We tested the neutralizing and enhancing potential of well-characterized broadly neutralizing human anti-DENV monoclonal antibodies (HMAbs) and human DENV immune sera against ZIKV using neutralization and ADE assays. We show that anti-DENV HMAbs, cross-react, do not neutralize, and greatly enhance ZIKV infection in vitro. DENV immune sera had varying degrees of neutralization against ZIKV and similarly enhanced ZIKV infection. Our results suggest that pre-existing DENV immunity may enhance ZIKV infection in vivo and may lead to increased disease severity. Understanding the interplay between ZIKV and DENV will be critical in informing public health responses and will be particularly valuable for ZIKV and DENV vaccine design and implementation strategies.

  7. Neonatal Herpes Simplex Virus Infection.

    PubMed

    James, Scott H; Kimberlin, David W

    2015-09-01

    Herpes simplex virus (HSV) 1 and HSV-2 infections are highly prevalent worldwide and are characterized by establishing lifelong infection with periods of latency interspersed with periodic episodes of reactivation. Acquisition of HSV by an infant during the peripartum or postpartum period results in neonatal HSV disease, a rare but significant infection that can be associated with severe morbidity and mortality, especially if there is dissemination or central nervous system involvement. Diagnostic and therapeutic advances have led to improvements in mortality and, to a lesser extent, neurodevelopmental outcomes, but room exists for further improvement.

  8. Neonatal herpes simplex virus infection.

    PubMed

    Cherpes, Thomas L; Matthews, Dean B; Maryak, Samantha A

    2012-12-01

    Neonatal herpes, seen roughly in 1 of 3000 live births in the United States, is the most serious manifestation of herpes simplex virus (HSV) infection in the perinatal period. Although acyclovir therapy decreases infant mortality associated with perinatal HSV transmission, development of permanent neurological disabilities is not uncommon. Mother-to-neonate HSV transmission is most efficient when maternal genital tract HSV infection is acquired proximate to the time of delivery, signifying that neonatal herpes prevention strategies need to focus on decreasing the incidence of maternal infection during pregnancy and more precisely identifying infants most likely to benefit from prophylactic antiviral therapy.

  9. Hepatitis Virus Infections in Poultry.

    PubMed

    Yugo, Danielle M; Hauck, Ruediger; Shivaprasad, H L; Meng, Xiang-Jin

    2016-09-01

    Viral hepatitis in poultry is a complex disease syndrome caused by several viruses belonging to different families including avian hepatitis E virus (HEV), duck hepatitis B virus (DHBV), duck hepatitis A virus (DHAV-1, -2, -3), duck hepatitis virus Types 2 and 3, fowl adenoviruses (FAdV), and turkey hepatitis virus (THV). While these hepatitis viruses share the same target organ, the liver, they each possess unique clinical and biological features. In this article, we aim to review the common and unique features of major poultry hepatitis viruses in an effort to identify the knowledge gaps and aid the prevention and control of poultry viral hepatitis. Avian HEV is an Orthohepevirus B in the family Hepeviridae that naturally infects chickens and consists of three distinct genotypes worldwide. Avian HEV is associated with hepatitis-splenomegaly syndrome or big liver and spleen disease in chickens, although the majority of the infected birds are subclinical. Avihepadnaviruses in the family of Hepadnaviridae have been isolated from ducks, snow geese, white storks, grey herons, cranes, and parrots. DHBV evolved with the host as a noncytopathic form without clinical signs and rarely progressed to chronicity. The outcome for DHBV infection varies by the host's ability to elicit an immune response and is dose and age dependent in ducks, thus mimicking the pathogenesis of human hepatitis B virus (HBV) infections and providing an excellent animal model for human HBV. DHAV is a picornavirus that causes a highly contagious virus infection in ducks with up to 100% flock mortality in ducklings under 6 wk of age, while older birds remain unaffected. The high morbidity and mortality has an economic impact on intensive duck production farming. Duck hepatitis virus Types 2 and 3 are astroviruses in the family of Astroviridae with similarity phylogenetically to turkey astroviruses, implicating the potential for cross-species infections between strains. Duck astrovirus (DAstV) causes

  10. Anti-inflammatory and Anti-tumorigenic Effects of Açai Berry in Helicobacter felis-infected mice

    PubMed Central

    Lee, Ju Yup; Kim, Nayoung; Choi, Yoon Jeong; Nam, Ryoung Hee; Lee, Seonmin; Ham, Min Hee; Suh, Ji Hyung; Choi, Yoon Jin; Lee, Hye Seung; Lee, Dong Ho

    2016-01-01

    Background: The aim of this study was to evaluate the anti-inflammatory and anti-tumorigenic effect of açai berry after chronic Helicobacter felis colonization in the stomachs of C57BL/6 mice. Methods: A total of 57 four-week-old female C57BL/6 mice (18 control mice and 39 experimental mice) were used. The mice were administered orogastrically with vehicle only or vehicle containing H. felis, 5 times every other day. After inoculation of H. felis, mice were fed either a standard or an açai-containing diet and then sacrificed at 4, 24, and 52 weeks. The infection status and degree of inflammation were determined by culture and histopathology. The level of gastric mucosal myeloperoxidase (MPO), TNF-α, and interleukin-1β (IL-1β) were measured by ELISA. Results: At 24 weeks after inoculation, mucosal atrophy and mucous metaplasia appeared in all infected mice. At 52 weeks after inoculation, dysplastic change was noted in 10%, 25%, and 50% of mice in the H. felis-control, H. felis-açai 5%, and H. felis-açai 10% groups, respectively. The neutrophil, monocyte, atrophy, and metaplasia grades of infected mice showed no significant difference among the H. felis-infected groups. H. felis-infected mice fed with açai berry showed no significant difference compared with H. felis-infected control mice in gastric mucosal MPO, TNF-α, and IL-1β levels. Conclusions: H. felis that colonized the stomachs of C57BL/6 mice provoked inflammation, and induced mucosal atrophy, metaplasia, and dysplasia. However, açai berry did not effectively prohibit the gastric carcinogenesis which was induced by chronic H. felis infection. PMID:27051649

  11. Orally administered thermostable N-acyl homoserine lactonase from Bacillus sp. strain AI96 attenuates Aeromonas hydrophila infection in zebrafish.

    PubMed

    Cao, Yanan; He, Suxu; Zhou, Zhigang; Zhang, Meichao; Mao, Wei; Zhang, Huitu; Yao, Bin

    2012-03-01

    N-Acylated homoserine lactone (AHL) lactonases are capable of degrading signal molecules involved in bacterial quorum sensing and therefore represent a new approach to control bacterial infection. Here a gene responsible for the AHL lactonase activity of Bacillus sp. strain AI96, 753 bp in length, was cloned and then expressed in Escherichia coli. The deduced amino acid sequence of Bacillus sp. AI96 AiiA (AiiA(AI96)) is most similar to those of other Bacillus sp. AHL lactonases (~80% sequence identity) and was consequently categorized as a member of the metallo-β-lactamase superfamily. AiiA(AI96) maintains ~100% of its activity at 10°C to 40°C at pH 8.0, and it is very stable at 70°C at pH 8.0 for at least 1 h; no other Bacillus AHL lactonase has been found to be stable under these conditions. AiiA(AI96) resists digestion by proteases and carp intestinal juice, and it has broad-spectrum substrate specificity. The supplementation of AiiA(AI96) into fish feed by oral administration significantly attenuated Aeromonas hydrophila infection in zebrafish. This is the first report of the oral administration of an AHL lactonase for the efficient control of A. hydrophila.

  12. Probiotics in respiratory virus infections.

    PubMed

    Lehtoranta, L; Pitkäranta, A; Korpela, R

    2014-08-01

    Viral respiratory infections are the most common diseases in humans. A large range of etiologic agents challenge the development of efficient therapies. Research suggests that probiotics are able to decrease the risk or duration of respiratory infection symptoms. However, the antiviral mechanisms of probiotics are unclear. The purpose of this paper is to review the current knowledge on the effects of probiotics on respiratory virus infections and to provide insights on the possible antiviral mechanisms of probiotics. A PubMed and Scopus database search was performed up to January 2014 using appropriate search terms on probiotic and respiratory virus infections in cell models, in animal models, and in humans, and reviewed for their relevance. Altogether, thirty-three clinical trials were reviewed. The studies varied highly in study design, outcome measures, probiotics, dose, and matrices used. Twenty-eight trials reported that probiotics had beneficial effects in the outcome of respiratory tract infections (RTIs) and five showed no clear benefit. Only eight studies reported investigating viral etiology from the respiratory tract, and one of these reported a significant decrease in viral load. Based on experimental studies, probiotics may exert antiviral effects directly in probiotic-virus interaction or via stimulation of the immune system. Although probiotics seem to be beneficial in respiratory illnesses, the role of probiotics on specific viruses has not been investigated sufficiently. Due to the lack of confirmatory studies and varied data available, more randomized, double-blind, and placebo-controlled trials in different age populations investigating probiotic dose response, comparing probiotic strains/genera, and elucidating the antiviral effect mechanisms are necessary.

  13. Influenza A virus infections in land birds, People's Republic of China

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present assumption is that waterbirds are the primary reservoir for avian influenza (AI) viruses. We reexamined this assumption by sampling and real-time RT-PCR testing of 610 Asian birds of 135 species. We showed that influenza A infections are common among non-waterbird species, emphasizing ...

  14. Pediatric human immunodeficiency virus infection.

    PubMed Central

    Domachowske, J B

    1996-01-01

    In the past decade, an increase in pediatric human immunodeficiency virus (HIV) infection has had a substantial impact on childhood morbidity and mortality worldwide. The vertical transmission of HIV from mother to infant accounts for the vast majority of these cases. Identification of HIV-infected pregnant women needs to be impoved so that appropriate therapy can be initiated for both mothers and infants. While recent data demonstrate a dramatic decrease in HIV transmission from a subset of women treated with zidovudine during pregnancy, further efforts at reducing transmission are desperately needed. This review focuses on vertically transmitted HIV infection in children, its epidemiology, diagnostic criteria, natural history, and clinical manifestations including infectious and noninfectious complications. An overview of the complex medical management of these children ensues, including the use of antiretroviral therapy. Opportunistic infection prophylaxis is reviewed, along with the important role of other supportive therapies. PMID:8894346

  15. BK virus infection in human immunodeficiency virus-infected patients.

    PubMed

    Ledesma, J; Muñoz, P; Garcia de Viedma, D; Cabrero, I; Loeches, B; Montilla, P; Gijon, P; Rodriguez-Sanchez, B; Bouza, E

    2012-07-01

    The aim of this study is to evaluate the prevalence of BK virus (BKV) infection in HIV-positive patients receiving highly active antiretroviral therapy (HAART) in our hospital. The presence of BKV was analysed in urine and plasma samples from 78 non-selected HIV-infected patients. Clinical data were recorded using a pre-established protocol. We used a nested PCR to amplify a specific region of the BKV T-large antigen. Positive samples were quantified using real-time PCR. Mean CD4 count in HIV-infected patients was 472 cells/mm3 and median HIV viral load was <50 copies/mL. BKV viraemia was detected in only 1 HIV-positive patient, but 57.7% (45 out of 78) had BKV viruria, which was more common in patients with CD4 counts>500 cells/mm3 (74.3% vs 25.7%; p=0.007). Viruria was present in 21.7% of healthy controls (5 out of 23 samples, p=0.02). All viral loads were low (<100 copies/mL), and we could not find any association between BKV infection and renal or neurological manifestations. We provide an update on the prevalence of BKV in HIV-infected patients treated with HAART. BKV viruria was more common in HIV-infected patients; however, no role for BKV has been demonstrated in this population.

  16. [Zika virus infection in pregnancy].

    PubMed

    Varjasi, Gabriella; Póka, Róbert

    2017-04-01

    The Zika virus is a flavivirus spread by mosquitoes. Its primary vectors are the Aedes aegypti and the Aedes albopictus. Before 2007 it sporadically caused benign morbidity. Since 2015, it started spreading "explosively" in America, especially in Brazil. In August 2016 they reported cases from New York and Poland, too. Most of the infections don't produce any symptoms, but can cause grave complications. The most important lesion is microcephalia that forms in fetuses. Microcephalia's most serious consequence is mental retardation, which puts great burden on both the family and the society. The viral infection increases the incidence of Guillain-Barré syndrome. This is an acute autoimmune disease which causes demyelination and, in the worst cases, it can also be fatal. Yet we do not possess adequate and specific vaccination nor antiviral therapy, although, since July 2016, the effectiveness of a DNA based vaccine is being tested on humans. More than half of the world's population lives in areas contaminated by infected mosquitoes so there is a great need for the development of an effective method against the vector mosquitoes. Sadly, even the vector control strategies aren't effective enough to push back the epidemic. Pregnant or fertile women must take the highest precautions against mosquito bites, especially if they travel to regions ravaged by the epidemic. The safest solution would be to postpone both the trip and the childbearing. In Europe, the vectors aren't spread enough to cause major threat, except maybe the warmer regions bordered by the Mediterranean Sea. However, it is possible that in the near future other viruses spread by Aedes mosquitoes could appear. Naturally, the travellers and immigrants, who came from endemic regions can also contribute to the spread of the epidemic. Thanks to the changes in global weather, there were reported findings of mosquitoes of the Aedes albopictus species in Hungary, which are slowly invading the continent, although

  17. Virus Infections in the Nervous System

    PubMed Central

    Koyuncu, Orkide O.; Hogue, Ian B.; Enquist, Lynn W.

    2013-01-01

    Virus infections usually begin in peripheral tissues and can invade the mammalian nervous system (NS), spreading into the peripheral (PNS) and more rarely the central nervous systems (CNS). The CNS is protected from most virus infections by effective immune responses and multi-layer barriers. However, some viruses enter the NS with high efficiency via the bloodstream or by directly infecting nerves that innervate peripheral tissues, resulting in debilitating direct and immune-mediated pathology. Most viruses in the NS are opportunistic or accidental pathogens, but a few, most notably the alpha herpesviruses and rabies virus, have evolved to enter the NS efficiently and exploit neuronal cell biology. Remarkably, the alpha herpesviruses can establish quiescent infections in the PNS, with rare but often fatal CNS pathology. Here we review how viruses gain access to and spread in the well-protected CNS, with particular emphasis on alpha herpesviruses, which establish and maintain persistent NS infections. PMID:23601101

  18. [Occult hepatitis C virus infection].

    PubMed

    Carreño García, Vicente; Nebreda, Javier Bartolomé; Aguilar, Inmaculada Castillo; Quiroga Estévez, Juan Antonio

    2011-03-01

    Occult hepatitis C virus (HCV) infection is characterized by the detection of HCV-RNA in liver in the absence of anti-HCV and serum HCV-RNA determined by conventional techniques. The development of a new enzyme immunoassay for the detection of antibodies against a conserved epitope in the HCV core protein, together with the detection of HCV-RNA in peripheral blood mononuclear cells and in serum after concentrating the viral particles by ultracentrifugation, allow diagnosis of more than 90% of patients with occult HCV without the need to perform a liver biopsy. Histological damage in occult HCV infection ranges from minimal changes to liver cirrhosis and hepatocellular carcinoma, although in general this disease is less severe than classical chronic hepatitis C. A significant prevalence of occult HCV infection has been identified in risk groups such as hemodialysis patients and the family members of patients with occult hepatitis C. This occult HCV infection can also be found in subjects without clinical or biochemical evidence of liver disease.

  19. Bell's palsy and infection with rubella virus.

    PubMed Central

    Jamal, G A; Al-Husaini, A

    1983-01-01

    Viral antibody-titres were measured in 28 patients with Bell's palsy seen in Baghdad. These cases were selected to include only those seen within 24 hours from onset. No association with recent viral infection other than rubella virus was demonstrated. Four cases showed immunological evidence of simultaneous rubella virus infection but without other clinical evidence of the disease. PMID:6886708

  20. RNA Viruses Infecting Pest Insects

    Technology Transfer Automated Retrieval System (TEKTRAN)

    RNA viruses are viruses whose genetic material is ribonucleic acid (RNA). RNA viruses may be double or single-stranded based on the type of RNA they contain. Single-stranded RNA viruses can be further grouped into negative sense or positive-sense viruses according to the polarity of their RNA. Fur...

  1. Virus-induced aggregates in infected cells.

    PubMed

    Moshe, Adi; Gorovits, Rena

    2012-10-17

    During infection, many viruses induce cellular remodeling, resulting in the formation of insoluble aggregates/inclusions, usually containing viral structural proteins. Identification of aggregates has become a useful diagnostic tool for certain viral infections. There is wide variety of viral aggregates, which differ by their location, size, content and putative function. The role of aggregation in the context of a specific virus is often poorly understood, especially in the case of plant viruses. The aggregates are utilized by viruses to house a large complex of proteins of both viral and host origin to promote virus replication, translation, intra- and intercellular transportation. Aggregated structures may protect viral functional complexes from the cellular degradation machinery. Alternatively, the activation of host defense mechanisms may involve sequestration of virus components in aggregates, followed by their neutralization as toxic for the host cell. The diversity of virus-induced aggregates in mammalian and plant cells is the subject of this review.

  2. Virus infection speeds: Theory versus experiment

    NASA Astrophysics Data System (ADS)

    Amor, Daniel R.; Fort, Joaquim

    2010-12-01

    In order to explain the speed of Vesicular Stomatitis Virus (VSV) infections, we develop a simple model that improves previous approaches to the propagation of virus infections. For VSV infections, we find that the delay time elapsed between the adsorption of a viral particle into a cell and the release of its progeny has a very important effect. Moreover, this delay time makes the adsorption rate essentially irrelevant in order to predict VSV infection speeds. Numerical simulations are in agreement with the analytical results. Our model satisfactorily explains the experimentally measured speeds of VSV infections.

  3. Hendra Virus Infection in Dog, Australia, 2013

    PubMed Central

    Gabor, Melinda; Poe, Ian; Neale, Kristie; Chaffey, Kim; Finlaison, Deborah S.; Gu, Xingnian; Hick, Paul M.; Read, Andrew J.; Wright, Therese; Middleton, Deborah

    2015-01-01

    Hendra virus occasionally causes severe disease in horses and humans. In Australia in 2013, infection was detected in a dog that had been in contact with an infected horse. Abnormalities and viral RNA were found in the dog’s kidney, brain, lymph nodes, spleen, and liver. Dogs should be kept away from infected horses. PMID:26583697

  4. The Epidemiology of Human Immunodeficiency Virus Infection.

    ERIC Educational Resources Information Center

    Glasner, Peter D.; Kaslow, Richard A.

    1990-01-01

    Reviews epidemiology and natural history of human immunodeficiency virus-Type 1 (HIV-1) infection. Discusses early and late clinical manifestations, diagnosis of infection, incubation and latency periods, and survival time. Reviews data from published literature on distribution of HIV infection in adult United States population and factors that…

  5. Occult hepatitis B virus infection

    PubMed Central

    Kwak, Min-Sun; Kim, Yoon Jun

    2014-01-01

    Occult hepatitis B virus (HBV) infection (OBI) refers to the presence of HBV DNA in the absence of detectable hepatitis B surface antigen. Since OBI was first described in the late 1970s, there has been increasing interest in this topic. The prevalence of OBI varies according to the different endemicity of HBV infection, cohort characteristics, and sensitivity and specificity of the methods used for detection. Although the exact mechanism of OBI has not been proved, intra-hepatic persistence of viral covalently closed circular DNA under the host’s strong immune suppression of HBV replication and gene expression seems to be a cause. OBI has important clinical significance in several conditions. First, OBI can be transmitted through transfusion, organ transplantation including orthotopic liver transplantation, or hemodialysis. Donor screening before blood transfusion, prophylaxis for high-risk organ transplantation recipients, and dialysis-specific infection-control programs should be considered to reduce the risk of transmission. Second, OBI may reactivate and cause acute hepatitis in immunocompromised patients or those receiving chemotherapy. Close HBV DNA monitoring and timely antiviral treatment can prevent HBV reactivation and consequent clinical deterioration. Third, OBI may contribute to the progression of hepatic fibrosis in patients with chronic liver disease including hepatitis C. Finally, OBI seems to be a risk factor for hepatocellular carcinoma by its direct proto-oncogenic effect and by indirectly causing persistent hepatic inflammation and fibrosis. However, this needs further investigation. We review published reports in the literature to gain an overview of the status of OBI and emphasize the clinical importance of OBI. PMID:25544873

  6. Zika Virus Infection: Current Concerns and Perspectives.

    PubMed

    Maharajan, Mari Kannan; Ranjan, Aruna; Chu, Jian Feng; Foo, Wei Lim; Chai, Zhi Xin; Lau, Eileen YinYien; Ye, Heuy Mien; Theam, Xi Jin; Lok, Yen Ling

    2016-12-01

    The Zika virus outbreaks highlight the growing importance need for a reliable, specific and rapid diagnostic device to detect Zika virus, as it is often recognized as a mild disease without being identified. Many Zika virus infection cases have been misdiagnosed or underreported because of the non-specific clinical presentation. The aim of this review was to provide a critical and comprehensive overview of the published peer-reviewed evidence related to clinical presentations, various diagnostic methods and modes of transmission of Zika virus infection, as well as potential therapeutic targets to combat microcephaly. Zika virus is mainly transmitted through bites from Aedes aegypti mosquito. It can also be transmitted through blood, perinatally and sexually. Pregnant women are advised to postpone or avoid travelling to areas where active Zika virus transmission is reported, as this infection is directly linked to foetal microcephaly. Due to the high prevalence of Guillain-Barre syndrome and microcephaly in the endemic area, it is vital to confirm the diagnosis of Zika virus. Zika virus infection had been declared as a public health emergency and of international concern by the World Health Organisation. Governments and agencies should play an important role in terms of investing time and resources to fundamentally understand this infection so that a vaccine can be developed besides raising awareness.

  7. Influenza Virus Infection of Marine Mammals.

    PubMed

    Fereidouni, Sasan; Munoz, Olga; Von Dobschuetz, Sophie; De Nardi, Marco

    2016-03-01

    Interspecies transmission may play a key role in the evolution and ecology of influenza A viruses. The importance of marine mammals as hosts or carriers of potential zoonotic pathogens such as highly pathogenic H5 and H7 influenza viruses is not well understood. The fact that influenza viruses are some of the few zoonotic pathogens known to have caused infection in marine mammals, evidence for direct transmission of influenza A virus H7N7 subtype from seals to man, transmission of pandemic H1N1 influenza viruses to seals and also limited evidence for long-term persistence of influenza B viruses in seal populations without significant genetic change, makes monitoring of influenza viruses in marine mammal populations worth being performed. In addition, such monitoring studies could be a great tool to better understand the ecology of influenza viruses in nature.

  8. Evidence that life history characteristics of wild birds influence infection rates and exposure to influenza A viruses

    USGS Publications Warehouse

    Ely, Craig R.; Hall, Jeffrey S.; Schmutz, Joel A.; Pearce, John M.; Terenzi, John; Sedinger, James S.; Ip, Hon S.

    2013-01-01

    We report on life history characteristics, temporal, and age-related effects influencing the frequency of occurrence of avian influenza (AI) viruses in four species of migratory geese breeding on the Yukon-Kuskokwim Delta, Alaska. Emperor geese (Chen canagica), cackling geese (Branta hutchinsii), greater white-fronted geese (Anser albifrons), and black brant (Branta bernicla), were all tested for active infection of AI viruses upon arrival in early May, during nesting in June, and while molting in July and August, 2006–2010 (n = 14,323). Additionally, prior exposure to AI viruses was assessed via prevalence of antibodies from sera samples collected during late summer in 2009 and 2010. Results suggest that geese are uncommonly infected by low pathogenic AI viruses while in Alaska. The percent of birds actively shedding AI viruses varied annually, and was highest in 2006 and 2010 (1–3%) and lowest in 2007, 2008, and 2009 (95% for emperor geese, a species that spends part of its life cycle in Asia and is endemic to Alaska and the Bering Sea region, compared to 40–60% for the other three species, whose entire life cycles are within the western hemisphere. Birds <45 days of age showed little past exposure to AI viruses, although antibodies were detected in samples from 5-week old birds in 2009. Seroprevalence of known age black brant revealed that no birds <4 years old had seroconverted, compared to 49% of birds ≥4 years of age.

  9. Interferon-γ Inhibits Ebola Virus Infection

    PubMed Central

    Rhein, Bethany A.; Powers, Linda S.; Rogers, Kai; Anantpadma, Manu; Singh, Brajesh K.; Sakurai, Yasuteru; Bair, Thomas; Miller-Hunt, Catherine; Sinn, Patrick; Davey, Robert A.

    2015-01-01

    Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks. PMID:26562011

  10. Interferon-γ Inhibits Ebola Virus Infection.

    PubMed

    Rhein, Bethany A; Powers, Linda S; Rogers, Kai; Anantpadma, Manu; Singh, Brajesh K; Sakurai, Yasuteru; Bair, Thomas; Miller-Hunt, Catherine; Sinn, Patrick; Davey, Robert A; Monick, Martha M; Maury, Wendy

    2015-01-01

    Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks.

  11. Dengue Virus Infection Perturbs Lipid Homeostasis in Infected Mosquito Cells

    SciTech Connect

    Perera, Rushika M.; Riley, Catherine; Isaac, Georgis; Hopf- Jannasch, Amber; Moore, Ronald J.; Weitz, Karl K.; Pasa-Tolic, Ljiljana; Metz, Thomas O.; Adamec, Jiri; Kuhn, Richard J.

    2012-03-22

    Dengue virus causes {approx}50-100 million infections per year and thus is considered one of the most aggressive arthropod-borne human pathogen worldwide. During its replication, dengue virus induces dramatic alterations in the intracellular membranes of infected cells. This phenomenon is observed both in human and vector-derived cells. Using high-resolution mass spectrometry of mosquito cells, we show that this membrane remodeling is directly linked to a unique lipid repertoire induced by dengue virus infection. Specifically, 15% of the metabolites detected were significantly different between DENV infected and uninfected cells while 85% of the metabolites detected were significantly different in isolated replication complex membranes. Furthermore, we demonstrate that intracellular lipid redistribution induced by the inhibition of fatty acid synthase, the rate-limiting enzyme in lipid biosynthesis, is sufficient for cell survival but is inhibitory to dengue virus replication. Lipids that have the capacity to destabilize and change the curvature of membranes as well as lipids that change the permeability of membranes are enriched in dengue virus infected cells. Several sphingolipids and other bioactive signaling molecules that are involved in controlling membrane fusion, fission, and trafficking as well as molecules that influence cytoskeletal reorganization are also up regulated during dengue infection. These observations shed light on the emerging role of lipids in shaping the membrane and protein environments during viral infections and suggest membrane-organizing principles that may influence virus-induced intracellular membrane architecture.

  12. Human immunodeficiency virus infection and pneumothorax

    PubMed Central

    Terzi, Eirini; Zarogoulidis, Konstantinos; Kougioumtzi, Ioanna; Dryllis, Georgios; Kioumis, Ioannis; Pitsiou, Georgia; Machairiotis, Nikolaos; Katsikogiannis, Nikolaos; Tsiouda, Theodora; Madesis, Athanasios; Karaiskos, Theodoros

    2014-01-01

    Pneumothorax is a serious and relatively frequent complication of human immunodeficiency virus (HIV) infection that may associate with increased morbidity and mortality and may prove difficult to manage, especially in patients with acquired immunodeficiency syndrome (AIDS). PMID:25337392

  13. Herpes simplex type-1 virus infection.

    PubMed

    Huber, Michaell A

    2003-06-01

    Oral infection caused by the herpes simplex virus represents one of the more common conditions the dental practitioner will be called upon to manage. Unique in its ability to establish latency and undergo subsequent recurrence, it is an ubiquitous infectious agent for which a cure does not exist. For the immunocompetent patient, herpes virus simplex infection typically represents nothing more than a nuisance. However, for the immunocompromised patient, this infection is associated with increased morbidity and mortality. Recently introduced antiviral drug regimens may reduce the morbidity and potential mortality of the herpes simplex virus, especially in immunocompromised patients. The value of antiviral therapy in the management of recurrent herpes simplex virus infection in the immunocompetent patient remains an area of contentious debate.

  14. Respiratory syncytial virus infection: an innate perspective

    PubMed Central

    Johansson, Cecilia

    2016-01-01

    Respiratory syncytial virus (RSV) is a common cause of upper respiratory tract infection in children and adults. However, infection with this virus sometimes leads to severe lower respiratory disease and is the major cause of infant hospitalisations in the developed world. Several risk factors such as baby prematurity and congenital heart disease are known to predispose towards severe disease but previously healthy, full-term infants can also develop bronchiolitis and viral pneumonia during RSV infection. The causes of severe disease are not fully understood but may include dysregulation of the immune response to the virus, resulting in excessive recruitment and activation of innate and adaptive immune cells that can cause damage. This review highlights recent discoveries on the balancing act of immune-mediated virus clearance versus immunopathology during RSV infection. PMID:28105323

  15. Imported Mayaro virus infection in the Netherlands.

    PubMed

    Hassing, Robert-Jan; Leparc-Goffart, Isabelle; Blank, Sybrandus N; Thevarayan, Subashini; Tolou, Hugues; van Doornum, Gerard; van Genderen, Perry J

    2010-10-01

    A Dutch couple, presenting with persisting arthralgias, temporary fever and rash after a stay in Surinam were diagnosed with Mayaro virus infection. Mayaro virus is a relatively unknown South American Alphavirus responsible for dengue-like clinical features and persisting arthralgias. An important, but probably underappreciated cross-reactivity with other Alphaviruses like Chikungunya virus is present, which may become of clinical importance in the event the various Alphaviruses will have overlapping geographical distributions and in seroprevalence studies.

  16. METHODS USED TO STUDY RESPIRATORY VIRUS INFECTION

    PubMed Central

    Flaño, Emilio; Jewell, Nancy A.; Durbin, Russell K.; Durbin, Joan E.

    2009-01-01

    This unit describes protocols for infecting the mouse respiratory tract, and assaying virus replication and host response in the lung. Respiratory infections are the leading cause of acute illness worldwide, affecting mostly infants and children in developing countries. The purpose of this unit is to provide the readers with a basic strategy and protocols to study the pathogenesis and immunology of respiratory virus infection using the mouse as an animal model. The procedures include: (i) basic techniques for mouse infection, tissue sampling and preservation, (ii) determination of viral titers, isolation and analysis of lymphocytes and dendritic cells using flow-cytometry, and (iii) lung histology, immunohistochemistry and in situ hybridization. PMID:19499505

  17. Herpes simplex virus infection during pregnancy.

    PubMed

    Stephenson-Famy, Alyssa; Gardella, Carolyn

    2014-12-01

    Genital herpes in pregnancy continues to cause significant maternal morbidity, with an increasing number of infections being due to oral-labial transmission of herpes simplex virus (HSV)-1. Near delivery, primary infections with HSV-1 or HSV-2 carry the highest risk of neonatal herpes infection, which is a rare but potentially devastating disease for otherwise healthy newborns. Prevention efforts have been limited by lack of an effective intervention for preventing primary infections and the unclear role of routine serologic testing.

  18. Life-Threatening Sochi Virus Infections, Russia.

    PubMed

    Kruger, Detlev H; Tkachenko, Evgeniy A; Morozov, Vyacheslav G; Yunicheva, Yulia V; Pilikova, Olga M; Malkin, Gennadiy; Ishmukhametov, Aydar A; Heinemann, Patrick; Witkowski, Peter T; Klempa, Boris; Dzagurova, Tamara K

    2015-12-01

    Sochi virus was recently identified as a new hantavirus genotype carried by the Black Sea field mouse, Apodemus ponticus. We evaluated 62 patients in Russia with Sochi virus infection. Most clinical cases were severe, and the case-fatality rate was as high as 14.5%.

  19. Virus Infections of Honeybees Apis Mellifera

    PubMed Central

    Tantillo, Giuseppina; Bottaro, Marilisa; Di Pinto, Angela; Martella, Vito; Di Pinto, Pietro

    2015-01-01

    The health and vigour of honeybee colonies are threatened by numerous parasites (such as Varroa destructor and Nosema spp.) and pathogens, including viruses, bacteria, protozoa. Among honeybee pathogens, viruses are one of the major threats to the health and well-being of honeybees and cause serious concern for researchers and beekeepers. To tone down the threats posed by these invasive organisms, a better understanding of bee viral infections will be of crucial importance in developing effective and environmentally benign disease control strategies. Here we summarize recent progress in the understanding of the morphology, genome organization, transmission, epidemiology and pathogenesis of eight honeybee viruses: Deformed wing virus (DWV) and Kakugo virus (KV); Sacbrood virus (SBV); Black Queen cell virus (BQCV); Acute bee paralysis virus (ABPV); Kashmir bee virus (KBV); Israeli Acute Paralysis Virus (IAPV); Chronic bee paralysis virus (CBPV). The review has been designed to provide researchers in the field with updated information about honeybee viruses and to serve as a starting point for future research. PMID:27800411

  20. DIESEL EXHAUST ENHANCES INFLUENZA VIRUS INFECTIONS IN RESPIRATORY EPITHELIAL CELLS

    EPA Science Inventory

    Several factors, such as age and nutritional status can affect the susceptibility to influenza infections. Moreover, exposure to air pollutants, such as diesel exhaust (DE), has been shown to affect respiratory virus infections in rodent models. Influenza virus primarily infects ...

  1. Internet AIS

    NASA Astrophysics Data System (ADS)

    Filjar, Renato; Desic, Sasa; Pokrajac, Danijela; Cubic, Ivica

    2005-05-01

    Automatic Identification System (AIS) has recently become the leading issue in maritime navigation and traffic management worldwide. The present AIS solution, based on a VHF data communications scheme, provides AIS functionalities for SOLAS (AIS Class A) vessels only in a limited environment defined by radio propagation properties. Here we present a novel approach in AIS development based on current mobile communication technologies. It utilises existing mobile communications equipment that the majority of targetted end-users own and are familiar with. A novel AIS concept aims to offer a transition of AIS data traffic to mobile Internet. An innovative AIS architecture supports AIS data processing, storing and transferring to authorised parties. This enhances not only the operational area, but also provides the global AIS with data transfer security and an improved aids-for-navigation service, with all legally traceable vessels (both AIS Class A and AIS Class B) included in the system. In order to provide the development framework for Internet AIS, a set of essential four use-cases, a communication protocol and the first Internet AIS prototype have been recently developed and are briefly introduced in this article.

  2. High prevalence of occult hepatitis C virus infection in patients with chronic hepatitis B virus infection.

    PubMed

    Castillo, Inmaculada; Bartolomé, Javier; Quiroga, Juan Antonio; Carreño, Vicente

    2013-08-01

    Hepatitis C virus (HCV) infection in the absence of detectable antibodies against HCV and of viral RNA in serum is called occult HCV infection. Its prevalence and clinical significance in chronic hepatitis B virus (HBV) infection is unknown. HCV RNA was tested for in the liver samples of 52 patients with chronic HBV infection and 21 (40 %) of them were positive for viral RNA (occult HCV infection). Liver fibrosis was found more frequently and the fibrosis score was significantly higher in patients with occult HCV than in negative ones, suggesting that occult HCV infection may have an impact on the clinical course of HBV infection.

  3. Acute BRSV infection in young AI bulls: effect on sperm quality.

    PubMed

    Alm, K; Koskinen, E; Vahtiala, S; Andersson, M

    2009-06-01

    Bovine respiratory syncytial virus (BRSV) infection is an important part of the calf pneumonia complex, occasionally affecting even adult cattle. However, the pathogenicity of BRSV in animals older than 6 months is often neglected. Finland is free of many contagious diseases in farm animals, and this gives a good opportunity to study the effects of specific pathogens on bovine reproduction. This report describes the deteriorating effects of BRSV epizootics on sperm morphology and fertility of young dairy bulls (n = 79) at a bull station. More than half of the young bulls had a clinical respiratory disease caused by BRSV during their quarantine when they were 6 months old. Four of seven subsequent quarantine groups were affected. Six months later, when these seropositive bulls (n = 54) came into semen production, they had poorer sperm morphology, and the proportion of normal spermatozoa was 74.1% in BRSV-seropositive animals compared with 81.2% in seronegative bulls (n = 25) (p = 0.035). Field fertility was also slightly affected, the 60-day non-return rates were 75.2% and 76.8% for BRSV seropositive and seronegative bulls respectively (p = 0.014). Potential reasons for lowered sperm quality are discussed here.

  4. Respiratory syncytial virus infection in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine respiratory syncytial virus (bRSV) is a cause of respiratory disease in cattle world-wide. It has an integral role in enzootic pneumonia in young dairy calves and summer pneumonia in nursing beef calves. Furthermore, bRSV infection can predispose calves to secondary bacterial infection by org...

  5. Pathogenesis of Lassa Virus Infection in Guinea Pigs

    DTIC Science & Technology

    1982-08-01

    virus , an arenavirus distantly related to Lassa Lassa fever ...other arenaviruses in animal models (5. 6). In VOL. 37, 1982 LASSA VIRUS INFECTION IN GUINEA PIGS 777S[ iU FIG. 6. (A) Lassa viral antigens in...resem- ent with the hemoconcentration associated with bles human and primate Lassa virus infection other human hemorrhagic fever virus infections. than

  6. Human immunodeficiency virus infection and the liver.

    PubMed

    Crane, Megan; Iser, David; Lewin, Sharon R

    2012-03-27

    Liver disease in human immunodeficiency virus (HIV)-infected individuals encompasses the spectrum from abnormal liver function tests, liver decompensation, with and without evidence of cirrhosis on biopsy, to non-alcoholic liver disease and its more severe form, non-alcoholic steatohepatitis and hepatocellular cancer. HIV can infect multiple cells in the liver, leading to enhanced intrahepatic apoptosis, activation and fibrosis. HIV can also alter gastro-intestinal tract permeability, leading to increased levels of circulating lipopolysaccharide that may have an impact on liver function. This review focuses on recent changes in the epidemiology, pathogenesis and clinical presentation of liver disease in HIV-infected patients, in the absence of co-infection with hepatitis B virus or hepatitis C virus, with a specific focus on issues relevant to low and middle income countries.

  7. Differentiation of infected and vaccinated animals (DIVA) using the NS1 protein of avian influenza virus.

    PubMed

    Avellaneda, Gloria; Mundt, Egbert; Lee, Chang-Won; Jadhao, Samadhan; Suarez, David L

    2010-03-01

    Vaccination against avian influenza (AI) virus, a powerful tool for control of the disease, may result in issues related to surveillance programs and international trade of poultry and poultry products. The use of AI vaccination in poultry would have greater worldwide acceptance if a reliable test were available that clearly discriminated between naturally infected and vaccinated-only animals (DIVA). Because the nonstructural protein (NS1) is expressed in influenza virus-infected cells, and it is not packaged in the virion, it is an attractive candidate for a DIVA differential diagnostic test. The aim of this work was to determine the onset of the antibody response to the NS1 protein in chickens infected with low pathogenic avian influenza (LPAI) virus, and to evaluate the diagnostic potential of a baculovirus-expressed purified NS1 protein in an indirect ELISA-based DIVA strategy. An antibody response against NS1 was first detected 3 wk after infection, but the antibody levels were decreasing rapidly by 5 wk after infection. However, most chickens did not have detectable antibodies in spite of high hemagglutination inhibition (HI) antibody titers in one group. In birds vaccinated with inactivated oil-emulsion vaccines, antibodies against NS1 were not detected before virulent challenge, and only a small percentage of birds seroconverted after homologous LPAI virus challenge. Vaccinated birds challenged with highly pathogenic AI showed a higher NS1 antibody response, but at most only 40% of birds seroconverted against NS1 protein by 3 wk after challenge. Because of the variability of seroconversion and the duration of the antibody response in chickens, the NS1 protein DIVA strategy did not perform as well as expected, and if this strategy were to be used, it would require sampling a higher number of birds to compensate for the lower seroconversion rate.

  8. Infection of phytoplankton by aerosolized marine viruses

    PubMed Central

    Sharoni, Shlomit; Trainic, Miri; Schatz, Daniella; Lehahn, Yoav; Flores, Michel J.; Bidle, Kay D.; Ben-Dor, Shifra; Rudich, Yinon; Vardi, Assaf

    2015-01-01

    Marine viruses constitute a major ecological and evolutionary driving force in the marine ecosystems. However, their dispersal mechanisms remain underexplored. Here we follow the dynamics of Emiliania huxleyi viruses (EhV) that infect the ubiquitous, bloom-forming phytoplankton E. huxleyi and show that EhV are emitted to the atmosphere as primary marine aerosols. Using a laboratory-based setup, we showed that the dynamic of EhV aerial emission is strongly coupled to the host–virus dynamic in the culture media. In addition, we recovered EhV DNA from atmospheric samples collected over an E. huxleyi bloom in the North Atlantic, providing evidence for aerosolization of marine viruses in their natural environment. Decay rate analysis in the laboratory revealed that aerosolized viruses can remain infective under meteorological conditions prevailing during E. huxleyi blooms in the ocean, allowing potential dispersal and infectivity over hundreds of kilometers. Based on the combined laboratory and in situ findings, we propose that atmospheric transport of EhV is an effective transmission mechanism for spreading viral infection over large areas in the ocean. This transmission mechanism may also have an important ecological impact on the large-scale host–virus “arms race” during bloom succession and consequently the turnover of carbon in the ocean. PMID:25964340

  9. Infection of phytoplankton by aerosolized marine viruses.

    PubMed

    Sharoni, Shlomit; Trainic, Miri; Schatz, Daniella; Lehahn, Yoav; Flores, Michel J; Bidle, Kay D; Ben-Dor, Shifra; Rudich, Yinon; Koren, Ilan; Vardi, Assaf

    2015-05-26

    Marine viruses constitute a major ecological and evolutionary driving force in the marine ecosystems. However, their dispersal mechanisms remain underexplored. Here we follow the dynamics of Emiliania huxleyi viruses (EhV) that infect the ubiquitous, bloom-forming phytoplankton E. huxleyi and show that EhV are emitted to the atmosphere as primary marine aerosols. Using a laboratory-based setup, we showed that the dynamic of EhV aerial emission is strongly coupled to the host-virus dynamic in the culture media. In addition, we recovered EhV DNA from atmospheric samples collected over an E. huxleyi bloom in the North Atlantic, providing evidence for aerosolization of marine viruses in their natural environment. Decay rate analysis in the laboratory revealed that aerosolized viruses can remain infective under meteorological conditions prevailing during E. huxleyi blooms in the ocean, allowing potential dispersal and infectivity over hundreds of kilometers. Based on the combined laboratory and in situ findings, we propose that atmospheric transport of EhV is an effective transmission mechanism for spreading viral infection over large areas in the ocean. This transmission mechanism may also have an important ecological impact on the large-scale host-virus "arms race" during bloom succession and consequently the turnover of carbon in the ocean.

  10. Persistent RNA virus infections: do PAMPS drive chronic disease?

    PubMed

    McCarthy, Mary K; Morrison, Thomas E

    2017-02-16

    Chronic disease associated with persistent RNA virus infections represents a key public health concern. While human immunodeficiency virus-1 and hepatitis C virus are perhaps the most well-known examples of persistent RNA viruses that cause chronic disease, evidence suggests that many other RNA viruses, including re-emerging viruses such as chikungunya virus, Ebola virus and Zika virus, establish persistent infections. The mechanisms by which RNA viruses drive chronic disease are poorly understood. Here, we discuss how the persistence of viral RNA may drive chronic disease manifestations via the activation of RNA sensing pathways.

  11. Respiratory syncytial virus infection in adults.

    PubMed

    Falsey, Ann R

    2007-04-01

    Respiratory syncytial virus (RSV) is a common winter time respiratory virus that affects persons of all ages and is the major cause of serious lower respiratory tract infections in young children. However, RSV is also an important pathogen in adults, particularly in the elderly, patients with chronic lung disease, or those with impaired immunity. Clinical features of RSV infections overlap with other respiratory viruses, so laboratory tests are required to establish the diagnosis. Reverse transcriptase polymerase chain reaction (RT-PCR) of samples from nasal swabs, sputum, or bronchoalveolar lavage is a sensitive test to substantiate the diagnosis. Serologies are useful in epidemiological surveys. The clinical course of RSV infections is variable. In infants, RSV presents as bronchiolitis. In adults, mild to moderate upper respiratory tract illness is characteristic. However, severe pneumonia can occur, particularly in the elderly with comorbidities or compromised immune status. Humoral antibodies confer partial immunity to RSV infection and disease severity; cellular immunity is important to eradicate RSV in established infections. Treatment of RSV infections is often supportive. Aerosolized ribavirin is approved for RSV infections in infants; its role in adults is controversial. Infection control measures are critical to limit spread of RSV. Currently, RSV vaccines are not available, but candidate vaccines are being developed.

  12. Global Emerging Infection Surveillance and Response (GEIS)- Avian Influenza Pandemic Influenza (AI/PI) Program

    DTIC Science & Technology

    2008-10-01

    include nine influenza A?s (H3N2), twenty two influenza B?s, parainfluenza viruses, RSV, HSV1, adenoviruses, echoviruses, enteroviruses including...coxsackievirus subtype B and other uncharacterized enteroviruses . Seventy three (73) of these virus isolates have been shared with AFIOH. There is

  13. The management of herpes simplex virus infections.

    PubMed

    Yeung-Yue, Kimberly A; Brentjens, Mathijs H; Lee, Patricia C; Tyring, Stephen K

    2002-04-01

    Herpes simplex virus persists in a latent form for the life of its host, periodically reactivating and often resulting in significant psychosocial distress for the patient. Currently no cure is available. Antiviral therapy is the main treatment modality, used either orally, intravenously, or topically to prohibit further replication of the virus and thereby minimize cellular destruction. However, immunologic advances in the treatment and prevention of herpes simplex infections are promising and continue to be studied.

  14. Peptide inhibitors of dengue virus and West Nile virus infectivity

    PubMed Central

    Hrobowski, Yancey M; Garry, Robert F; Michael, Scott F

    2005-01-01

    Viral fusion proteins mediate cell entry by undergoing a series of conformational changes that result in virion-target cell membrane fusion. Class I viral fusion proteins, such as those encoded by influenza virus and human immunodeficiency virus (HIV), contain two prominent alpha helices. Peptides that mimic portions of these alpha helices inhibit structural rearrangements of the fusion proteins and prevent viral infection. The envelope glycoprotein (E) of flaviviruses, such as West Nile virus (WNV) and dengue virus (DENV), are class II viral fusion proteins comprised predominantly of beta sheets. We used a physio-chemical algorithm, the Wimley-White interfacial hydrophobicity scale (WWIHS) [1] in combination with known structural data to identify potential peptide inhibitors of WNV and DENV infectivity that target the viral E protein. Viral inhibition assays confirm that several of these peptides specifically interfere with target virus entry with 50% inhibitory concentration (IC50) in the 10 μM range. Inhibitory peptides similar in sequence to domains with a significant WWIHS scores, including domain II (IIb), and the stem domain, were detected. DN59, a peptide corresponding to the stem domain of DENV, inhibited infection by DENV (>99% inhibition of plaque formation at a concentrations of <25 μM) and cross-inhibition of WNV fusion/infectivity (>99% inhibition at <25 μM) was also demonstrated with DN59. However, a potent WNV inhibitory peptide, WN83, which corresponds to WNV E domain IIb, did not inhibit infectivity by DENV. Additional results suggest that these inhibitory peptides are noncytotoxic and act in a sequence specific manner. The inhibitory peptides identified here can serve as lead compounds for the development of peptide drugs for flavivirus infection. PMID:15927084

  15. Parainfluenza Virus 5 Expressing the G Protein of Rabies Virus Protects Mice after Rabies Virus Infection

    PubMed Central

    Huang, Ying; Chen, Zhenhai; Huang, Junhua

    2014-01-01

    Rabies remains a major public health threat around the world. Once symptoms appear, there is no effective treatment to prevent death. In this work, we tested a recombinant parainfluenza virus 5 (PIV5) strain expressing the glycoprotein (G) of rabies (PIV5-G) as a therapy for rabies virus infection: we have found that PIV5-G protected mice as late as 6 days after rabies virus infection. PIV5-G is a promising vaccine for prevention and treatment of rabies virus infection. PMID:25552723

  16. Respiratory virus infection among hematopoietic cell transplant recipients: evidence for asymptomatic parainfluenza virus infection.

    PubMed

    Peck, Angela J; Englund, Janet A; Kuypers, Jane; Guthrie, Katherine A; Corey, Lawrence; Morrow, Rhoda; Hackman, Robert C; Cent, Anne; Boeckh, Michael

    2007-09-01

    The incidence of respiratory virus infection after hematopoietic cell transplantation (HCT) has probably been underestimated with conventional testing methods in symptomatic patients. This prospective study assessed viral infection episodes by testing weekly respiratory samples collected from HCT recipients, with and without symptoms reported by questionnaire, for 100 days after HCT. Samples were tested by culture and direct fluorescent antibody testing for respiratory syncytial virus (RSV), parainfluenza virus (PIV), and influenza A and B, and by quantitative reverse transcription-polymerase chain reaction for RSV, PIV, influenza A and B, and metapneumovirus (MPV). Of 122 patients, 30 (25%) had 32 infection episodes caused by RSV (5), PIV (17), MPV (6), influenza (3), RSV, or influenza (1). PIV, with a cumulative incidence estimate of 17.9%, was the only virus for which asymptomatic infection was detected. Lower virus copy number in patients with no or one symptom compared with 2 or more symptoms was found for all viruses in all patients (P < .001), with PIV infection having a similar virus-specific comparison (P = .004). Subclinical infection with PIV may help explain why infection-control programs that emphasize symptoms are effective against RSV and influenza but often not against PIV.

  17. Small molecule inhibitors of ebola virus infection.

    PubMed

    Picazo, Edwige; Giordanetto, Fabrizio

    2015-02-01

    Ebola viruses are extremely virulent and highly transmissible. They are responsible for sporadic outbreaks of severe hemorrhagic fevers with human mortality rates of up to 90%. No prophylactic or therapeutic treatments in the form of vaccine, biologicals or small molecule, currently exist. Yet, a wealth of antiviral research on ebola virus is being generated and potential inhibitors have been identified in biological screening and medicinal chemistry programs. Here, we detail the state-of-the-art in small molecule inhibitors of ebola virus infection, with >60 examples, including approved drugs, compounds currently in clinical trials, and more exploratory leads, and summarize the associated in vitro and in vivo evidence for their effectiveness.

  18. Immune responses and Lassa virus infection.

    PubMed

    Russier, Marion; Pannetier, Delphine; Baize, Sylvain

    2012-11-05

    Lassa fever is a hemorrhagic fever endemic to West Africa and caused by Lassa virus, an Old World arenavirus. It may be fatal, but most patients recover from acute disease and some experience asymptomatic infection. The immune mechanisms associated with these different outcomes have not yet been fully elucidated, but considerable progress has recently been made, through the use of in vitro human models and nonhuman primates, the only relevant animal model that mimics the pathophysiology and immune responses induced in patients. We discuss here the roles of the various components of the innate and adaptive immune systems in Lassa virus infection and in the control of viral replication and pathogenesis.

  19. Maternal and neonatal herpes simplex virus infections.

    PubMed

    Pinninti, Swetha G; Kimberlin, David W

    2013-02-01

    Genital herpes infections are extremely common worldwide and ~22% of pregnant women are infected with herpes simplex virus. Eighty percent of those affected with genital herpes are unaware of being infected. The most devastating consequence of maternal genital herpes is neonatal herpes disease. Fortunately, neonatal herpes simplex infections are uncommon but due to the morbidity and mortality associated with the infection are often considered in the differential diagnosis of ill neonates. The use of polymerase chain reaction assay for diagnosis of central nervous system infections and the development of safe and effective antiviral therapy have revolutionized the diagnosis and management of these infants. Most recently, the initiation of long-term antiviral suppressive therapy in these infants has led to significant improvement in morbidity. This review will summarize the epidemiology of maternal and neonatal herpes infections and discuss clinical presentation, diagnosis, management, and follow-up of infants with neonatal herpes disease.

  20. Pathogenesis of human immunodeficiency virus infection.

    PubMed Central

    Levy, J A

    1993-01-01

    The lentivirus human immunodeficiency virus (HIV) causes AIDS by interacting with a large number of different cells in the body and escaping the host immune response against it. HIV is transmitted primarily through blood and genital fluids and to newborn infants from infected mothers. The steps occurring in infection involve an interaction of HIV not only with the CD4 molecule on cells but also with other cellular receptors recently identified. Virus-cell fusion and HIV entry subsequently take place. Following virus infection, a variety of intracellular mechanisms determine the relative expression of viral regulatory and accessory genes leading to productive or latent infection. With CD4+ lymphocytes, HIV replication can cause syncytium formation and cell death; with other cells, such as macrophages, persistent infection can occur, creating reservoirs for the virus in many cells and tissues. HIV strains are highly heterogeneous, and certain biologic and serologic properties determined by specific genetic sequences can be linked to pathogenic pathways and resistance to the immune response. The host reaction against HIV, through neutralizing antibodies and particularly through strong cellular immune responses, can keep the virus suppressed for many years. Long-term survival appears to involve infection with a relatively low-virulence strain that remains sensitive to the immune response, particularly to control by CD8+ cell antiviral activity. Several therapeutic approaches have been attempted, and others are under investigation. Vaccine development has provided some encouraging results, but the observations indicate the major challenge of preventing infection by HIV. Ongoing research is necessary to find a solution to this devastating worldwide epidemic. Images PMID:8464405

  1. Control of viruses infecting grapevine.

    PubMed

    Maliogka, Varvara I; Martelli, Giovanni P; Fuchs, Marc; Katis, Nikolaos I

    2015-01-01

    Grapevine is a high value vegetatively propagated fruit crop that suffers from numerous viruses, including some that seriously affect the profitability of vineyards. Nowadays, 64 viruses belonging to different genera and families have been reported in grapevines and new virus species will likely be described in the future. Three viral diseases namely leafroll, rugose wood, and infectious degeneration are of major economic importance worldwide. The viruses associated with these diseases are transmitted by mealybugs, scale and soft scale insects, or dagger nematodes. Here, we review control measures of the major grapevine viral diseases. More specifically, emphasis is laid on (i) approaches for the production of clean stocks and propagative material through effective sanitation, robust diagnosis, as well as local and regional certification efforts, (ii) the management of vectors of viruses using cultural, biological, and chemical methods, and (iii) the production of resistant grapevines mainly through the application of genetic engineering. The benefits and limitations of the different control measures are discussed with regard to accomplishments and future research directions.

  2. Hepatitis B virus infection in isolated Afro-Brazilian communities.

    PubMed

    Motta-Castro, Ana R C; Martins, Regina M B; Yoshida, Clara F T; Teles, Sheila A; Paniago, Anamaria M; Lima, Kátia M B; Gomes, Selma A

    2005-10-01

    The prevalence and genotypes of hepatitis B virus (HBV) have distinct geographical distribution. In Brazil, some African-descendants have been maintained as small isolated communities since the slavery period. In this study, HBV infection among these communities of African origin was examined. Individuals (1,058) living in 12 communities were interviewed and serum samples screened for the presence of HBV markers. HBsAg-positive sera were tested for HBV DNA by PCR and positive samples were genotyped by restriction fragment length polymorphism (RFLP). The overall prevalence of HBV infection was 19.8% (95% CI: 17.5-22.3), ranging from 5.5% to 42.4%, depending on the communities studied. Multivariate analysis of risk factors showed that increasing age, family history of hepatitis, and sexual activity were associated significantly with this infection. HBsAg was detected in 23/1,058 (2.2%) individuals. HBV DNA was present in 2/2 of HBeAg-positive serum samples and in 18/21 (85.7%) anti-HBe-positive samples. All HBV isolates belonged to genotype A, subtype Aa. Three RFLP patterns were identified: AI (17 isolates), AIV (1 isolate), and AVI (2 isolates). These findings suggest a common introduction of HBV during the slave trade from Africa to Brazil.

  3. Plant virus infections control stomatal development

    NASA Astrophysics Data System (ADS)

    Murray, Rose R.; Emblow, Mark S. M.; Hetherington, Alistair M.; Foster, Gary D.

    2016-09-01

    Stomata are important regulators of carbon dioxide uptake and transpirational water loss. They also represent points of vulnerability as bacterial and fungal pathogens utilise this natural opening as an entry portal, and thus have an increasingly complex relationship. Unlike the situation with bacterial and fungal pathogens, we know very little about the role of stomata in viral infection. Here we report findings showing that viral infection influences stomatal development in two susceptible host systems (Nicotiana tabacum with TMV (Tobacco mosaic virus), and Arabidopsis thaliana with TVCV (Turnip vein-clearing virus)), but not in resistant host systems (Nicotiana glutinosa and Chenopodium quinoa with TMV). Virus infected plants had significantly lower stomatal indices in systemic leaves of susceptible systems; N. tabacum 9.8% reduction and A. thaliana 12.3% reduction, but not in the resistant hosts. Stomatal density in systemic leaves was also significantly reduced in virus infected A. thaliana by 19.6% but not in N. tabacum or the resistant systems. In addition, transpiration rate was significantly reduced in TMV infected N. tabacum.

  4. Plant virus infections control stomatal development

    PubMed Central

    Murray, Rose R.; Emblow, Mark S. M.; Hetherington, Alistair M.; Foster, Gary D.

    2016-01-01

    Stomata are important regulators of carbon dioxide uptake and transpirational water loss. They also represent points of vulnerability as bacterial and fungal pathogens utilise this natural opening as an entry portal, and thus have an increasingly complex relationship. Unlike the situation with bacterial and fungal pathogens, we know very little about the role of stomata in viral infection. Here we report findings showing that viral infection influences stomatal development in two susceptible host systems (Nicotiana tabacum with TMV (Tobacco mosaic virus), and Arabidopsis thaliana with TVCV (Turnip vein-clearing virus)), but not in resistant host systems (Nicotiana glutinosa and Chenopodium quinoa with TMV). Virus infected plants had significantly lower stomatal indices in systemic leaves of susceptible systems; N. tabacum 9.8% reduction and A. thaliana 12.3% reduction, but not in the resistant hosts. Stomatal density in systemic leaves was also significantly reduced in virus infected A. thaliana by 19.6% but not in N. tabacum or the resistant systems. In addition, transpiration rate was significantly reduced in TMV infected N. tabacum. PMID:27687773

  5. Marine Viruses that infect Eukaryotic Microalgae.

    PubMed

    Kimura, Kei; Tomaru, Yuji

    2015-01-01

    Marine microalgae, in general, explain large amount of the primary productions on the planet. Their huge biomass through photosynthetic activities is significant to understand the global geochemical cycles. Many researchers are, therefore, focused on studies of marine microalgae, i.e. phytoplankton. Since the first report of high abundance of viruses in the sea at late 1980's, the marine viruses have recognized as an important decreasing factor of its host populations. They seem to be composed of diverse viruses infectious to different organism groups; most of them are considered to be phages infectious to prokaryotes, and viruses infecting microalgae might be ranked in second level. Over the last quarter of a century, the knowledge on marine microalgal viruses has been accumulated in many aspects. Until today, ca. 40 species of marine microalgal viruses have been discovered, including dsDNA, ssDNA, dsRNA and ssRNA viruses. Their features are unique and comprise new ideas and discoveries, indicating that the marine microalgal virus research is still an intriguing unexplored field. In this review, we summarize their basic biology and ecology, and discuss how and what we should research in this area for further progress.

  6. Preparation of mucosal nanoparticles and polymer-based inactivated vaccine for Newcastle disease and H9N2 AI viruses

    PubMed Central

    Naggar, Heba M. El; Madkour, Mohamed Sayed; Hussein, Hussein Ali

    2017-01-01

    Aim: To develop a mucosal inactivated vaccines for Newcastle disease (ND) and H9N2 viruses to protect against these viruses at sites of infections through mucosal immunity. Materials and Methods: In this study, we prepared two new formulations for mucosal bivalent inactivated vaccine formulations for Newcastle and Avian Influenza (H9N2) based on the use of nanoparticles and polymer adjuvants. The prepared vaccines were delivered via intranasal and spray routes of administration in specific pathogen-free chickens. Cell-mediated and humoral immune response was measured as well as challenge trial was carried out. In addition, ISA71 water in oil was also evaluated. Results: Our results showed that the use of spray route as vaccination delivery method of polymer and nanoparticles Montanide™ adjuvants revealed that it enhanced the cell mediated immune response as indicated by phagocytic activity, gamma interferon and interleukin 6 responses and induced protection against challenge with Newcastle and Avian Influenza (H9N2) viruses. Conclusion: The results of this study demonstrate the potentiality of polymer compared to nanoparticles adjuvantes when used via spray route. Mass application of such vaccines will add value to improve the vaccination strategies against ND virus and Avian influenza viruses. PMID:28344402

  7. Infection of Bergmann glia in the cerebellum of a skunk experimentally infected with street rabies virus.

    PubMed Central

    Jackson, A C; Phelan, C C; Rossiter, J P

    2000-01-01

    Rabies virus is a highly neuronotropic virus and glial cell infection is not prominent in the central nervous system (CNS). Paraffin-embedded tissues from the cerebella of skunks experimentally infected with either a skunk salivary gland isolate of street rabies virus or the challenge virus standard (CVS) strain of fixed rabies virus were examined with immunoperoxidase staining for rabies virus antigen by using an anti-rabies virus nucleocapsid protein monoclonal antibody. A skunk infected with street rabies virus showed prominent infection of Bergmann glia. Although infected Purkinje cells were observed, they usually demonstrated a relatively small amount of antigen in their perikarya. A CVS-infected skunk showed many intensely labeled Purkinje cells and a relatively small number of infected Bergmann glia. These findings indicate that although rabies virus is a highly neuronotropic virus, street rabies virus strains do not always demonstrate strict neuronotropism in the central nervous system. Images Figure 1. PMID:11041500

  8. Infection of Bergmann glia in the cerebellum of a skunk experimentally infected with street rabies virus.

    PubMed

    Jackson, A C; Phelan, C C; Rossiter, J P

    2000-10-01

    Rabies virus is a highly neuronotropic virus and glial cell infection is not prominent in the central nervous system (CNS). Paraffin-embedded tissues from the cerebella of skunks experimentally infected with either a skunk salivary gland isolate of street rabies virus or the challenge virus standard (CVS) strain of fixed rabies virus were examined with immunoperoxidase staining for rabies virus antigen by using an anti-rabies virus nucleocapsid protein monoclonal antibody. A skunk infected with street rabies virus showed prominent infection of Bergmann glia. Although infected Purkinje cells were observed, they usually demonstrated a relatively small amount of antigen in their perikarya. A CVS-infected skunk showed many intensely labeled Purkinje cells and a relatively small number of infected Bergmann glia. These findings indicate that although rabies virus is a highly neuronotropic virus, street rabies virus strains do not always demonstrate strict neuronotropism in the central nervous system.

  9. Origin of the transmitted virus in HIV infection: infected cells versus cell-free virus.

    PubMed

    Sagar, Manish

    2014-12-15

    All human immunodeficiency virus type 1 (HIV-1)-infected inocula, such as genital secretions, breast milk, and blood, contain both cell-free virus and infected cells. The relative contributions of cell-free and/or cell-associated virus in establishing an infection in a naive host during the different modes of HIV-1 acquisition remains unclear. Studies aim to elucidate the source of the acquired virus because strategies to prevent acquisition may have differential efficacy against the different modes of transmission. In this review, I will detail some of the challenges in identifying the source of the transmitted virus, genotypic and phenotypic differences among cell-free compared with cell-associated HIV-1, and implications on the efficacy for prevention strategies.

  10. Zika virus infection of Hofbauer cells.

    PubMed

    Simoni, Michael K; Jurado, Kellie Ann; Abrahams, Vikki M; Fikrig, Erol; Guller, Seth

    2017-02-01

    Recent studies have linked antenatal infection with Zika virus (ZIKV) with major adverse fetal and neonatal outcomes, including microcephaly. There is a growing consensus for the existence of a congenital Zika syndrome (CZS). Previous studies have indicated that non-placental macrophages play a key role in the replication of dengue virus (DENV), a closely related flavivirus. As the placenta provides the conduit for vertical transmission of certain viruses, and placental Hofbauer cells (HBCs) are fetal-placental macrophages located adjacent to fetal capillaries, it is not surprising that several recent studies have examined infection of HBCs by ZIKV. In this review, we describe congenital abnormalities associated with ZIKV infection, the role of HBCs in the placental response to infection, and evidence for the susceptibility of HBCs to ZIKV infection. We conclude that HBCs may contribute to the spread of ZIKV in placenta and promote vertical transmission of ZIKV, ultimately compromising fetal and neonatal development and function. Current evidence strongly suggests that further studies are warranted to dissect the specific molecular mechanism through which ZIKV infects HBCs and its potential impact on the development of CZS.

  11. Avian Influenza Virus Infection of Immortalized Human Respiratory Epithelial Cells Depends upon a Delicate Balance between Hemagglutinin Acid Stability and Endosomal pH.

    PubMed

    Daidoji, Tomo; Watanabe, Yohei; Ibrahim, Madiha S; Yasugi, Mayo; Maruyama, Hisataka; Masuda, Taisuke; Arai, Fumihito; Ohba, Tomoyuki; Honda, Ayae; Ikuta, Kazuyoshi; Nakaya, Takaaki

    2015-04-24

    The highly pathogenic avian influenza (AI) virus, H5N1, is a serious threat to public health worldwide. Both the currently circulating H5N1 and previously circulating AI viruses recognize avian-type receptors; however, only the H5N1 is highly infectious and virulent in humans. The mechanism(s) underlying this difference in infectivity remains unclear. The aim of this study was to clarify the mechanisms responsible for the difference in infectivity between the current and previously circulating strains. Primary human small airway epithelial cells (SAECs) were transformed with the SV40 large T-antigen to establish a series of clones (SAEC-Ts). These clones were then used to test the infectivity of AI strains. Human SAEC-Ts could be broadly categorized into two different types based on their susceptibility (high or low) to the viruses. SAEC-T clones were poorly susceptible to previously circulating AI but were completely susceptible to the currently circulating H5N1. The hemagglutinin (HA) of the current H5N1 virus showed greater membrane fusion activity at higher pH levels than that of previous AI viruses, resulting in broader cell tropism. Moreover, the endosomal pH was lower in high susceptibility SAEC-T clones than that in low susceptibility SAEC-T clones. Taken together, the results of this study suggest that the infectivity of AI viruses, including H5N1, depends upon a delicate balance between the acid sensitivity of the viral HA and the pH within the endosomes of the target cell. Thus, one of the mechanisms underlying H5N1 pathogenesis in humans relies on its ability to fuse efficiently with the endosomes in human airway epithelial cells.

  12. Severe Thrombocytopenia after Zika Virus Infection, Guadeloupe, 2016

    PubMed Central

    Boyer Chammard, Timothée; Schepers, Kinda; Breurec, Sébastien; Messiaen, Thierry; Destrem, Anne-Laure; Mahevas, Matthieu; Soulillou, Adrien; Janaud, Ludovic; Curlier, Elodie; Herrmann-Storck, Cécile

    2017-01-01

    Severe thrombocytopenia during or after the course of Zika virus infection has been rarely reported. We report 7 cases of severe thrombocytopenia and hemorrhagic signs and symptoms in Guadeloupe after infection with this virus. Clinical course and laboratory findings strongly suggest a causal link between Zika virus infection and immune-mediated thrombocytopenia. PMID:27997330

  13. Severe Thrombocytopenia after Zika Virus Infection, Guadeloupe, 2016.

    PubMed

    Boyer Chammard, Timothée; Schepers, Kinda; Breurec, Sébastien; Messiaen, Thierry; Destrem, Anne-Laure; Mahevas, Matthieu; Soulillou, Adrien; Janaud, Ludovic; Curlier, Elodie; Herrmann-Storck, Cécile; Hoen, Bruno

    2017-04-01

    Severe thrombocytopenia during or after the course of Zika virus infection has been rarely reported. We report 7 cases of severe thrombocytopenia and hemorrhagic signs and symptoms in Guadeloupe after infection with this virus. Clinical course and laboratory findings strongly suggest a causal link between Zika virus infection and immune-mediated thrombocytopenia.

  14. Hepatitis B virus infection in multitransfused haemophiliacs.

    PubMed Central

    Nebbia, G; Moroni, G A; Simoni, L; Belli, M; Carnelli, V

    1986-01-01

    A longitudinal study of 44 haemophilic children, all in a treatment programme with factor concentrates, was undertaken to evaluate the occurrence, characteristics, and evolution of hepatitis B virus (HBV) infection. Twenty four children (55%) (group I) showed signs of HBV infection, while 20 (45%) (group II) did not. Age at onset of treatment, number of infusions, and total amount of concentrate received did not show significant differences between the two groups. In group I only four children (16%) had symptomatic acute hepatitis. Chronic liver disease was present in nine patients (38% of infected children). The early age of infection would seem to be an important factor for predicting chronic evolution. Evidence of delta infection in three children with severe liver disease seemed to confirm the high pathogenicity of this agent. Because of the risks associated with chronic HBV infection a careful follow up of patients positive for hepatitis B surface antigen is mandatory. PMID:3089179

  15. Zika Virus Infection Associated With Severe Thrombocytopenia.

    PubMed

    Sharp, Tyler M; Muñoz-Jordán, Jorge; Perez-Padilla, Janice; Bello-Pagán, Melissa I; Rivera, Aidsa; Pastula, Daniel M; Salinas, Jorge L; Martínez Mendez, Jose H; Méndez, Mónica; Powers, Ann M; Waterman, Stephen; Rivera-García, Brenda

    2016-11-01

    We report two patients that developed severe thrombocytopenia after Zika virus (ZIKV) infection. The first patient had 1000 platelets/μL and died after multiple hemorrhages. The second patient had 2000 platelets/μL, had melena and ecchymoses, and recovered after receiving intravenous immunoglobulin. ZIKV may be associated with immune-mediated severe thrombocytopenia.

  16. Infection of Plants by Tobacco Mosaic Virus.

    ERIC Educational Resources Information Center

    McDaniel, Larry; Maratos, Marina; Farabaugh, Joan

    1998-01-01

    Provides three exercises that introduce high school and college students to a common strain of the tobacco mosaic virus and the study of some basic biological processes. Activities involve inoculation of plants and observing and recording symptom development in infected plants. (DDR)

  17. Mental Status after West Nile Virus Infection

    PubMed Central

    Sadek, Joseph; Pergam, Steven; Echevarria, Leonor A.; Davis, Larry E.; Goade, Diane; Harnar, Joanne; Nofchissey, Robert A.; Sewel, C. Mack; Ettestad, Paul

    2006-01-01

    Mental status after acute West Nile virus infection has not been examined objectively. We compared Telephone Interview for Cognitive Status scores of 116 patients with West Nile fever or West Nile neuroinvasive disease. Mental status was poorer and cognitive complaints more frequent with West Nile neuroinvasive disease (p = 0.005). PMID:16965710

  18. The neurobiology of varicella zoster virus infection

    PubMed Central

    Gilden, D.; Mahalingam, R.; Nagel, M. A.; Pugazhenthi, S.; Cohrs, R. J.

    2011-01-01

    Varicella zoster virus (VZV) is a neurotropic herpesvirus that infects nearly all humans. Primary infection usually causes chickenpox (varicella), after which virus becomes latent in cranial nerve ganglia, dorsal root ganglia and autonomic ganglia along the entire neuraxis. Although VZV cannot be isolated from human ganglia, nucleic acid hybridization and, later, polymerase chain reaction proved that VZV is latent in ganglia. Declining VZV-specific host immunity decades after primary infection allows virus to reactivate spontaneously, resulting in shingles (zoster) characterized by pain and rash restricted to 1-3 dermatomes. Multiple other serious neurological and ocular disorders also result from VZV reactivation. This review summarizes the current state of knowledge of the clinical and pathological complications of neurological and ocular disease produced by VZV reactivation, molecular aspects of VZV latency, VZV virology and VZV-specific immunity, the role of apoptosis in VZV-induced cell death, and the development of an animal model provided by simian varicella virus infection of monkeys. PMID:21342215

  19. Uterine adenocarcinoma with feline leukemia virus infection.

    PubMed

    Cho, Sung-Jin; Lee, Hyun-A; Hong, Sunhwa; Kim, Okjin

    2011-12-01

    Feline endometrial adenocarcinomas are uncommon malignant neoplasms that have been poorly characterized to date. In this study, we describe a uterine adenocarcinoma in a Persian cat with feline leukemia virus infection. At the time of presentation, the cat, a female Persian chinchilla, was 2 years old. The cat underwent surgical ovariohystectomy. A cross-section of the uterine wall revealed a thickened uterine horn. The cat tested positive for feline leukemia virus as detected by polymerase chain reaction. Histopathological examination revealed uterine adenocarcinoma that had metastasized to the omentum, resulting in thickening and the formation of inflammatory lesions. Based on the histopathological findings, this case was diagnosed as a uterine adenocarcinoma with abdominal metastasis. To the best of our knowledge, this is the first report of a uterine adenocarcinoma with feline leukemia virus infection.

  20. Previous infection with a mesogenic strain of Newcastle disease virus affects infection with highly pathogenic avian influenza viruses in chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza virus (AIV) and Newcastle disease virus (NDV) are two of the most important viruses affecting poultry worldwide, but little is known on the interactions between these two viruses when infecting birds. In a previous study we found that infection of chickens with a mesogenic strain of...

  1. Immunobiology of Ebola and Lassa virus infections.

    PubMed

    Prescott, Joseph B; Marzi, Andrea; Safronetz, David; Robertson, Shelly J; Feldmann, Heinz; Best, Sonja M

    2017-03-01

    Two of the most important contemporary emerging viruses that affect human health in Africa are Ebola virus (EBOV) and Lassa virus (LASV). The 2013-2016 West African outbreak of EBOV was responsible for more than 11,000 deaths, primarily in Guinea, Sierra Leone and Liberia. LASV is constantly emerging in these and surrounding West African countries, with an estimate of more than 500,000 cases of Lassa fever, and approximately 5,000 deaths, annually. Both EBOV and LASV are zoonotic, and human infection often results in a severe haemorrhagic fever in both cases. However, the contribution of specific immune responses to disease differs between EBOV and LASV. This Review examines innate and adaptive immune responses to these viruses with the goal of delineating responses that are associated with protective versus pathogenic outcomes.

  2. Oral Manifestations of Human Immunodeficiency Virus Infection

    PubMed Central

    Epstein, Joel B.; Mathias, Richard G.

    1988-01-01

    The AIDS epidemic continues. All health-care workers, including physicians and dental personnel, may be instrumental in recognizing risk factors associated with Acquired Immunodeficiency Syndrome (AIDS) and Human Immunodeficiency Virus (HIV) infection. Oral signs and symptoms of HIV infection may be the first presentation of the disease or may develop during the course of the disease and require management. Knowledge of the signs, symptoms and associated infections and tumours is needed to assist in recognition, diagnosis, and treatment. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7Figure 8Figure 9Figure 10Figure 11Figure 12Figure 13 PMID:21253078

  3. Update on oral herpes virus infections.

    PubMed

    Balasubramaniam, Ramesh; Kuperstein, Arthur S; Stoopler, Eric T

    2014-04-01

    Oral herpes virus infections (OHVIs) are among the most common mucosal disorders encountered by oral health care providers. These infections can affect individuals at any age, from infants to the elderly, and may cause significant pain and dysfunction. Immunosuppressed patients may be at increased risk for serious and potential life-threatening complications caused by OHVIs. Clinicians may have difficulty in diagnosing these infections because they can mimic other conditions of the oral mucosa. This article provides oral health care providers with clinically relevant information regarding etiopathogenesis, diagnosis, and management of OHVIs.

  4. Human Respiratory Syncytial Virus: Infection and Pathology.

    PubMed

    Bohmwald, Karen; Espinoza, Janyra A; Rey-Jurado, Emma; Gómez, Roberto S; González, Pablo A; Bueno, Susan M; Riedel, Claudia A; Kalergis, Alexis M

    2016-08-01

    The human respiratory syncytial virus (hRSV) is by far the major cause of acute lower respiratory tract infections (ALRTIs) worldwide in infants and children younger than 2 years. The overwhelming number of hospitalizations due to hRSV-induced ALRTI each year is due, at least in part, to the lack of licensed vaccines against this virus. Thus, hRSV infection is considered a major public health problem and economic burden in most countries. The lung pathology developed in hRSV-infected individuals is characterized by an exacerbated proinflammatory and unbalanced Th2-type immune response. In addition to the adverse effects in airway tissues, hRSV infection can also cause neurologic manifestations in the host, such as seizures and encephalopathy. Although the origins of these extrapulmonary symptoms remain unclear, studies with patients suffering from neurological alterations suggest an involvement of the inflammatory response against hRSV. Furthermore, hRSV has evolved numerous mechanisms to modulate and evade the immune response in the host. Several studies have focused on elucidating the interactions between hRSV virulence factors and the host immune system, to rationally design new vaccines and therapies against this virus. Here, we discuss about the infection, pathology, and immune response triggered by hRSV in the host.

  5. Bacterial Respiratory Infections Complicating Human Immunodeficiency Virus.

    PubMed

    Feldman, Charles; Anderson, Ronald

    2016-04-01

    Opportunistic bacterial and fungal infections of the lower respiratory tract, most commonly those caused by Streptococcus pneumoniae (the pneumococcus), Mycobacterium tuberculosis, and Pneumocystis jirovecii, remain the major causes of mortality in those infected with human immunodeficiency virus (HIV). Bacterial respiratory pathogens most prevalent in those infected with HIV, other than M. tuberculosis, represent the primary focus of the current review with particular emphasis on the pneumococcus, the leading cause of mortality due to HIV infection in the developed world. Additional themes include (1) risk factors; (2) the predisposing effects of HIV-mediated suppression on pulmonary host defenses, possibly intensified by smoking; (3) clinical and laboratory diagnosis, encompassing assessment of disease severity and outcome; and (4) antibiotic therapy. The final section addresses current recommendations with respect to pneumococcal immunization in the context of HIV infection, including an overview of the rationale underpinning the current "prime-boost" immunization strategy based on sequential administration of pneumococcal conjugate vaccine 13 and pneumococcal polysaccharide vaccine 23.

  6. [Hepatitis C virus infection and alcohol].

    PubMed

    Campollo, Octavio

    2002-10-01

    It was thought that HCV infection was very frequent among alcoholics; some even though that this disease affected nearly 35% of this group. Now there seems to be a consensus among the main investigator groups that the correlation of hepatitis C and alcohol increases the risk of complications, cirrhosis and liver cancer included. Moreover, it's now certain that among patients with HCV infection, alcohol consumption increases the risk of death from live diseases during the first 10 years of the disease. Alcoholism is also considered a predisposing factor for HCV infection, but not for hepatitis B virus infection. Prospective studies about post-transfusional hepatitis C showed the risk of cirrhosis increases from 7.8 to 31.1 times if the patient consumed significant amounts of alcohol (> 80 g a day). One of the recommendations for every patient with HCV infection is to abstain from drinking alcohol.

  7. Farmyard pox: parapox virus infection in man.

    PubMed

    Shelley, W B; Shelley, E D

    1983-06-01

    Inasmuch as orf, milker's nodules and bovine papular stomatitis pox are clinically identical in man and are induced by currently indistinguishable parapox viruses, we propose a new generic term 'farmyard pox' for these diseases. This affords the clinician a diagnosis based on a common set of clinical and electron microscopic findings rather than one based on an uncertain or even misleading history. A case in point is reported in which the history failed to reveal a specific animal source of the virus, but electron microscopy confirmed the presence of parapox infection.

  8. Respiratory syncytial virus infection in cattle.

    PubMed

    Sacco, R E; McGill, J L; Pillatzki, A E; Palmer, M V; Ackermann, M R

    2014-03-01

    Bovine respiratory syncytial virus (RSV) is a cause of respiratory disease in cattle worldwide. It has an integral role in enzootic pneumonia in young dairy calves and summer pneumonia in nursing beef calves. Furthermore, bovine RSV infection can predispose calves to secondary bacterial infection by organisms such as Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni, resulting in bovine respiratory disease complex, the most prevalent cause of morbidity and mortality among feedlot cattle. Even in cases where animals do not succumb to bovine respiratory disease complex, there can be long-term losses in production performance. This includes reductions in feed efficiency and rate of gain in the feedlot, as well as reproductive performance, milk production, and longevity in the breeding herd. As a result, economic costs to the cattle industry from bovine respiratory disease have been estimated to approach $1 billion annually due to death losses, reduced performance, and costs of vaccinations and treatment modalities. Human and bovine RSV are closely related viruses with similarities in histopathologic lesions and mechanisms of immune modulation induced following infection. Therefore, where appropriate, we provide comparisons between RSV infections in humans and cattle. This review article discusses key aspects of RSV infection of cattle, including epidemiology and strain variability, clinical signs and diagnosis, experimental infection, gross and microscopic lesions, innate and adaptive immune responses, and vaccination strategies.

  9. Changing clinical scenario in Chandipura virus infection

    PubMed Central

    Sudeep, A.B.; Gurav, Y.K.; Bondre, V.P.

    2016-01-01

    Chandipura virus (CHPV) (Vesiculovirus: Rhabdoviridae) garnered global attention as an emerging neurotropic pathogen inflicting high mortality in children within 24 h of commencement of symptoms. The 2003-2004 outbreaks in Central India witnessed case fatality rates ranging from 56-75 per cent in Andhra Pradesh and Gujarat with typical encephalitic symptoms. Due to the acute sickness and rapid deterioration, the precise mechanism of action of the virus is still unknown. Recent studies have shown increased expression of CHPV phosphoprotein upto 6 h post infection (PI) demonstrating CHPV replication in neuronal cells and the rapid destruction of the cells by apoptosis shed light on the probable mechanism of rapid death in children. Phlebotomine sandflies are implicated as vectors due to their predominance in endemic areas, repeated virus isolations and their ability to transmit the virus by transovarial and venereal routes. Significant contributions have been made in the development of diagnostics and prophylactics, vaccines and antivirals. Two candidate vaccines, viz. a recombinant vaccine and a killed vaccine and siRNAs targeting P and M proteins have been developed and are awaiting clinical trials. Rhabdomyosarcoma and Phlebotomus papatasi cell lines as well as embryonated chicken eggs have been found useful in virus isolation and propagation. Despite these advancements, CHPV has been a major concern in Central India and warrants immediate attention from virologists, neurologists, paediatricians and the government for containing the virus. PMID:27748295

  10. Estimating infectivity rates and attack windows for two viruses.

    PubMed

    Zhang, J; Noe, D A; Wu, J; Bailer, A J; Wright, S E

    2012-12-01

    Cells exist in an environment in which they are simultaneously exposed to a number of viral challenges. In some cases, infection by one virus may preclude infection by other viruses. Under the assumption of independent times until infection by two viruses, a procedure is presented to estimate the infectivity rates along with the time window during which a cell might be susceptible to infection by multiple viruses. A test for equal infectivity rates is proposed and interval estimates of parameters are derived. Additional hypothesis tests of potential interest are also presented. The operating characteristics of these tests and the estimation procedure are explored in simulation studies.

  11. Psoralen inactivation of influenza and herpes simplex viruses and of virus-infected cells.

    PubMed Central

    Redfield, D C; Richman, D D; Oxman, M N; Kronenberg, L H

    1981-01-01

    Psoralen compounds covalently bind to nucleic acids when irradiated with long-wavelength ultraviolet light. This treatment can destroy the infectivity of deoxyribonucleic acid and ribonucleic acid viruses. Two psoralen compounds, 4'-hydroxymethyltrioxsalen and 4'-aminomethyltrioxsalen, were used with long-wavelength ultraviolet light to inactivate cell-free herpes simplex and influenza viruses and to render virus-infected cells noninfectious. This method of inactivation was compared with germicidal (short-wavelength) ultraviolet light irradiation. The antigenicity of the treated, virus-infected, antigen-bearing cells was examined by immunofluorescence and radioimmunoassay and by measuring the capacity of the herpes simplex virus-infected cells to stimulate virus-specific lymphocyte proliferation. The infectivity of the virus-infected cells could be totally eliminated without altering their viral antigenicity. The use of psoralen plus long-wavelength ultraviolet light is well suited to the preparation of noninfectious virus antigens and virus antigen-bearing cells for immunological assays. PMID:6265375

  12. Psoralen inactivation of influenza and herpes simplex viruses and of virus-infected cells

    SciTech Connect

    Redfield, D.C.; Richman, D.D.; Oxman, M.N.; Kronenberg, L.H.

    1981-06-01

    Psoralen compounds covalently bind to nucleic acids when irradiated with long-wavelength ultraviolet light. This treatment can destroy the infectivity of deoxyribonucleic acid and ribonucleic acid viruses. Two psoralen compounds, 4'-hydroxymethyltrioxsalen and 4'-aminomethyltrioxsalen, were used with long-wavelength ultraviolet light to inactivate cell-free herpes simplex and influenza viruses and to render virus-infected cells noninfectious. This method of inactivation was compared with germicidal (short-wavelength) ultraviolet light irradiation. The antigenicity of the treated, virus-infected, antigen-bearing cells was examined by immunofluorescence and radioimmunoassay and by measuring the capacity of the herpes simplex virus-infected cells to stimulate virus-specific lymphocyte proliferation. The infectivity of the virus-infected cells could be totally eliminated without altering their viral antigenicity. The use of psoralen plus long-wavelength ultraviolet light is well suited to the preparation of noninfectious virus antigens and virus antigen-bearing cells for immunological assays.

  13. A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Virus-host interactions drive a remarkable diversity of immune responses and countermeasures. While investigating virus-invertebrate host interactions we found that two RNA viruses with broad host ranges, vesicular stomatitis virus (VSV) and Sindbis virus (SINV), were unable to infect certain Lepido...

  14. Human papilloma virus infection and psoriasis: Did human papilloma virus infection trigger psoriasis?

    PubMed Central

    Jain, Sonia P.; Gulhane, Sachin; Pandey, Neha; Bisne, Esha

    2015-01-01

    Psoriasis is an autoimmune chronic inflammatory skin disease known to be triggered by streptococcal and HIV infections. However, human papilloma virus infection (HPV) as a triggering factor for the development of psoriasis has not been reported yet. We, hereby report a case of plaque type with inverse psoriasis which probably could have been triggered by genital warts (HPV infection) and discuss the possible pathomechanisms for their coexistence and its management. PMID:26692619

  15. Myeloradiculopathy associated with chikungunya virus infection.

    PubMed

    Bank, Anna M; Batra, Ayush; Colorado, Rene A; Lyons, Jennifer L

    2016-02-01

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that is endemic to parts of Africa, South and Southeast Asia, and more recently the Caribbean. Patients typically present with fever, rash, and arthralgias, though neurologic symptoms, primarily encephalitis, have been described. We report the case of a 47-year-old woman who was clinically diagnosed with CHIKV while traveling in the Dominican Republic and presented 10 days later with left lower extremity weakness, a corresponding enhancing thoracic spinal cord lesion, and positive CHIKV serologies. She initially responded to corticosteroids, followed by relapsing symptoms and gradual clinical improvement. The time lapse between acute CHIKV infection and the onset of myelopathic sequelae suggests an immune-mediated phenomenon rather than direct activity of the virus itself. Chikungunya virus should be considered in the differential diagnosis of myelopathy in endemic areas. The progression of symptoms despite corticosteroid administration suggests more aggressive immunomodulatory therapies may be warranted at disease onset.

  16. Pathogenesis of hepatitis C virus infection.

    PubMed

    Kohla, M; Bonacini, M

    2006-06-01

    The hepatitis C virus (HCV) is a single stranded RNA virus. In 60-80% of patients, it is able to escape innate and adaptive immune surveillance. Thus it establishes itself as an agent of chronic hepatitis. Cytotoxic lymphocytes then contribute to liver injury in an attempt to eradicate the virus. On the other hand, strong multispecific T-lymphocyte reaction against HCV proteins is associated with viral clearance. Both CD4+ and CD8+ lymphocyte functions are important to effect this outcome. In chronic infection, genetic and environmental factors determine the progression of inflammation and fibrosis in individual patients. Of these factors, age, gender, race and alcohol use are the most established ones. The development of hepatocellular carcinoma is mainly restricted to patients with cirrhosis.

  17. [A NEW PANDEMIC: ZIKA VIRUS INFECTION].

    PubMed

    Bourée, Patrice

    2016-06-01

    Zika virus is a flavivirus isolated in non human primates in 1647, then in humans 1954 (Uganda). It emerged on Micronesia (island af Yap) in 2007, then in French Polynesia in 2013-2014, in South America (mostly in Brazil and Colombia) in 2015 and in French West Indies in 2016. It is transmitted by the bite of Aedes mosquitoes. Zika virus infection is symptomatic in only 20% of cases and clinical presentation is associated with mild illness. But several neurological complications are reported (as Guillain-Barré syndrome: 48 cases in French Polynesia) and congenital malformations (microcephaly). Laboratory diagnosis is based on virus isolation by PCR. There is no specific treatment or vaccine available against the Zika virs. Prevention is based on measures of protection from mosquitoes bites.

  18. Sexual transmission of hepatitis C virus infection

    PubMed Central

    Rooney, G.; Gilson, R. J.

    1998-01-01

    BACKGROUND: Hepatitis C virus (HCV) is the cause of almost all cases of parenterally transmitted non-A, non-B viral hepatitis (NANBH). HCV is an RNA virus, unrelated to the hepatitis viruses, A, B, D, or E; it was first identified in 1989. Although most infections become chronic, and it may lead to chronic liver disease, most patients with HCV infection are asymptomatic. The predominant modes of transmission are by blood, blood products, or other parenteral exposure, particularly injecting drug use. More contentious is the role of sexual transmission, although evidence for this was provided by studies of NANBH. OBJECTIVE: This review considers the evidence for sexual transmission, and the types of studies used to estimate the rate of transmission and the factors that may influence it. METHOD: A Medline search using the keywords hepatitis C, sex, transmission, and prevalence in MeSH and free text. References in papers were searched, and some unpublished data identified. References were further selected to illustrate different methodologies. FINDINGS: Evidence for sexual transmission is provided by several types of study including prevalence studies in groups at risk of other STDs, investigation of cases identified from surveillance reports, and cross sectional and longitudinal partner studies. Many studies are limited by their small size, the sensitivity and specificity of early assays, lack of controls, or the difficulty of excluding other routes of transmission. One prospective cohort study reported an incidence of 12 per 1000 person years in the sexual partners of HCV infected patients. 1-3% of partners of HCV infected patients are found to be infected in cross sectional studies. Co-infection with HIV, duration of the relationship, or chronic liver disease may be independent cofactors increasing the risk of transmission. A meta-analysis of selected studies may be informative, and further larger prospective studies are required. There is a small but definite risk

  19. Treatment of hepatitis C virus infection

    PubMed Central

    Weigand, Kilian; Stremmel, Wolfgang; Encke, Jens

    2007-01-01

    Acute and chronic hepatitis C virus (HCV) infection remains a serious health problem worldwide, however, there has been advancement in the treatment of HCV infection due to standard treatment using pegylated interferon and ribavirin. The literature indicates that therapy for HCV is becoming more individualized. In addition to considering genotype and viral RNA levels before treatment, achievement of an early virologic response (EVR) and a rapid virologic response (RVR) is now possible during therapy. Moreover, problem patients, such as non-responders, relapsers, HIV or HBV co-infected patients, patients with liver cirrhosis, and pre- or post-liver transplantation patients are an increasing fraction of the patients requiring treatment. This article reviews the literature regarding standard treatments and problem patients with acute and chronic HCV infection. It also includes discussion on contraindications and side effects of treatment with interferon and ribavirin, as well as new drug development. PMID:17461488

  20. Epidemiology of hepatitis C virus infection

    PubMed Central

    Alter, Miriam J

    2007-01-01

    Globally, hepatitis C virus (HCV) has infected an estimated 130 million people, most of whom are chronically infected. HCV-infected people serve as a reservoir for transmission to others and are at risk for developing chronic liver disease, cirrhosis, and primary hepatocellular carcinoma (HCC). It has been estimated that HCV accounts for 27% of cirrhosis and 25% of HCC worldwide. HCV infection has likely been endemic in many populations for centuries. However, the wave of increased HCV-related morbidity and mortality that we are now facing is the result of an unprecedented increase in the spread of HCV during the 20th century. Two 20th century events appear to be responsible for this increase; the widespread availability of injectable therapies and the illicit use of injectable drugs. PMID:17552026

  1. Determine the Infectivity of Neurotropic Viruses by the Oral Route.

    DTIC Science & Technology

    Four street strains of rabiesvirus were tested for their ability to infect weanling mice via the oral route. Two strains isolated from vampire bats ...brown fat of a naturally infected insectivorous bat did not induce rabies in mice fed infected brain tissue. Attempts were made to induce oral...virus was also studied. A strain of SLE virus isolated from the blood of a naturally infected bat produced encephalitis in mice fed virus laden brain tissue. (Author)

  2. Epidemiology of hepatitis C virus infection.

    PubMed

    Bellentani, S; Miglioli, L; Bedogni, G; Crocè, L S; Tiribelli, C

    2005-03-01

    Although a lot of novel information and data on the epidemiology of hepatitis C virus (HCV) infection are available worldwide, the majority of these information are often fragmentary and sometimes contradictory. This review tries to highlight all the data available on the prevalence (i.e. the number of cases present in a known population), the risk factors, the natural history and the incidence (i.e. the number of new cases that occur every year) of HCV infection in the world, and particularly in Italy.

  3. Diagnostic tools for Toscana virus infection.

    PubMed

    Cusi, Maria Grazia; Savellini, Gianni Gori

    2011-07-01

    Toscana virus (TOSV; Phlebovirus, Bunyaviridae) is an important etiological agent of acute meningitis and meningoencephalitis in Mediterranean countries. Laboratory diagnosis has been carried out in serological studies using ELISA, immunofluorescence and/or neutralization tests that are not influenced by the virus viability; however, in the acute phase of the infection, nucleic acid amplification techniques are the methods of choice to diagnose viral meningitis from cerebrospinal fluid samples. Molecular methods are rapid and sensitive and, unlike traditional methods, such as virus isolation by cell culture, they are not influenced by the viability of the virus in the clinical specimen; however, the RNA integrity is crucial for the success of these methods. Real-time PCR is the most important molecular method used in laboratories worldwide, since it is less time-consuming and it reduces the risk of contamination. Therefore, a sensitive real-time PCR has been developed for diagnosis of suspected cases of TOSV infection either autochthonous and/or imported, since a new lineage of TOSV, divergent from the Italian prototype, has recently been reported in Spain.

  4. Chaperones in hepatitis C virus infection

    PubMed Central

    Khachatoorian, Ronik; French, Samuel W

    2016-01-01

    The hepatitis C virus (HCV) infects approximately 3% of the world population or more than 185 million people worldwide. Each year, an estimated 350000-500000 deaths occur worldwide due to HCV-associated diseases including cirrhosis and hepatocellular carcinoma. HCV is the most common indication for liver transplantation in patients with cirrhosis worldwide. HCV is an enveloped RNA virus classified in the genus Hepacivirus in the Flaviviridae family. The HCV viral life cycle in a cell can be divided into six phases: (1) binding and internalization; (2) cytoplasmic release and uncoating; (3) viral polyprotein translation and processing; (4) RNA genome replication; (5) encapsidation (packaging) and assembly; and (6) virus morphogenesis (maturation) and secretion. Many host factors are involved in the HCV life cycle. Chaperones are an important group of host cytoprotective molecules that coordinate numerous cellular processes including protein folding, multimeric protein assembly, protein trafficking, and protein degradation. All phases of the viral life cycle require chaperone activity and the interaction of viral proteins with chaperones. This review will present our current knowledge and understanding of the role of chaperones in the HCV life cycle. Analysis of chaperones in HCV infection will provide further insights into viral/host interactions and potential therapeutic targets for both HCV and other viruses. PMID:26783419

  5. Mechanisms of Zika Virus Infection and Neuropathogenesis.

    PubMed

    Olagnier, David; Muscolini, Michela; Coyne, Carolyn B; Diamond, Michael S; Hiscott, John

    2016-08-01

    A spotlight has been focused on the mosquito-borne Zika virus (ZIKV) because of its epidemic outbreak in Brazil and Latin America, as well as the severe neurological manifestations of microcephaly and Guillain-Barré syndrome associated with infection. In this review, we discuss the recent literature on ZIKV-host interactions, including new mechanistic insight concerning the basis of ZIKV-induced neuropathogenesis.

  6. Influenza A virus infections in swine: pathogenesis and diagnosis.

    PubMed

    Janke, B H

    2014-03-01

    Influenza has been recognized as a respiratory disease in swine since its first appearance concurrent with the 1918 "Spanish flu" human pandemic. All influenza viruses of significance in swine are type A, subtype H1N1, H1N2, or H3N2 viruses. Influenza viruses infect epithelial cells lining the surface of the respiratory tract, inducing prominent necrotizing bronchitis and bronchiolitis and variable interstitial pneumonia. Cell death is due to direct virus infection and to insult directed by leukocytes and cytokines of the innate immune system. The most virulent viruses consistently express the following characteristics of infection: (1) higher or more prolonged virus replication, (2) excessive cytokine induction, and (3) replication in the lower respiratory tract. Nearly all the viral proteins contribute to virulence. Pigs are susceptible to infection with both human and avian viruses, which often results in gene reassortment between these viruses and endemic swine viruses. The receptors on the epithelial cells lining the respiratory tract are major determinants of infection by influenza viruses from other hosts. The polymerases, especially PB2, also influence cross-species infection. Methods of diagnosis and characterization of influenza viruses that infect swine have improved over the years, driven both by the availability of new technologies and by the necessity of keeping up with changes in the virus. Testing of oral fluids from pigs for virus and antibody is a recent development that allows efficient sampling of large numbers of animals.

  7. Development of therapeutics for treatment of Ebola virus infection.

    PubMed

    Li, Haoyang; Ying, Tianlei; Yu, Fei; Lu, Lu; Jiang, Shibo

    2015-02-01

    Ebola virus infection can cause Ebola virus disease (EVD). Patients usually show severe symptoms, and the fatality rate can reach up to 90%. No licensed medicine is available. In this review, development of therapeutics for treatment of Ebola virus infection and EVD will be discussed.

  8. Vaccinia virus infections in martial arts gym, Maryland, USA, 2008.

    PubMed

    Hughes, Christine M; Blythe, David; Li, Yu; Reddy, Ramani; Jordan, Carol; Edwards, Cindy; Adams, Celia; Conners, Holly; Rasa, Catherine; Wilby, Sue; Russell, Jamaal; Russo, Kelly S; Somsel, Patricia; Wiedbrauk, Danny L; Dougherty, Cindy; Allen, Christopher; Frace, Mike; Emerson, Ginny; Olson, Victoria A; Smith, Scott K; Braden, Zachary; Abel, Jason; Davidson, Whitni; Reynolds, Mary; Damon, Inger K

    2011-04-01

    Vaccinia virus is an orthopoxvirus used in the live vaccine against smallpox. Vaccinia virus infections can be transmissible and can cause severe complications in those with weakened immune systems. We report on a cluster of 4 cases of vaccinia virus infection in Maryland, USA, likely acquired at a martial arts gym.

  9. Clinical and biological differences between recurrent herpes simplex virus and varicella-zoster virus infections

    SciTech Connect

    Straus, S.E. )

    1989-12-01

    The major features that distinguish recurrent herpes simplex virus infections from zoster are illustrated in this article by two case histories. The clinical and epidemiologic features that characterize recurrent herpes simplex virus and varicella-zoster virus infections are reviewed. It is noted that herpesvirus infections are more common and severe in patients with cellular immune deficiency. Each virus evokes both humoral and cellular immune response in the course of primary infection. DNA hybridization studies with RNA probes labelled with sulfur-35 indicate that herpes simplex viruses persist within neurons, and that varicella-zoster virus is found in the satellite cells that encircle the neurons.

  10. Human immunodeficiency virus, herpes virus infections, and pulmonary vascular disease

    PubMed Central

    Flores, Sonia C.; Almodovar, Sharilyn

    2013-01-01

    The following state-of-the-art seminar was delivered as part of the Aspen Lung Conference on Pulmonary Hypertension and Vascular Diseases held in Aspen, Colorado in June 2012. This paper will summarize the lecture and present results from a nonhuman primate model of infection with Simian (Human) Immunodeficiency Virus - nef chimeric virions as well as the idea that polymorphisms in the HIV-1 nef gene may be driving the immune response that results in exuberant inflammation and aberrant endothelial cell (EC) function. We will present data gathered from primary HIV nef isolates where we tested the biological consequences of these polymorphisms and how their presence in human populations may predict patients at risk for developing this disease. In this article, we also discuss how a dysregulated immune system, in conjunction with a viral infection, could contribute to pulmonary arterial hypertension (PAH). Both autoimmune diseases and some viruses are associated with defects in the immune system, primarily in the function of regulatory T cells. These T-cell defects may be a common pathway in the formation of plexiform lesions. Regardless of the route by which viruses may lead to PAH, it is important to recognize their role in this rare disease. PMID:23662195

  11. Methods for assessing feline immunodeficiency virus infection, infectivity and purification.

    PubMed

    Ammersbach, Melanie; Bienzle, Dorothee

    2011-10-15

    Infection of cats with the feline immunodeficiency virus (FIV) recapitulates many aspects of infection of humans with HIV, including highly activated but ineffectual immune responses. Infected hosts remain seropositive for life, and detection of antibodies is the mainstay of diagnosis. However, to quantify virus for research or prognosis, viral proteins, nucleic acids or enzymes, are typically measured by ELISA, PCR or activity, respectively. While such assays are in wide use, they do not distinguish whole, infectious viral particles from defective or disrupted viruses. Titers of infectious viral particles may be estimated from tissue culture infectious doses or by enumerating cell-associated viral proteins, viral transcriptional activity or formation of syncytia. To analyze the viral proteome and the incorporation of host components into viral envelopes, pure lentiviral preparations are required. Methods for purifying lentiviruses include ultracentrifugation to separate particles by size, mass and/or density; chromatography to separate particles by charge, affinity or size; and additional removal of extraviral proteins and exosomes through subtilisin digestion or immunoaffinity. This article reviews advantages and disadvantages of different approaches to purification of lentiviruses with special reference to suitability for FIV, and highlights effects of purification on immune responses and immune assays.

  12. West Nile Virus: Biology, Transmission, and Human Infection

    PubMed Central

    Colpitts, Tonya M.; Conway, Michael J.; Montgomery, Ruth R.

    2012-01-01

    Summary: West Nile Virus was introduced into the Western Hemisphere during the late summer of 1999 and has been causing significant and sometimes severe human diseases since that time. This article briefly touches upon the biology of the virus and provides a comprehensive review regarding recent discoveries about virus transmission, virus acquisition, and human infection and disease. PMID:23034323

  13. Orthopox virus infections in Eurasian wild rodents.

    PubMed

    Kinnunen, Paula M; Henttonen, Heikki; Hoffmann, Bernd; Kallio, Eva R; Korthase, Christian; Laakkonen, Juha; Niemimaa, Jukka; Palva, Airi; Schlegel, Mathias; Ali, Hanan Sheikh; Suominen, Paula; Ulrich, Rainer G; Vaheri, Antti; Vapalahti, Olli

    2011-08-01

    The genus Orthopoxvirus includes variola (smallpox) virus and zoonotic cowpox virus (CPXV). All orthopoxviruses (OPV) are serologically cross-reactive and cross-protective, and after the cessation of smallpox vaccination, CPXV and other OPV infections represent an emerging threat to human health. In this respect CPXV, with its reservoir in asymptomatically infected wild rodents, is of special importance. In Europe, clinical cowpox has been diagnosed in both humans and animals. The main objective of this study was to elucidate the prevalence of OPV infections in wild rodents in different parts of Eurasia and to compare the performance of three real-time polymerase chain reaction (PCR) methods in detecting OPV DNA in wildlife samples. We investigated 962 wild rodents from Northern Europe (Finland), Central Europe (Germany), and Northern Asia (Siberia, Russia) for the presence of OPV antibodies. According to a CPXV antigen-based immunofluorescence assay, animals from 13 of the 17 locations (76%) showed antibodies. Mean seroprevalence was 33% in Finland (variation between locations 0%-69%), 32% in Germany (0%-43%), and 3.2% (0%-15%) in Siberia. We further screened tissue samples from 513 of the rodents for OPV DNA using up to three real-time PCRs. Three rodents from two German and one Finnish location were OPV DNA positive. The amplicons were 96% to 100% identical to available CPXV sequences. Further, we demonstrated OPV infections as far east as the Baikal region and occurring in hamster and two other rodent species, ones previously unnoticed as possible reservoir hosts. Based on serological and PCR findings, Eurasian wild rodents are frequently but nonpersistently infected with OPVs. Results from three real-time PCR methods were highly concordant. This study extends the geographic range and wildlife species diversity in which OPV (or CPXV) viruses are naturally circulating.

  14. Human Jamestown canyon virus infection --- Montana, 2009.

    PubMed

    2011-05-27

    Jamestown Canyon virus (JCV) is a mosquito-borne zoonotic pathogen belonging to the California serogroup of bunyaviruses. Although JCV is widely distributed throughout temperate North America, reports of human JCV infection in the United States are rare. This is the first report of human JCV infection detected in Montana, one of only 15 cases reported in the United States since 2004, when JCV became reportable. On May 26, 2009, a man aged 51 years with no travel history outside of Montana went to a local emergency department immediately following onset of fever, severe frontal headache, dizziness, left-sided numbness, and tingling. His blood pressure was elevated. Stroke was ruled out, oxygen was administered, medication was prescribed for hypertension, and the patient was sent home. One week later, the patient visited his primary-care physician complaining of continued neurologic symptoms consistent with acute febrile encephalitis and recent mosquito bites. Although West Nile virus (WNV) disease was diagnosed based on detection of WNV-immunoglobulin M (IgM) and G (IgG) antibodies, subsequent testing indicated that the WNV antibodies were from a past infection and that his illness was caused by JCV. The final diagnosis of JCV infection was based on positive JCV-specific IgM enzyme-linked immunosorbent assay (ELISA) results and a fourfold rise in paired sample JCV plaque reduction neutralization test (PRNT) titers. This finding represents a previously unrecognized risk for JCV infection in Montana; clinicians should consider JCV infection when assessing patients for suspected arboviral infections.

  15. Avian influenza virus infections in humans.

    PubMed

    Wong, Samson S Y; Yuen, Kwok-Yung

    2006-01-01

    Seroepidemiologic and virologic studies since 1889 suggested that human influenza pandemics were caused by H1, H2, and H3 subtypes of influenza A viruses. If not for the 1997 avian A/H5N1 outbreak in Hong Kong of China, subtype H2 is the likely candidate for the next pandemic. However, unlike previous poultry outbreaks of highly pathogenic avian influenza due to H5 that were controlled by depopulation with or without vaccination, the presently circulating A/H5N1 genotype Z virus has since been spreading from Southern China to other parts of the world. Migratory birds and, less likely, bird trafficking are believed to be globalizing the avian influenza A/H5N1 epidemic in poultry. More than 200 human cases of avian influenza virus infection due to A/H5, A/H7, and A/H9 subtypes mainly as a result of poultry-to-human transmission have been reported with a > 50% case fatality rate for A/H5N1 infections. A mutant or reassortant virus capable of efficient human-to-human transmission could trigger another influenza pandemic. The recent isolation of this virus in extrapulmonary sites of human diseases suggests that the high fatality of this infection may be more than just the result of a cytokine storm triggered by the pulmonary disease. The emergence of resistance to adamantanes (amantadine and rimantadine) and recently oseltamivir while H5N1 vaccines are still at the developmental stage of phase I clinical trial are causes for grave concern. Moreover, the to-be pandemic strain may have little cross immunogenicity to the presently tested vaccine strain. The relative importance and usefulness of airborne, droplet, or contact precautions in infection control are still uncertain. Laboratory-acquired avian influenza H7N7 has been reported, and the laboratory strains of human influenza H2N2 could also be the cause of another pandemic. The control of this impending disaster requires more research in addition to national and international preparedness at various levels. The

  16. Management of hepatitis B virus infection.

    PubMed

    Lee, Haeok; Park, Wanju; Yang, Jin Hyang; You, Kwang Soo

    2010-01-01

    An estimated 2 million people are living with chronic hepatitis B virus (CHBV) in the United States and are at risk for long-term consequences such as cirrhosis, liver decompensation, and hepatocellular carcinoma. Less than 10 years ago, there was no treatment of CHBV infection, but now, new drugs have recently been approved and there is considerable new knowledge about the treatment of CHBV infection. Recently, consensus guidelines for the management of hepatitis B virus infection have been released by the National Institutes of Health and the American Medical Association, addressing the selection of patients and drugs for treatments. Determining what constitutes best practices to manage patients with CHBV is challenging and requires nurses and nurse practitioners to acquire and maintain up-to-date knowledge to understand recently approved drugs and disease management. Nurses and nurse practitioners should know how to identify patients who need treatment and how to educate, counsel, and monitor treatment adherence and side effects; these skills are crucially important. The goal of this article is to provide nurses with the most current consensus guidelines for the management of CHBV infection and their application in nursing practice to optimize treatment to enhance patient outcomes.

  17. Activity of andrographolide against chikungunya virus infection

    PubMed Central

    Wintachai, Phitchayapak; Kaur, Parveen; Lee, Regina Ching Hua; Ramphan, Suwipa; Kuadkitkan, Atichat; Wikan, Nitwara; Ubol, Sukathida; Roytrakul, Sittiruk; Chu, Justin Jang Hann; Smith, Duncan R.

    2015-01-01

    Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus that has recently engendered large epidemics around the world. There is no specific antiviral for treatment of patients infected with CHIKV, and development of compounds with significant anti-CHIKV activity that can be further developed to a practical therapy is urgently required. Andrographolide is derived from Andrographis paniculata, a herb traditionally used to treat a number of conditions including infections. This study sought to determine the potential of andrographolide as an inhibitor of CHIKV infection. Andrographolide showed good inhibition of CHIKV infection and reduced virus production by approximately 3log10 with a 50% effective concentration (EC50) of 77 μM without cytotoxicity. Time-of-addition and RNA transfection studies showed that andrographolide affected CHIKV replication and the activity of andrographolide was shown to be cell type independent. This study suggests that andrographolide has the potential to be developed further as an anti-CHIKV therapeutic agent. PMID:26384169

  18. Respiratory Syncytial Virus Infection (RSV): Transmission and Prevention

    MedlinePlus

    ... CDC Cancel Submit Search The CDC Respiratory Syncytial Virus Infection (RSV) Note: Javascript is disabled or is ... if you touch a surface that has the virus on it, like a doorknob, and then touch ...

  19. KINETIC PROFILE OF INFLUENZA VIRUS INFECTION IN THREE RAT STRAINS

    EPA Science Inventory

    Abstract

    Influenza infection is a respiratory disease of viral origin that can cause major epidemics in man. The influenza virus infects and damages epithelial cells of the respiratory tract and causes pneumonia. Lung lesions of mice infected with influenza virus resembl...

  20. [Microbiological diagnosis of human papilloma virus infection].

    PubMed

    Mateos-Lindemann, Maria Luisa; Pérez-Castro, Sonia; Rodríguez-Iglesias, Manuel; Pérez-Gracia, Maria Teresa

    2016-06-25

    Infection with human papillomavirus (HPV) is the leading cause of sexually transmitted infection worldwide. This virus generally causes benign lesions, such as genital warts, but persistent infection may lead to cervical cancer, anal cancer, vaginal cancer, and oropharyngeal cancer, although less frequently. Cervical cancer is a severe disease with a high mortality in some countries. Screening with cytology has been very successful in the last few years, but nowadays there are numerous studies that confirm that cytology should be replaced with the detection of HPV as a first line test in population based screening. There are several commercially available FDA approved tests for screening of cervical cancer. A new strategy, based on individual detection of the high risk genotypes HPV16 and HPV18, present in 70% of cervical cancer biopsies, has been proposed by some experts, and is going to be implemented in most countries in the future.

  1. Hepatitis B virus infection in immigrant populations

    PubMed Central

    Coppola, Nicola; Alessio, Loredana; Pisaturo, Mariantonietta; Macera, Margherita; Sagnelli, Caterina; Zampino, Rosa; Sagnelli, Evangelista

    2015-01-01

    Hepatitis B virus (HBV) is the most common cause of hepatitis worldwide, with nearly 350 million people chronically infected and 600000 deaths per year due to acute liver failure occurring during acute hepatitis or, more frequently, in HBV-related liver cirrhosis or hepatocellular carcinoma. Ongoing immigration from countries with a high HBV endemicity to those with a low HBV endemicity warrants particular attention to prevent the spread of HBV infection to the native population. This review article analyzes the epidemiology and virological and clinical characteristics of HBV infection in immigrant populations and in their host countries, and suggests prophylactic measures to prevent the spread of this infection. Among the immigrants from different geographical areas, those from South East Asia and sub-Saharan Africa show the highest prevalences of hepatitis B surface antigen (HBsAg) carriers, in accordance with the high endemicity of the countries of origin. The molecular characteristics of HBV infection in immigrants reflect those of the geographical areas of origin: HBV genotype A and D predominate in immigrants from Eastern Europe, B and C in those from Asia and genotype E in those from Africa. The literature data on the clinical course and treatment of HBsAg-positive immigrants are scanty. The management of HBV infection in immigrant populations is difficult and requires expert personnel and dedicated structures for their assistance. The social services, voluntary operators and cultural mediators are essential to achieve optimized psychological and clinical intervention. PMID:26730274

  2. Herpes virus infection of the peripheral nervous system.

    PubMed

    Steiner, Israel

    2013-01-01

    Among the human herpes viruses, three are neurotropic and capable of producing severe neurological abnormalities: herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) and varicella-zoster virus (VZV). Both the acute, primary infection and the reactivation from the site of latent infection, the dorsal sensory ganglia, are associated with severe human morbidity and mortality. The peripheral nervous system is one of the major loci affected by these viruses. The present review details the virology and molecular biology underlying the human infection. This is followed by detailed description of the symtomatology, clinical presentation, diagnosis, course, therapy, and prognosis of disorders of the peripheral nervous system caused by these viruses.

  3. Laboratory Evaluation of Infants with Possible Congenital Zika Virus Infection.

    PubMed

    Bell, Susan Givens

    2017-03-01

    Our understanding of the effects of maternal Zika virus infection on the newborn continues to evolve. First discovered in 1947 in the Zika Forest in Uganda, the world became more aware of the virus in 2015, with reports of hundreds of cases of microcephaly in Brazilian newborns whose mothers reported symptoms related to Zika viral infection during pregnancy. This article reviews the current guidelines for laboratory evaluation of newborns with possible congenital Zika virus infection.

  4. Acute Human Inkoo and Chatanga Virus Infections, Finland.

    PubMed

    Putkuri, Niina; Kantele, Anu; Levanov, Lev; Kivistö, Ilkka; Brummer-Korvenkontio, Markus; Vaheri, Antti; Vapalahti, Olli

    2016-05-01

    Inkoo virus (INKV) and Chatanga virus (CHATV), which are circulating in Finland, are mosquitoborne California serogroup orthobunyaviruses that have a high seroprevalence among humans. Worldwide, INKV infection has been poorly described, and CHATV infection has been unknown. Using serum samples collected in Finland from 7,961 patients suspected of having viral neurologic disease or Puumala virus infection during the summers of 2001-2013, we analyzed the samples to detect California serogroup infections. IgM seropositivity revealed 17 acute infections, and cross-neutralization tests confirmed presence of INKV or CHATV infections. All children (<16 years of age) with INKV infection were hospitalized; adults were outpatients with mild disease, except for 1 who was hospitalized with CHATV infection. Symptoms included fever, influenza-like illness, nausea or vomiting, disorientation, nuchal rigidity, headache, drowsiness, and seizures. Although many INKV and CHATV infections appear to be subclinical, these viruses can cause more severe disease, especially in children.

  5. Acute Human Inkoo and Chatanga Virus Infections, Finland

    PubMed Central

    Kantele, Anu; Levanov, Lev; Kivistö, Ilkka; Brummer-Korvenkontio, Markus; Vaheri, Antti; Vapalahti, Olli

    2016-01-01

    Inkoo virus (INKV) and Chatanga virus (CHATV), which are circulating in Finland, are mosquitoborne California serogroup orthobunyaviruses that have a high seroprevalence among humans. Worldwide, INKV infection has been poorly described, and CHATV infection has been unknown. Using serum samples collected in Finland from 7,961 patients suspected of having viral neurologic disease or Puumala virus infection during the summers of 2001–2013, we analyzed the samples to detect California serogroup infections. IgM seropositivity revealed 17 acute infections, and cross-neutralization tests confirmed presence of INKV or CHATV infections. All children (<16 years of age) with INKV infection were hospitalized; adults were outpatients with mild disease, except for 1 who was hospitalized with CHATV infection. Symptoms included fever, influenza-like illness, nausea or vomiting, disorientation, nuchal rigidity, headache, drowsiness, and seizures. Although many INKV and CHATV infections appear to be subclinical, these viruses can cause more severe disease, especially in children. PMID:27088268

  6. Bovine viral diarrhea virus (BVDV) infections in pigs.

    PubMed

    Tao, Jie; Liao, Jinhu; Wang, Yin; Zhang, Xinjun; Wang, Jianye; Zhu, Guoqiang

    2013-08-30

    Cattle are the natural hosts of bovine viral diarrhea virus (BVDV), which causes mucosal disease, respiratory and gastrointestinal tract infections, and reproductive problems in cattle. However, BVDV can also infect goats, sheep, deer, and pigs. The prevalence of BVDV infection in pig herds has substantially increased in the last several years, causing increased economic losses to the global pig breeding industry. This article is a summary of BVDV infections in pigs, including a historical overview, clinical signs, pathology, source of infection, genetic characteristics, impacts of porcine BVDV infection for diagnosis of classical swine fever virus (CSFV), differentiation of infection with CSFV and BVDV, and future prospects of porcine BVDV infection.

  7. Immunological alterations in hepatitis C virus infection.

    PubMed

    Calvaruso, Vincenza; Craxì, Antonio

    2013-12-21

    A higher prevalence of immunological processes has recently been reported in patients with hepatitis C virus (HCV) infection, focusing the attention of physicians and researchers on the close association between HCV and immune disorders. HCV lymphotropism represents the most important step in the pathogenesis of virus-related immunological diseases and experimental, virologic, and clinical evidence has demonstrated a trigger role for HCV both in systemic autoimmune diseases, such as rheumatoid arthritis, Sjögren syndrome, hemolytic anemia and severe thrombocytopenia, and in organ-specific autoimmune diseases, such as autoimmune hepatitis, thyroid disorders and diabetes. This review will outline the principal aspects of such HCV-induced immunological alterations, focusing on the prevalence of these less characterized HCV extrahepatic manifestations.

  8. Neurological manifestations of Zika virus infection

    PubMed Central

    Blázquez, Ana-Belén; Saiz, Juan-Carlos

    2016-01-01

    Zika virus (ZIKV) is a flavivirus (Flaviviridae family) transmitted mainly by Aedes mosquitoes. The virus was restricted to the African continent until its spread to south-east Asia in the 1980’s, the Micronesia in 2007, the French Polynesia in 2013 and, more recently in the Americas in 2015, where, up to date, the World Health Organization (WHO) has estimated about 3-4 million total cases of ZIKV infection. During outbreaks in the French Polynesia and Brazil in 2013 and 2015, respectively, national health authorities reported potential neurological complications of ZIKV disease, chiefly an upsurge in Guillain-Barré syndrome, which coincided with ZIKV outbreaks. On the other hand, the emergence of ZIKV in Brazil has been associated with a striking increase in the number of reported cases of microcephaly in fetus and newborns, twenty times higher than in that reported in previous years. While investigations are currently assessing whether there is an actual association between neurological complications and ZIKV infections, the evidence was enough worrisome for WHO to declare a public health emergency of international concern. Here we present an updated review addressing what is currently known about the possible association between ZIKV infection and the development of severe neurological disorders. PMID:27878100

  9. Phosphatidylinositol inhibits respiratory syncytial virus infection

    PubMed Central

    Numata, Mari; Kandasamy, Pitchaimani; Nagashima, Yoji; Fickes, Rachel; Murphy, Robert C.; Voelker, Dennis R.

    2015-01-01

    Respiratory syncytial virus (RSV) infects nearly all children under age 2, and reinfection occurs throughout life, seriously impacting adults with chronic pulmonary diseases. Recent data demonstrate that the anionic pulmonary surfactant lipid phosphatidylglycerol (PG) exerts a potent antiviral effect against RSV in vitro and in vivo. Phosphatidylinositol (PI) is also an anionic pulmonary surfactant phospholipid, and we tested its antiviral activity. PI liposomes completely suppress interleukin-8 production from BEAS2B epithelial cells challenged with RSV. The presence of PI during viral challenge in vitro reduces infection by a factor of >103. PI binds RSV with high affinity, preventing virus attachment to epithelial cells. Intranasal inoculation with PI along with RSV in mice reduces the viral burden 30-fold, eliminates the influx of inflammatory cells, and reduces tissue histopathology. Pharmacological doses of PI persist for >6 h in mouse lung. Pretreatment of mice with PI at 2 h prior to viral infection effectively suppresses inflammation and reduces the viral burden by 85%. These data demonstrate that PI has potent antiviral properties, a long residence time in the extracellular bronchoalveolar compartment, and a significant prophylaxis window. The findings demonstrate PG and PI have complementary roles as intrinsic, innate immune antiviral mediators in the lung. PMID:25561461

  10. Vaccines for herpes simplex virus infections.

    PubMed

    Koelle, David M

    2006-02-01

    Infections with herpes simplex virus (HSV) type 1 (HSV-1) and type 2 (HSV-2) can have serious medical consequences. Although antiviral medications can suppress symptomatic disease, asymptomatic shedding and transmission, they neither cure nor alter the natural history of HSV infections. Manipulation of the immune response is one potential method to decrease disease burden. Current research on prophylactic and therapeutic vaccination approaches is discussed in this review, with a focus on compounds that have entered clinical trials or that display novel compositions or proposed mechanisms of action. One such vaccine is an alum and monophosphoryl lipid A-adjuvanted subunit glycoprotein D2 vaccine that has demonstrated activity in the prevention of HSV-2 infection and disease in HSV-uninfected women in a phase III clinical trial. Further confirmatory clinical trials of this vaccine are currently underway. Other vaccine formats also in development include attenuated live or replication-incompetent HSV-2 strains and technologies that target virus-specific CD8 T-cell responses.

  11. Schmallenberg virus experimental infection of sheep.

    PubMed

    Wernike, Kerstin; Hoffmann, Bernd; Bréard, Emmanuel; Bøtner, Anette; Ponsart, Claire; Zientara, Stéphan; Lohse, Louise; Pozzi, Nathalie; Viarouge, Cyril; Sarradin, Pierre; Leroux-Barc, Céline; Riou, Mickael; Laloy, Eve; Breithaupt, Angele; Beer, Martin

    2013-10-25

    Since late 2011, a novel orthobunyavirus, named Schmallenberg virus (SBV), has been implicated in many cases of severely malformed bovine and ovine offspring in Europe. In adult cattle, SBV is known to cause a mild transient disease; clinical signs include short febrile episodes, decreased milk production and diarrhoea for a few days. However, the knowledge about clinical signs and pathogenesis in adult sheep is limited. In the present study, adult sheep of European domestic breeds were inoculated with SBV either as cell culture grown virus or as virus with no history of passage in cell cultures. Various experimental set-ups were used. Sampling included blood collection at different time points during the experimental period and selected organ material at autopsy. Data from this study showed, that the RNAemic period in sheep was as short as reported for cattle; viral genome was detectable for about 3-5 days by real-time RT-PCR. In total, 13 out of 30 inoculated sheep became RNAemic, with the highest viral load in animals inoculated with virus from low cell culture passaged or the animal passaged material. Contact animals remained negative throughout the study. One RNAemic sheep showed diarrhoea for several days, but fever was not recorded in any of the animals. Antibodies were first detectable 10-14 days post inoculation. Viral RNA was detectable in spleen and lymph nodes up to day 44 post inoculation. In conclusion, as described for cattle, SBV-infection in adult sheep predominantly results in subclinical infection, transient RNAemia and a specific antibody response. Maintenance of viral RNA in the lymphoreticular system is observed for an extended period.

  12. Effects in calves of mixed infections with bovine viral diarrhea virus and several other bovine viruses.

    PubMed

    Castrucci, G; Ferrari, M; Traldi, V; Tartaglione, E

    1992-10-01

    The objective of this study was to verify whether a mixed infection in calves with bovine viral diarrhea virus (BVDV) and other bovine viruses, such as bovid herpesvirus-4 (BHV-4), parainfluenza-3 (PI-3) and infectious bovine rhinotracheitis (IBR) virus, would influence the pathogenesis of the BVDV infection sufficiently to result in the typical form of mucosal disease being produced. Accordingly, two experiments were undertaken. In one experiment calves were first infected with BVDV and subsequently with BHV-4 and IBR virus, respectively. The second experiment consisted in a simultaneous infection of calves with BVDV and PI-3 virus or BVDV and IBR virus. From the first experiment it seems that BVDV infection can be reactivated in calves by BHV-4 and IBR virus. Evidence of this is that BVDV, at least the cytopathic (CP) strain, was recovered from calves following superinfection. Moreover, following such superinfection the calves showed signs which could most likely be ascribed to the pathogenetic activity of BVDV. Superinfection, especially by IBR virus, created a more severe clinical response in calves that were initially infected with CP BVDV, than in those previously given the non-cytopathic (NCP) biotype of the virus. Simultaneous infection with PI-3 virus did not seem to modify to any significant extent the pathogenesis of the experimentally induced BVDV infection whereas a severe clinical response was observed in calves when simultaneous infection was made with BVDV and IBR virus.

  13. Human immunodeficiency virus infection in childhood.

    PubMed

    Blokzijl, M L

    1988-03-01

    Acquired immunodeficiency syndrome is associated with considerable morbidity in infants and children. It is caused by human immunodeficiency virus (HIV) which can be transmitted vertically from mother to infant early in pregnancy. Transmission might also occur via breast milk. Although the exact transmission rate of HIV from mother to infant is not known, HIV can become a major threat to child survival. This threat is already present in Africa where high seroprevalences have been reported among infants and young children. Transmission via blood products is decreasing due to reliable methods of screening donors for HIV antibody. Where these tests are not available, parenteral transmission will increase the incidence of HIV infection. The clinical picture of HIV infection in children presents with failure to thrive, pulmonary interstitial pneumonitis, hepatosplenomegaly and recurrent bacterial infections. These are common manifestations of diseases prevalent in children in Africa where malnutrition and recurrent parasitic infections already cause immunosuppression. Recognition of the syndrome is therefore difficult. There is no available cure for HIV infection. Supportive treatment and relief of pain and suffering are the only means of management at present. Prevention of spread of the illness to infants and young children is therefore of paramount importance.

  14. Update on occult hepatitis B virus infection

    PubMed Central

    Makvandi, Manoochehr

    2016-01-01

    The event of mutations in the surface antigen gene of hepatitis B virus (HBV) results in undetectable hepatitis B surface antigen with positive/negative anti-hepatitis B core (anti-HBc) antibody status in serum and this phenomenon is named occult hepatitis B infection (OBI). The presence of anti-HBc antibody in serum is an important key for OBI tracking, although about 20% of OBI cases are negative for anti-HBc antibody. The diagnosis of OBI is mainly based on polymerase chain reaction (PCR) and real-time PCR assays. However, real-time PCR is a more reliable method than PCR. OBI is a great issue for the public health problem and a challenge for the clinical entity worldwide. The persistence of OBI may lead to the development of cirrhosis and hepatocellular carcinoma. With regard to OBI complications, the screening of HBV DNA by the highly sensitive molecular means should be implemented for: (1) patients with a previous history of chronic or acute HBV infection; (2) patients co-infected with hepatitis C virus/human immunodeficiency virus; (3) patients undergoing chemotherapy or anti-CD20 therapy; (4) recipients of organ transplant; (5) blood donors; (6) organ transplant donors; (7) thalassemia and hemophilia patients; (8) health care workers; (9) patients with liver related disease (cryptogenic); (10) hemodialysis patients; (11) patients undergoing lamivudine or interferon therapy; and (12) children in time of HBV vaccination especially in highly endemic areas of HBV. Active HBV vaccination should be implemented for the close relatives of patients who are negative for OBI markers. Thus, the goal of this review is to evaluate the rate of OBI with a focus on status of high risk groups in different regions of the world. PMID:27818588

  15. Animal models of respiratory syncytial virus infection.

    PubMed

    Taylor, Geraldine

    2017-01-11

    Human respiratory syncytial virus (hRSV) is a major cause of respiratory disease and hospitalisation of infants, worldwide, and is also responsible for significant morbidity in adults and excess deaths in the elderly. There is no licensed hRSV vaccine or effective therapeutic agent. However, there are a growing number of hRSV vaccine candidates that have been developed targeting different populations at risk of hRSV infection. Animal models of hRSV play an important role in the preclinical testing of hRSV vaccine candidates and although many have shown efficacy in preclinical studies, few have progressed to clinical trials or they have had only limited success. This is, at least in part, due to the lack of animal models that fully recapitulate the pathogenesis of hRSV infection in humans. This review summarises the strengths and limitations of animal models of hRSV, which include those in which hRSV is used to infect non-human mammalian hosts, and those in which non-human pneumoviruses, such as bovine (b)RSV and pneumonia virus of mice (PVM) are studied in their natural host. Apart from chimpanzees, other non-human primates (NHP) are only semi-permissive for hRSV replication and experimental infection with large doses of virus result in little or no clinical signs of disease, and generally only mild pulmonary pathology. Other animal models such as cotton rats, mice, ferrets, guinea pigs, hamsters, chinchillas, and neonatal lambs are also only semi-permissive for hRSV. Nevertheless, mice and cotton rats have been of value in the development of monoclonal antibody prophylaxis for infants at high risk of severe hRSV infection and have provided insights into mechanisms of immunity to and pathogenesis of hRSV. However, the extent to which they predict hRSV vaccine efficacy and safety is unclear and several hRSV vaccine candidates that are completely protective in rodent models are poorly effective in chimpanzees and other NHP, such as African Green monkeys. Furthermore

  16. Comparison of three commercial vaccines for preventing persistent infection with bovine viral diarrhea virus.

    PubMed

    Rodning, Soren P; Marley, M Shonda D; Zhang, Yijing; Eason, Andrew B; Nunley, Callie L; Walz, Paul H; Riddell, Kay P; Galik, Patricia K; Brodersen, Bruce W; Givens, M Daniel

    2010-05-01

    Eighty crossbred beef heifers were randomly allocated to four groups to evaluate the efficacy of vaccination in preventing development of calves persistently infected with bovine viral diarrhea virus (BVDV). Group 1 (n=11) was non-vaccinated controls, whereas three groups were vaccinated with commercially available multivalent BVDV vaccines at weaning (approximately 7 mo of age), 28 d post-weaning, approximately 1 y of age, and 28 d later. Groups 2 (n=23) and 3 (n=23) were given a modified-live BVDV vaccine, whereas Group 4 was given an inactivated BVDV vaccine. Heifers were bred by AI and subsequently exposed to two bulls. At 61 d after AI, 70 heifers were pregnant (n=10 for Group 1 and n=20/group for Groups 2, 3, and 4). Three cattle persistently infected with BVDV were commingled with the pregnant heifers (in an isolated pasture) from 68 to 126 d after AI. Thereafter, viremias were detected in pregnant heifers from Groups 1, 3, and 4 (10/10, 1/20, and 10/20, respectively), but not in pregnant heifers from Group 2 (0/20). Resulting calves were assessed for persistent infection using serum PCR, ear notch antigen capture-ELISA, and immunohistochemistry. Persistently infected calves were only produced in Group 1 (10/10) and Group 4 (2/18). In conclusion, commercial vaccines provided effective fetal protection despite prolonged natural exposure to BVDV. Given that viremias were detected in 11 vaccinated heifers after BVDV exposure, and two vaccinated heifers gave birth to persistently infected calves, there is continued need for biosecurity and diagnostic surveillance, in addition to vaccination, to ensure effective BVDV control.

  17. Emerging drugs for respiratory syncytial virus infection.

    PubMed

    Olszewska, Wieslawa; Openshaw, Peter

    2009-06-01

    Although respiratory syncytial virus (RSV) was discovered > 40 years ago, treatment remains largely supportive. There are no safe and effective vaccines or specific treatments other than prophylaxis with passive antibody therapy (palivizumab). However, there are good reasons to think that the scene may soon change. As the pace of development of anti-viral drugs accelerates and optimism over vaccines increases, novel therapies are set to make a major impact in the management of this very common infection. The use and effect of such interventions are not easy to anticipate, but could ultimately include the interruption of RSV's transmission resulting in profound changes to the impact of RSV on human health.

  18. The ecology of viruses that infect eukaryotic algae.

    PubMed

    Short, Steven M

    2012-09-01

    Because viruses of eukaryotic algae are incredibly diverse, sweeping generalizations about their ecology are rare. These obligate parasites infect a range of algae and their diversity can be illustrated by considering that isolates range from small particles with ssRNA genomes to much larger particles with 560 kb dsDNA genomes. Molecular research has also provided clues about the extent of their diversity especially considering that genetic signatures of algal viruses in the environment rarely match cultivated viruses. One general concept in algal virus ecology that has emerged is that algal viruses are very host specific and most infect only certain strains of their hosts; with the exception of viruses of brown algae, evidence for interspecies infectivity is lacking. Although some host-virus systems behave with boom-bust oscillations, complex patterns of intraspecies infectivity can lead to host-virus coexistence obfuscating the role of viruses in host population dynamics. Within the framework of population dynamics, host density dependence is an important phenomenon that influences virus abundances in nature. Variable burst sizes of different viruses also influence their abundances and permit speculations about different life strategies, but as exceptions are common in algal virus ecology, life strategy generalizations may not be broadly applicable. Gaps in knowledge of virus seasonality and persistence are beginning to close and investigations of environmental reservoirs and virus resilience may answer questions about virus inter-annual recurrences. Studies of algal mortality have shown that viruses are often important agents of mortality reinforcing notions about their ecological relevance, while observations of the surprising ways viruses interact with their hosts highlight the immaturity of our understanding. Considering that just two decades ago algal viruses were hardly acknowledged, recent progress affords the optimistic perspective that future studies

  19. Hepatitis B virus infection in Indonesia.

    PubMed

    Yano, Yoshihiko; Utsumi, Takako; Lusida, Maria Inge; Hayashi, Yoshitake

    2015-10-14

    Approximately 240 million people are chronically infected with hepatitis B virus (HBV), 75% of whom reside in Asia. Approximately 600000 of infected patients die each year due to HBV-related diseases or hepatocellular carcinoma (HCC). The endemicity of hepatitis surface antigen in Indonesia is intermediate to high with a geographical difference. The risk of HBV infection is high in hemodialysis (HD) patients, men having sex with men, and health care workers. Occult HBV infection has been detected in various groups such as blood donors, HD patients, and HIV-infected individuals and children. The most common HBV subgenotype in Indonesia is B3 followed by C1. Various novel subgenotypes of HBV have been identified throughout Indonesia, with the novel HBV subgenotypes C6-C16 and D6 being successfully isolated. Although a number of HBV subgenotypes have been discovered in Indonesia, genotype-related pathogenicity has not yet been elucidated in detail. Therefore, genotype-related differences in the prognosis of liver disease and their effects on treatments need to be determined. A previous study conducted in Indonesia revealed that hepatic steatosis was associated with disease progression. Pre-S2 mutations and mutations at C1638T and T1753V in HBV/B3 have been associated with advanced liver diseases including HCC. However, drug resistance to lamivudine, which is prominent in Indonesia, remains obscure. Although the number of studies on HBV in Indonesia has been increasing, adequate databases on HBV infection are limited. We herein provided an overview of the epidemiology and clinical characteristics of HBV infection in Indonesia.

  20. Hepatitis B virus infection in Indonesia

    PubMed Central

    Yano, Yoshihiko; Utsumi, Takako; Lusida, Maria Inge; Hayashi, Yoshitake

    2015-01-01

    Approximately 240 million people are chronically infected with hepatitis B virus (HBV), 75% of whom reside in Asia. Approximately 600000 of infected patients die each year due to HBV-related diseases or hepatocellular carcinoma (HCC). The endemicity of hepatitis surface antigen in Indonesia is intermediate to high with a geographical difference. The risk of HBV infection is high in hemodialysis (HD) patients, men having sex with men, and health care workers. Occult HBV infection has been detected in various groups such as blood donors, HD patients, and HIV-infected individuals and children. The most common HBV subgenotype in Indonesia is B3 followed by C1. Various novel subgenotypes of HBV have been identified throughout Indonesia, with the novel HBV subgenotypes C6-C16 and D6 being successfully isolated. Although a number of HBV subgenotypes have been discovered in Indonesia, genotype-related pathogenicity has not yet been elucidated in detail. Therefore, genotype-related differences in the prognosis of liver disease and their effects on treatments need to be determined. A previous study conducted in Indonesia revealed that hepatic steatosis was associated with disease progression. Pre-S2 mutations and mutations at C1638T and T1753V in HBV/B3 have been associated with advanced liver diseases including HCC. However, drug resistance to lamivudine, which is prominent in Indonesia, remains obscure. Although the number of studies on HBV in Indonesia has been increasing, adequate databases on HBV infection are limited. We herein provided an overview of the epidemiology and clinical characteristics of HBV infection in Indonesia. PMID:26478663

  1. Hepatitis C virus infection protein network.

    PubMed

    de Chassey, B; Navratil, V; Tafforeau, L; Hiet, M S; Aublin-Gex, A; Agaugué, S; Meiffren, G; Pradezynski, F; Faria, B F; Chantier, T; Le Breton, M; Pellet, J; Davoust, N; Mangeot, P E; Chaboud, A; Penin, F; Jacob, Y; Vidalain, P O; Vidal, M; André, P; Rabourdin-Combe, C; Lotteau, V

    2008-01-01

    A proteome-wide mapping of interactions between hepatitis C virus (HCV) and human proteins was performed to provide a comprehensive view of the cellular infection. A total of 314 protein-protein interactions between HCV and human proteins was identified by yeast two-hybrid and 170 by literature mining. Integration of this data set into a reconstructed human interactome showed that cellular proteins interacting with HCV are enriched in highly central and interconnected proteins. A global analysis on the basis of functional annotation highlighted the enrichment of cellular pathways targeted by HCV. A network of proteins associated with frequent clinical disorders of chronically infected patients was constructed by connecting the insulin, Jak/STAT and TGFbeta pathways with cellular proteins targeted by HCV. CORE protein appeared as a major perturbator of this network. Focal adhesion was identified as a new function affected by HCV, mainly by NS3 and NS5A proteins.

  2. Hepatitis C virus infection protein network

    PubMed Central

    de Chassey, B; Navratil, V; Tafforeau, L; Hiet, M S; Aublin-Gex, A; Agaugué, S; Meiffren, G; Pradezynski, F; Faria, B F; Chantier, T; Le Breton, M; Pellet, J; Davoust, N; Mangeot, P E; Chaboud, A; Penin, F; Jacob, Y; Vidalain, P O; Vidal, M; André, P; Rabourdin-Combe, C; Lotteau, V

    2008-01-01

    A proteome-wide mapping of interactions between hepatitis C virus (HCV) and human proteins was performed to provide a comprehensive view of the cellular infection. A total of 314 protein–protein interactions between HCV and human proteins was identified by yeast two-hybrid and 170 by literature mining. Integration of this data set into a reconstructed human interactome showed that cellular proteins interacting with HCV are enriched in highly central and interconnected proteins. A global analysis on the basis of functional annotation highlighted the enrichment of cellular pathways targeted by HCV. A network of proteins associated with frequent clinical disorders of chronically infected patients was constructed by connecting the insulin, Jak/STAT and TGFβ pathways with cellular proteins targeted by HCV. CORE protein appeared as a major perturbator of this network. Focal adhesion was identified as a new function affected by HCV, mainly by NS3 and NS5A proteins. PMID:18985028

  3. Secondary bacterial infections in influenza virus infection pathogenesis.

    PubMed

    Smith, Amber M; McCullers, Jonathan A

    2014-01-01

    Influenza is often complicated by bacterial pathogens that colonize the nasopharynx and invade the middle ear and/or lung epithelium. Incidence and pathogenicity of influenza-bacterial coinfections are multifactorial processes that involve various pathogenic virulence factors and host responses with distinct site- and strain-specific differences. Animal models and kinetic models have improved our understanding of how influenza viruses interact with their bacterial co-pathogens and the accompanying immune responses. Data from these models indicate that considerable alterations in epithelial surfaces and aberrant immune responses lead to severe inflammation, a key driver of bacterial acquisition and infection severity following influenza. However, further experimental and analytical studies are essential to determining the full mechanistic spectrum of different viral and bacterial strains and species and to finding new ways to prevent and treat influenza-associated bacterial coinfections. Here, we review recent advances regarding transmission and disease potential of influenza-associated bacterial infections and discuss the current gaps in knowledge.

  4. Spatiotemporal Dynamics of Virus Infection Spreading in Tissues.

    PubMed

    Bocharov, Gennady; Meyerhans, Andreas; Bessonov, Nickolai; Trofimchuk, Sergei; Volpert, Vitaly

    2016-01-01

    Virus spreading in tissues is determined by virus transport, virus multiplication in host cells and the virus-induced immune response. Cytotoxic T cells remove infected cells with a rate determined by the infection level. The intensity of the immune response has a bell-shaped dependence on the concentration of virus, i.e., it increases at low and decays at high infection levels. A combination of these effects and a time delay in the immune response determine the development of virus infection in tissues like spleen or lymph nodes. The mathematical model described in this work consists of reaction-diffusion equations with a delay. It shows that the different regimes of infection spreading like the establishment of a low level infection, a high level infection or a transition between both are determined by the initial virus load and by the intensity of the immune response. The dynamics of the model solutions include simple and composed waves, and periodic and aperiodic oscillations. The results of analytical and numerical studies of the model provide a systematic basis for a quantitative understanding and interpretation of the determinants of the infection process in target organs and tissues from the image-derived data as well as of the spatiotemporal mechanisms of viral disease pathogenesis, and have direct implications for a biopsy-based medical testing of the chronic infection processes caused by viruses, e.g. HIV, HCV and HBV.

  5. Spatiotemporal Dynamics of Virus Infection Spreading in Tissues

    PubMed Central

    Meyerhans, Andreas; Bessonov, Nickolai; Trofimchuk, Sergei; Volpert, Vitaly

    2016-01-01

    Virus spreading in tissues is determined by virus transport, virus multiplication in host cells and the virus-induced immune response. Cytotoxic T cells remove infected cells with a rate determined by the infection level. The intensity of the immune response has a bell-shaped dependence on the concentration of virus, i.e., it increases at low and decays at high infection levels. A combination of these effects and a time delay in the immune response determine the development of virus infection in tissues like spleen or lymph nodes. The mathematical model described in this work consists of reaction-diffusion equations with a delay. It shows that the different regimes of infection spreading like the establishment of a low level infection, a high level infection or a transition between both are determined by the initial virus load and by the intensity of the immune response. The dynamics of the model solutions include simple and composed waves, and periodic and aperiodic oscillations. The results of analytical and numerical studies of the model provide a systematic basis for a quantitative understanding and interpretation of the determinants of the infection process in target organs and tissues from the image-derived data as well as of the spatiotemporal mechanisms of viral disease pathogenesis, and have direct implications for a biopsy-based medical testing of the chronic infection processes caused by viruses, e.g. HIV, HCV and HBV. PMID:27997613

  6. Hepatitis C virus infection in the human immunodeficiency virus infected patient.

    PubMed

    Clausen, Louise Nygaard; Lundbo, Lene Fogt; Benfield, Thomas

    2014-09-14

    Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) share the same transmission routes; therefore, coinfection is frequent. An estimated 5-10 million individuals alone in the western world are infected with both viruses. The majority of people acquire HCV by injection drug use and, to a lesser extent, through blood transfusion and blood products. Recently, there has been an increase in HCV infections among men who have sex with men. In the context of effective antiretroviral treatment, liver-related deaths are now more common than Acquired Immune Deficiency Syndrome-related deaths among HIV-HCV coinfected individuals. Morbidity and mortality rates from chronic HCV infection will increase because the infection incidence peaked in the mid-1980s and because liver disease progresses slowly and is clinically silent to cirrhosis and end-stage-liver disease over a 15-20 year time period for 15%-20% of chronically infected individuals. HCV treatment has rapidly changed with the development of new direct-acting antiviral agents; therefore, cure rates have greatly improved because the new treatment regimens target different parts of the HCV life cycle. In this review, we focus on the epidemiology, diagnosis and the natural course of HCV as well as current and future strategies for HCV therapy in the context of HIV-HCV coinfection in the western world.

  7. Honey Bee Infecting Lake Sinai Viruses

    PubMed Central

    Daughenbaugh, Katie F.; Martin, Madison; Brutscher, Laura M.; Cavigli, Ian; Garcia, Emma; Lavin, Matt; Flenniken, Michelle L.

    2015-01-01

    Honey bees are critical pollinators of important agricultural crops. Recently, high annual losses of honey bee colonies have prompted further investigation of honey bee infecting viruses. To better characterize the recently discovered and very prevalent Lake Sinai virus (LSV) group, we sequenced currently circulating LSVs, performed phylogenetic analysis, and obtained images of LSV2. Sequence analysis resulted in extension of the LSV1 and LSV2 genomes, the first detection of LSV4 in the US, and the discovery of LSV6 and LSV7. We detected LSV1 and LSV2 in the Varroa destructor mite, and determined that a large proportion of LSV2 is found in the honey bee gut, suggesting that vector-mediated, food-associated, and/or fecal-oral routes may be important for LSV dissemination. Pathogen-specific quantitative PCR data, obtained from samples collected during a small-scale monitoring project, revealed that LSV2, LSV1, Black queen cell virus (BQCV), and Nosema ceranae were more abundant in weak colonies than strong colonies within this sample cohort. Together, these results enhance our current understanding of LSVs and illustrate the importance of future studies aimed at investigating the role of LSVs and other pathogens on honey bee health at both the individual and colony levels. PMID:26110586

  8. Honey Bee Infecting Lake Sinai Viruses.

    PubMed

    Daughenbaugh, Katie F; Martin, Madison; Brutscher, Laura M; Cavigli, Ian; Garcia, Emma; Lavin, Matt; Flenniken, Michelle L

    2015-06-23

    Honey bees are critical pollinators of important agricultural crops. Recently, high annual losses of honey bee colonies have prompted further investigation of honey bee infecting viruses. To better characterize the recently discovered and very prevalent Lake Sinai virus (LSV) group, we sequenced currently circulating LSVs, performed phylogenetic analysis, and obtained images of LSV2. Sequence analysis resulted in extension of the LSV1 and LSV2 genomes, the first detection of LSV4 in the US, and the discovery of LSV6 and LSV7. We detected LSV1 and LSV2 in the Varroa destructor mite, and determined that a large proportion of LSV2 is found in the honey bee gut, suggesting that vector-mediated, food-associated, and/or fecal-oral routes may be important for LSV dissemination. Pathogen-specific quantitative PCR data, obtained from samples collected during a small-scale monitoring project, revealed that LSV2, LSV1, Black queen cell virus (BQCV), and Nosema ceranae were more abundant in weak colonies than strong colonies within this sample cohort. Together, these results enhance our current understanding of LSVs and illustrate the importance of future studies aimed at investigating the role of LSVs and other pathogens on honey bee health at both the individual and colony levels.

  9. Peptide inhibitors against herpes simplex virus infections.

    PubMed

    Galdiero, Stefania; Falanga, Annarita; Tarallo, Rossella; Russo, Luigi; Galdiero, Emilia; Cantisani, Marco; Morelli, Giancarlo; Galdiero, Massimiliano

    2013-03-01

    Herpes simplex virus (HSV) is a significant human pathogen causing mucocutaneous lesions primarily in the oral or genital mucosa. Although acyclovir (ACV) and related nucleoside analogs provide successful treatment, HSV remains highly prevalent worldwide and is a major cofactor for the spread of human immunodeficiency virus. Encephalitis, meningitis, and blinding keratitis are among the most severe diseases caused by HSV. ACV resistance poses an important problem for immunocompromised patients and highlights the need for new safe and effective agents; therefore, the development of novel strategies to eradicate HSV is a global public health priority. Despite the continued global epidemic of HSV and extensive research, there have been few major breakthroughs in the treatment or prevention of the virus since the introduction of ACV in the 1980s. A therapeutic strategy at the moment not fully addressed is the use of small peptide molecules. These can be either modeled on viral proteins or derived from antimicrobial peptides. Any peptide that interrupts protein-protein or viral protein-host cell membrane interactions is potentially a novel antiviral drug and may be a useful tool for elucidating the mechanisms of viral entry. This review summarizes current knowledge and strategies in the development of synthetic and natural peptides to inhibit HSV infectivity.

  10. 78 FR 33848 - Draft Guidance for Industry on Human Immunodeficiency Virus-1 Infection: Developing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-05

    ... No. FDA-2013-D-0589] Draft Guidance for Industry on Human Immunodeficiency Virus-1 Infection... guidance for industry entitled ``Human Immunodeficiency Virus-1 Infection: Developing Antiretroviral Drugs... guidance for industry entitled ``Human Immunodeficiency Virus-1 Infection: Developing Antiretroviral...

  11. Oral manifestations of hepatitis C virus infection

    PubMed Central

    Carrozzo, Marco; Scally, Kara

    2014-01-01

    Extrahepatic manifestations (EHMs) of hepatitis C virus (HCV) infection can affect a variety of organ systems with significant morbidity and mortality. Some of the most frequently reported EHM of HCV infection, involve the oral region predominantly or exclusively. Oral lichen planus (OLP) is a chronic inflammatory condition that is potentially malignant and represents cell-mediated reaction to a variety of extrinsic antigens, altered self-antigens, or super antigens. Robust epidemiological evidence support the link between OLP and HCV. As the virus may replicate in the oral mucosa and attract HCV-specific T lymphocytes, HCV may be implicated in OLP pathogenesis. Sjögren syndrome (SjS) is an autoimmune exocrinopathy, characterized by dryness of the mouth and eyes and a multitude of other systemic signs and symptoms. SjS patients have also an increased risk of non-Hodgkin lymphoma. Patients with chronic hepatitis C do frequently have histological signs of Sjögren-like sialadenitis with mild or even absent clinical symptoms. However, it is still unclear if HCV may cause a disease mimicking SjS or it is directly responsible for the development of SjS in a specific subset of patients. Oral squamous cell carcinoma is the most common oral malignant tumour and at least in some part of the world could be linked to HCV. PMID:24976694

  12. Hepatitis C virus infection after renal transplantation.

    PubMed

    Romero, E; Galindo, P; Bravo, J A; Osorio, J M; Pérez, A; Baca, Y; Ferreira, C; Asensio, C; Osuna, A

    2008-11-01

    Hepatitis C virus (HCV) infection is the main cause of liver disease after renal transplantation. Most patients have seroconverted on dialysis to positive RNA. The viral load increases during immunosuppressive therapy. The risk of developing chronic liver disease is related to the histopathologic findings, duration and severity of the disease, immunosuppression, and transplantation time. Hepatitis C virus infection can predict onset, of proteinuria and diabetes. We studied 868 patients who received renal transplants between (1987 and 2006), of whom 18.7% were seropositive for HCV. We observed a higher rate of HCV-seropositive patients related to the duration of hemodialysis therapy. Of the HCV seropositive patients, 77% had received renal allografts before 1998. There was no difference between the sexes; however, the HCV positive patients were younger. Polymerase chain reaction tests results were positive in 91.6% of the patients with HCV antibodies. The prevalence of diabetes was greater among HCV positive patients, as was as the persistence of proteinuria. Cryoglobulins were positive in 30.8%. The incidence of acute rejection episodes in the first year was similar between groups. Of the HCV-positive patients, 80.2% were treated with cyclosporine, most patients continued this therapy throughout the study. We observed no significant difference in mortality end graft survival rate between the two groups. However, renal function differed significantly at some points during the evolution of the clinical course. Renal transplantation is still the best treatment option in patients with chronic renal disease.

  13. Simultaneous multiplex PCR detection of seven cucurbit-infecting viruses.

    PubMed

    Kwon, Ji Yeon; Hong, Jin Sung; Kim, Min Jea; Choi, Sun Hee; Min, Byeong Eun; Song, Eun Gyeong; Kim, Hyun Hee; Ryu, Ki Hyun

    2014-09-01

    Two multiplex polymerase chain reaction (PCR) systems using dual priming oligonucleotide (DPO) primers were developed for the simultaneous detection of seven cucurbit-infecting viruses. One system allows for the detection of papaya ringspot virus, watermelon mosaic virus, and zucchini yellow mosaic virus, whereas the other permits the detection of cucumber green mottle mosaic virus, cucumber fruit mottle mosaic virus, kyuri green mottle mosaic virus, and zucchini green mottle mosaic virus. Viral species-specific DPO primers developed in this study detected as little as 10 fg/μl of viral RNA under monoplex conditions and 10 pg/μl of viral RNA under multiplex conditions. Multiplex PCR using the DPO primer sets was capable of amplifying viral genes at annealing temperatures ranging from 53 °C to 63 °C. Whereas the use of conventional primers gave rise to non-specific bands, the DPO primers detected target viral genes in the absence of non-specific amplification. When these DPO multiplex primer sets were applied to virus-infected cucurbit samples obtained in the field, multiple infection as well as single infection was accurately identified. This novel approach could also detect multiple viruses in infected seeds. The reliability of multiplex PCR systems using DPO primers for plant virus detection is discussed.

  14. Immune responses of patients to orf virus infection.

    PubMed

    Yirrell, D L; Vestey, J P; Norval, M

    1994-04-01

    Orf is a disease of sheep and goats which is caused by a parapox virus. It can be transmitted to humans, and is considered an occupational hazard by those handling sheep. In this paper we present the first report of both cell-mediated and humoral immune responses to naturally acquired orf virus infection in humans. Lymphoproliferative responses of peripheral blood mononuclear cells of patients to an orf virus antigen were vigorous soon after infection, but rapidly declined. Orf virus antibody levels, detected by ELISA, were shown to rise during infection. Western blot analysis confirmed this, and demonstrated that the antibody produced in response to the infection was directed against the 40-kDa viral surface tubule protein. Where direct comparisons were possible, the immune response of humans to orf virus infection was similar to that previously reported for sheep. Evidence was obtained suggesting that prior exposure to vaccinia virus (smallpox vaccination) provided no protection from subsequent orf virus infection. In addition, orf virus infection did not enhance immune responses to vaccinia virus antigens.

  15. Neutralization Assay for Chikungunya Virus Infection: Plaque Reduction Neutralization Test.

    PubMed

    Azami, Nor Azila Muhammad; Moi, Meng Ling; Takasaki, Tomohiko

    2016-01-01

    Neutralization assay is a technique that detects and quantifies neutralizing antibody in serum samples by calculating the percentage of reduction of virus activity, as the concentration of virus used is usually constant. Neutralizing antibody titer is conventionally determined by calculating the percentage reduction in total virus infectivity by counting and comparing number of plaques (localized area of infection due to cytopathic effect) with a standard amount of virus. Conventional neutralizing test uses plaque-reduction neutralization test (PRNT) to determine neutralizing antibody titers against Chikungunya virus (CHIKV). Here we describe the plaque reduction neutralization assay (PRNT) using Vero cell lines to obtain neutralizing antibody titers.

  16. First Imported Case of Zika Virus Infection into Korea.

    PubMed

    Jang, Hee-Chang; Park, Wan Beom; Kim, Uh Jin; Chun, June Young; Choi, Su-Jin; Choe, Pyoeng Gyun; Jung, Sook-In; Jee, Youngmee; Kim, Nam-Joong; Choi, Eun Hwa; Oh, Myoung-Don

    2016-07-01

    Since Zika virus has been spreading rapidly in the Americas from 2015, the outbreak of Zika virus infection becomes a global health emergency because it can cause neurological complications and adverse fetal outcome including microcephaly. Here, we report clinical manifestations and virus isolation findings from a case of Zika virus infection imported from Brazil. The patient, 43-year-old Korean man, developed fever, myalgia, eyeball pain, and maculopapular rash, but not neurological manifestations. Zika virus was isolated from his semen, and reverse-transcriptase PCR was positive for the virus in the blood, urine, and saliva on the 7th day of the illness but was negative on the 21st day. He recovered spontaneously without any neurological complications. He is the first case of Zika virus infection in Korea imported from Brazil.

  17. Mayaro virus infection, Amazon Basin region, Peru, 2010-2013.

    PubMed

    Halsey, Eric S; Siles, Crystyan; Guevara, Carolina; Vilcarromero, Stalin; Jhonston, Erik J; Ramal, Cesar; Aguilar, Patricia V; Ampuero, Julia S

    2013-11-01

    During 2010-2013, we recruited 16 persons with confirmed Mayaro virus infection in the Peruvian Amazon to prospectively follow clinical symptoms and serologic response over a 12-month period. Mayaro virus infection caused long-term arthralgia in more than half, similar to reports of other arthritogenic alphaviruses.

  18. Zika virus infection acquired during brief travel to Indonesia.

    PubMed

    Kwong, Jason C; Druce, Julian D; Leder, Karin

    2013-09-01

    Zika virus infection closely resembles dengue fever. It is possible that many cases are misdiagnosed or missed. We report a case of Zika virus infection in an Australian traveler who returned from Indonesia with fever and rash. Further case identification is required to determine the evolving epidemiology of this disease.

  19. Co-infections with Chikungunya and Dengue Viruses, Guatemala, 2015

    PubMed Central

    Signor, Leticia del Carmen Castillo; Williams, Christopher; Donis, Evelin; Cuevas, Luis E.; Adams, Emily R.

    2016-01-01

    We screened serum samples referred to the national reference laboratory in Guatemala that were positive for chikungunya or dengue viruses in June 2015. Co-infection with both viruses was detected by reverse transcription PCR in 46 (32%) of 144 samples. Specimens should be tested for both arboviruses to detect co-infections. PMID:27767914

  20. Respiratory syncytial virus: co-infection and paediatric lower respiratory tract infections.

    PubMed

    Yoshida, Lay-Myint; Suzuki, Motoi; Nguyen, Hien Anh; Le, Minh Nhat; Dinh Vu, Thiem; Yoshino, Hiroshi; Schmidt, Wolf-Peter; Nguyen, Thi Thuy Ai; Le, Huu Tho; Morimoto, Konosuke; Moriuchi, Hiroyuki; Dang, Duc Anh; Ariyoshi, Koya

    2013-08-01

    Comprehensive population-based data on the role of respiratory viruses in the development of lower respiratory tract infections (LRTIs) remain unclear. We investigated the incidence and effect of single and multiple infections with respiratory viruses on the risk of LRTIs in Vietnam. Population-based prospective surveillance and a case-control study of hospitalised paediatric patients with acute respiratory infection (ARI) were conducted from April 2007 through to March 2010. Healthy controls were randomly recruited from the same community. Nasopharyngeal samples were collected and tested for 13 respiratory viruses using multiplex PCRs. 1992 hospitalised ARI episodes, including 397 (19.9%) with LRTIs, were enrolled. Incidence of hospitalised LRTIs among children aged <24 months was 2171.9 per 100 000 (95% CI 1947.9-2419.7). The majority of ARI cases (60.9%) were positive for at least one virus. Human rhinovirus (24.2%), respiratory syncytial virus (20.1%) and influenza A virus (12.0%) were the most common and 9.5% had multiple-viral infections. Respiratory syncytial virus and human metapneumovirus infections independently increased the risk of LRTIs. Respiratory syncytial virus further increased the risk, when co-infected with human rhinovirus, human metapneumovirus and parainfluenza virus-3 but not with influenza A virus. The case-control analysis revealed that respiratory syncytial virus and influenza A virus increased the risk of ARI hospitalisation but not human rhinovirus. Respiratory syncytial virus is the leading pathogen associated with risk of ARI hospitalisation and LRTIs in Vietnam.

  1. Viremia and Clinical Presentation in Nicaraguan Patients Infected With Zika Virus, Chikungunya Virus, and Dengue Virus

    PubMed Central

    Waggoner, Jesse J.; Gresh, Lionel; Vargas, Maria Jose; Ballesteros, Gabriela; Tellez, Yolanda; Soda, K. James; Sahoo, Malaya K.; Nuñez, Andrea; Balmaseda, Angel; Harris, Eva; Pinsky, Benjamin A.

    2016-01-01

    Background. Zika virus (ZIKV), chikungunya virus (CHIKV), and dengue virus (DENV) cocirculate in Nicaragua. In this study, we sought to compare the quantified viremia and clinical presentation of patients infected with 1 or more of these viruses. Methods. Acute-phase serum samples from 346 patients with a suspected arboviral illness were tested using a multiplex real-time reverse-transcription polymerase chain reaction for ZIKV, CHIKV, and DENV. Viremia was quantitated for each detected virus, and clinical information from request forms submitted with each sample was recorded. Results. A total of 263 patients tested positive for 1 or more viruses: 192 patients tested positive for a single virus (monoinfections) and 71 patients tested positive for 2 or all 3 viruses (coinfections). Quantifiable viremia was lower in ZIKV infections compared with CHIKV or DENV (mean 4.70 vs 6.42 and 5.84 log10 copies/mL serum, respectively; P < .001 for both comparisons), and for each virus, mean viremia was significantly lower in coinfections than in monoinfections. Compared with patients with CHIKV or DENV, ZIKV patients were more likely to have a rash (P < .001) and less likely to be febrile (P < .05) or require hospitalization (P < .001). Among all patients, hospitalized cases had higher viremia than those who did not require hospitalization (7.1 vs 4.1 log10 copies/mL serum, respectively; P < .001). Conclusions. ZIKV, CHIKV, and DENV result in similar clinical presentations, and coinfections may be relatively common. Our findings illustrate the need for accurate, multiplex diagnostics for patient care and epidemiologic surveillance. PMID:27578819

  2. Natural killer cells in hepatitis B virus infection.

    PubMed

    Wu, Shao-fei; Wang, Wen-jing; Gao, Yue-qiu

    2015-01-01

    Natural killer cells are a unique type of lymphocytes with cytotoxic capacity, and play important roles against tumors and infections. Recently, natural killer cells have been increasingly valued in their effects in hepatitis B virus infection. Since hepatitis B virus is not cytopathic, the subsequent antiviral immune responses of the host are responsible for sustaining the liver injury, which may result in cirrhosis and even hepatocellular carcinoma. Many studies have confirmed that natural killer cells participate in anti-hepatitis B virus responses both in the early phase after infection and in the chronic phase via cytolysis, degranulation, and cytokine secretion. However, natural killer cells play dichotomic roles: they exert antiviral and immunoregulatory functions whilst contribute to the pathogenesis of liver injury. Here, we review the roles of natural killer cells in hepatitis B virus infection, introducing novel therapeutic strategies for controlling hepatitis B virus infection via the modulation of natural killer cells.

  3. Bovine respiratory disease model based on dual infections with infection with bovine viral diarrhea virus and bovine corona virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine respiratory disease complex (BRDC) is the leading cause of economic loss in the U.S. cattle industry. BRDC likely results from simultaneous or sequential infections with multiple pathogens including both viruses and bacteria. Bovine viral diarrhea virus (BVDV) and bovine corona virus (BoCV...

  4. Prevalence of occult hepatitis C virus infection in the Iranian patients with human immunodeficiency virus infection.

    PubMed

    Bokharaei-Salim, Farah; Keyvani, Hossein; Esghaei, Maryam; Zare-Karizi, Shohreh; Dermenaki-Farahani, Sahar-Sadat; Hesami-Zadeh, Khashayar; Fakhim, Shahin

    2016-11-01

    Occult hepatitis C virus (HCV) infection is a new form of chronic HCV infection described by the presence of the genomic HCV-RNA in liver biopsy and/or peripheral blood mononuclear cell (PBMC) samples, and undetectable levels or absence of HCV-RNA and in the absence or presence of anti HCV antibodies in the plasma specimens. The aim of the present study was to evaluate the occurrence of occult HCV infection (OCI) among Iranian subjects infected with human immunodeficiency virus (HIV) using RT-nested PCR. From March 2014 until April 2015, 109 Iranian patients with established HIV infection were enrolled in this cross-sectional study. After extraction of viral RNA from the plasma and PBMC samples, HCV-RNA status was examined by RT-nested PCR using primers from the 5'-NTR. HCV genotyping was conducted using RFLP analysis. For the confirmation of HCV genotyping by RFLP method, the PCR products were sequenced. Of the 109 patients, 50 were positive for antibodies against HCV. The HCV-RNA was detected in PBMC specimens in 6 (10.2%) out of the total 59 patients negative for anti-HCV Abs and undetectable plasma HCV-RNA and also from 4 (8.0%) out of the total 50 patients positive for anti-HCV Abs and undetectable plasma HCV-RNA. HCV genotyping analysis showed that 6 (60.0%) patients were infected with HCV subtype 3a, 3 (30.0%) were infected with HCV subtype 1a and 1 (10.0%) patient was infected with HCV subtype 1b. This study revealed the incidence of OCI (9.2%) in HIV-infected Iranian patients. Hence, designing prospective studies focusing on the detection of OCI in these patients would provide more information. J. Med. Virol. 88:1960-1966, 2016. © 2016 Wiley Periodicals, Inc.

  5. Nosocomial viral infections: III. Guidelines for prevention and control of exanthematous viruses, gastroenteritis viruses, picornaviruses, and uncommonly seen viruses.

    PubMed

    Valenti, W M; Hruska, J F; Menegus, M A; Freeburn, M J

    1981-01-01

    This communication is the third in a four-part series on nosocomial viral infections from the Strong Memorial Hospital. This third article discusses guidelines for prevention and control of exanthematous viruses, gastroenteritis, viruses, adenoviruses and the picornaviruses other than rhinoviruses. Several uncommonly seen viruses, such as the virus of Creutzfeldt-Jakob disease and Marburg, Ebola, and Lassa fever viruses, also are reviewed briefly.

  6. Diagnosis of Zika virus infection on a nanotechnology platform.

    PubMed

    Zhang, Bo; Pinsky, Benjamin A; Ananta, Jeyarama S; Zhao, Su; Arulkumar, Shylaja; Wan, Hao; Sahoo, Malaya K; Abeynayake, Janaki; Waggoner, Jesse J; Hopes, Clay; Tang, Meijie; Dai, Hongjie

    2017-03-06

    We developed a multiplexed assay on a plasmonic-gold platform for measuring IgG and IgA antibodies and IgG avidity against both Zika virus (ZIKV) and dengue virus (DENV) infections. In contrast to IgM cross-reactivity, IgG and IgA antibodies against ZIKV nonstructural protein 1 (NS1) antigen were specific to ZIKV infection, and IgG avidity revealed recent ZIKV infection and past DENV-2 infection in patients in dengue-endemic regions. This assay could enable specific diagnosis of ZIKV infection over other flaviviral infections.

  7. Pathology of Lassa Virus Infection in the Rhesus Monkey

    DTIC Science & Technology

    1982-01-01

    examined. Lassa fever ’- is an infectious, febrile disease nuclear cell infiltrates and mucosal hemorrhages. of man caused by Lassa virus (LASV), a member... virus titers, suggests that virus replication 1. Buckley, S. M., and Casals, J., 1973. Lassa fever , in the kidney parenchyma was unlikely. A few a new...A., 1973. Comparative pathology of phology and morphogenesis of arenaviruses . BDg. Lassa virus infection in monkeys, guinea pip, W.H.O., 52: 409-419

  8. Electron microscope evidence of virus infection in cultured marine fish

    NASA Astrophysics Data System (ADS)

    Sun, Xiu-Qin; Zhang, Jin-Xing; Qu, Ling-Yun

    2000-09-01

    Electron microscope investigation on the red sea bream ( Pagrosomus major), bastard halibut ( Paralichthys olivaceus) and stone flounder ( Kareius bicoloratus) in North China revealed virus infection in the bodies of the dead and diseased fish. These viruses included the lymphocystis disease virus (LDV), parvovirus, globular virus, and a kind of baculavirus which was not discovered and reported before and is now tentatively named baculavirus of stone flounder ( Kareius bicoloratus).

  9. Human immunodeficiency virus can productively infect cultured human glial cells.

    PubMed

    Cheng-Mayer, C; Rutka, J T; Rosenblum, M L; McHugh, T; Stites, D P; Levy, J A

    1987-05-01

    Six isolates of the human immunodeficiency virus (HIV) showed differences in their ability to productively infect glioma-derived cell lines and early-passage human brain cell cultures. Susceptibility to HIV infection correlated well with the expression of the astrocyte marker glial fibrillary acidic protein. The CD4 molecule was expressed on some, but not all, of the brain-derived cells; however, no correlation was observed between CD4 protein expression and susceptibility to virus infection. The results show that HIV can productively infect human brain cells, particularly those of glial origin, and suggest that these cell types in the brain can harbor the virus.

  10. Bone health and human immunodeficiency virus infection.

    PubMed

    Schafer, Jason J; Manlangit, Kristine; Squires, Kathleen E

    2013-06-01

    Low bone mineral density is common among persons with human immunodeficiency virus (HIV) infection, and studies reporting increased fracture rates in this patient population are emerging. The causes of low bone mineral density, osteoporosis, and fractures in persons with HIV are likely multifactorial, involving traditional risk factors, HIV infection, and exposure to antiretroviral treatment. Specific antiretrovirals such as tenofovir may cause a greater loss of bone mineral density compared with other agents and have recently been linked to an increased risk for fracture. As a result, recent treatment guidelines suggest that clinicians consider avoiding tenofovir as initial therapy in postmenopausal women. Evaluating bone mineral density and vitamin D status in persons with HIV may be important steps in identifying those requiring pharmacotherapy; however, the appropriate timing for bone mineral density and vitamin D screening is uncertain, as is the appropriate method of replacing vitamin D in HIV-positive patients who are deficient. Further study is necessary to definitively determine the approach to evaluating bone health and managing low bone mineral density and vitamin D deficiency in patients with HIV infection.

  11. Neuralgic amyotrophy and hepatitis E virus infection

    PubMed Central

    van Eijk, Jeroen J.J.; Madden, Richie G.; van der Eijk, Annemiek A.; Hunter, Jeremy G.; Reimerink, Johan H.J.; Bendall, Richard P.; Pas, Suzan D.; Ellis, Vic; van Alfen, Nens; Beynon, Laura; Southwell, Lucy; McLean, Brendan; Jacobs, Bart C.; van Engelen, Baziel G.M.

    2014-01-01

    Objective: To determine whether there is an association between an acute preceding hepatitis E virus (HEV) infection and neuralgic amyotrophy (NA), and if so, whether patients with HEV-related NA differ from patients without an associated HEV infection. Methods: HEV testing was conducted in a retrospective cohort of 28 Cornish patients with NA (2011–2013) and a prospective cohort of 38 consecutive Dutch patients with NA (2004–2007). Acute-phase serum samples were analyzed for the presence of anti-HEV immunoglobulin (Ig) M and IgG and HEV RNA (quantitative real-time PCR). Results: Five cases (10.6%) of acute hepatitis E infection were identified in a total group of 47 patients with NA of whom serum samples were available. In 4 patients, HEV RNA was detected in serum samples taken at presentation. All patients with HEV-associated NA had clinical and electrophysiologic evidence of bilateral brachial plexus involvement. Anti-HEV IgM positivity was not related to age, sex, disease severity, disease course, or outcome. Conclusions: Acute hepatitis E is found in 10% of patients with NA from the United Kingdom and the Netherlands. Further research is required to investigate the role of HEV in NA in other geographical locations and to determine pathophysiologic mechanisms. PMID:24401685

  12. Infection with a plant virus modifies vector feeding behavior

    PubMed Central

    Stafford, Candice A.; Walker, Gregory P.; Ullman, Diane E.

    2011-01-01

    Vector infection by some animal-infecting parasites results in altered feeding that enhances transmission. Modification of vector behavior is of broad adaptive significance, as parasite fitness relies on passage to a new host, and vector feeding is nearly always essential for transmission. Although several plant viruses infect their insect vectors, we have shown that vector infection by a plant virus alters feeding behavior. Here we show that infection with Tomato spotted wilt virus (TSWV), type member of the only plant-infecting genus in the Bunyaviridae, alters the feeding behavior of its thrips vector, Frankliniella occidentalis (Pergande). Male thrips infected with TSWV fed more than uninfected males, with the frequency of all feeding behaviors increasing by up to threefold, thus increasing the probability of virus inoculation. Importantly, infected males made almost three times more noningestion probes (probes in which they salivate, but leave cells largely undamaged) compared with uninfected males. A functional cell is requisite for TSWV infection and cell-to-cell movement; thus, this behavior is most likely to establish virus infection. Some animal-infecting members of the Bunyaviridae (La Crosse virus and Rift Valley fever virus) also cause increased biting rates in infected vectors. Concomitantly, these data support the hypothesis that capacity to modify vector feeding behavior is a conserved trait among plant- and animal-infecting members of the Bunyaviridae that evolved as a mechanism to enhance virus transmission. Our results underscore the evolutionary importance of vector behavioral modification to diverse parasites with host ranges spanning both plant and animal kingdoms. PMID:21606372

  13. Limiting influenza virus, HIV and dengue virus infection by targeting viral proteostasis

    PubMed Central

    Heaton, Nicholas S.; Moshkina, Natasha; Fenouil, Romain; Gardner, Thomas J.; Aguirre, Sebastian; Shah, Priya S.; Zhao, Nan; Manganaro, Lara; Hultquist, Judd; Noel, Justine; Sachs, David; Hamilton, Jennifer; Leon, Paul E.; Chawdury, Amit; Tripathy, Shashank; Melegari, Camilla; Campisi, Laura; Hai, Rong; Metreveli, Giorgi; Gamarnik, Andrea V.; García-Sastre, Adolfo; Greenbaum, Benjamin; Simon, Viviana; Fernandez-Sesma, Ana; Krogan, Nevan; Mulder, Lubbertus C.F.; van Bakel, Harm; Tortorella, Domenico; Taunton, Jack; Palese, Peter; Marazzi, Ivan

    2016-01-01

    Viruses are obligate parasites as they require the machinery of the host cell to replicate. Inhibition of host factors co-opted during active infection is a strategy to suppress viral replication and a potential pan antiviral therapy. To define the cellular proteins and processes required for a virus during infection is thus crucial to understanding the mechanisms of virally induced disease. In this report, we generated fully infectious tagged influenza viruses and used infection-based proteomics to identify pivotal arms of cellular signaling required for influenza virus growth and infectivity. Using mathematical modeling, genetic, and pharmacologic approaches, we revealed that modulation of Sec61-mediated cotranslational translocation selectively impaired glycoprotein proteostasis of influenza as well as HIV and dengue viruses, and led to inhibition of viral growth and infectivity. Thus, by studying virus-human protein-protein interactions in the context of active replication we have identified targetable host factors for broad-spectrum antiviral therapies. PMID:26789921

  14. Epidemiological and Virological Characterization of Influenza B Virus Infections

    PubMed Central

    Sharabi, Sivan; Drori, Yaron; Micheli, Michal; Friedman, Nehemya; Orzitzer, Sara; Bassal, Ravit; Glatman-Freedman, Aharona; Shohat, Tamar; Mendelson, Ella; Hindiyeh, Musa; Mandelboim, Michal

    2016-01-01

    While influenza A viruses comprise a heterogeneous group of clinically relevant influenza viruses, influenza B viruses form a more homogeneous cluster, divided mainly into two lineages: Victoria and Yamagata. This divergence has complicated seasonal influenza vaccine design, which traditionally contained two seasonal influenza A virus strains and one influenza B virus strain. We examined the distribution of the two influenza B virus lineages in Israel, between 2011–2014, in hospitalized and in non-hospitalized (community) influenza B virus-infected patients. We showed that influenza B virus infections can lead to hospitalization and demonstrated that during some winter seasons, both influenza B virus lineages circulated simultaneously in Israel. We further show that the influenza B virus Yamagata lineage was dominant, circulating in the county in the last few years of the study period, consistent with the anti-Yamagata influenza B virus antibodies detected in the serum samples of affected individuals residing in Israel in the year 2014. Interestingly, we found that elderly people were particularly vulnerable to Yamagata lineage influenza B virus infections. PMID:27533045

  15. Differentiation of infected and vaccinated animals (DIVA) using the NS1 protein of avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vaccination against avian influenza (AI) virus, a powerful tool for control of the disease, may result in issues related to surveillance programs and international trade of poultry and poultry products. The use of AI vaccination in poultry would have greater world-wide acceptance if a reliable test...

  16. TIM-1 Promotes Hepatitis C Virus Cell Attachment and Infection.

    PubMed

    Wang, Jing; Qiao, Luhua; Hou, Zhouhua; Luo, Guangxiang

    2017-01-15

    Human TIM and TAM family proteins were recently found to serve as phosphatidylserine (PS) receptors which promote infections by many different viruses, including dengue virus, West Nile virus, Ebola virus, Marburg virus, and Zika virus. In the present study, we provide substantial evidence demonstrating that TIM-1 is important for efficient infection by hepatitis C virus (HCV). The knockdown of TIM-1 expression significantly reduced HCV infection but not HCV RNA replication. Likewise, TIM-1 knockout in Huh-7.5 cells remarkably lowered HCV cell attachment and subsequent HCV infection. More significantly, the impairment of HCV infection in the TIM-1 knockout cells could be restored completely by ectopic expression of TIM-1 but not TIM-3 or TIM-4. Additionally, HCV infection and cell attachment were inhibited by PS but not by phosphatidylcholine (PC), demonstrating that TIM-1-mediated enhancement of HCV infection is PS dependent. The exposure of PS on the HCV envelope was confirmed by immunoprecipitation of HCV particles with a PS-specific monoclonal antibody. Collectively, these findings demonstrate that TIM-1 promotes HCV infection by serving as an attachment receptor for binding to PS exposed on the HCV envelope.

  17. Sofosbuvir treatment and hepatitis C virus infection

    PubMed Central

    Nakamura, Masato; Kanda, Tatsuo; Haga, Yuki; Sasaki, Reina; Wu, Shuang; Nakamoto, Shingo; Yasui, Shin; Arai, Makoto; Imazeki, Fumio; Yokosuka, Osamu

    2016-01-01

    Hepatitis C virus (HCV) infection is a serious problem worldwide. The use of interferon-based therapy has made HCV eradication challenging. The recent appearance of direct-acting antiviral agents (DAAs) has changed HCV therapy. Combining the use of DAAs with peginterferon and ribavirin has improved treatment efficacy. Furthermore, the combination of different orally administered DAAs has enabled interferon-free therapy with much higher efficacy and safety. In particular, sofosbuvir, a nucleotide-based NS5B inhibitor, prevents HCV RNA synthesis by acting as a “chain terminator”. Treatment with sofosbuvir has attained an extremely high rate of sustained virologic response. The current review summarizes the efficacy and safety of sofosbuvir therapy. PMID:26839641

  18. Transcriptional Profiling of the Immune Response to Marburg Virus Infection

    PubMed Central

    Yen, Judy; Caballero, Ignacio S.; Garamszegi, Sara; Malhotra, Shikha; Lin, Kenny; Hensley, Lisa; Goff, Arthur J.

    2015-01-01

    ABSTRACT Marburg virus is a genetically simple RNA virus that causes a severe hemorrhagic fever in humans and nonhuman primates. The mechanism of pathogenesis of the infection is not well understood, but it is well accepted that pathogenesis is appreciably driven by a hyperactive immune response. To better understand the overall response to Marburg virus challenge, we undertook a transcriptomic analysis of immune cells circulating in the blood following aerosol exposure of rhesus macaques to a lethal dose of Marburg virus. Using two-color microarrays, we analyzed the transcriptomes of peripheral blood mononuclear cells that were collected throughout the course of infection from 1 to 9 days postexposure, representing the full course of the infection. The response followed a 3-stage induction (early infection, 1 to 3 days postexposure; midinfection, 5 days postexposure; late infection, 7 to 9 days postexposure) that was led by a robust innate immune response. The host response to aerosolized Marburg virus was evident at 1 day postexposure. Analysis of cytokine transcripts that were overexpressed during infection indicated that previously unanalyzed cytokines are likely induced in response to exposure to Marburg virus and further suggested that the early immune response is skewed toward a Th2 response that would hamper the development of an effective antiviral immune response early in disease. Late infection events included the upregulation of coagulation-associated factors. These findings demonstrate very early host responses to Marburg virus infection and provide a rich data set for identification of factors expressed throughout the course of infection that can be investigated as markers of infection and targets for therapy. IMPORTANCE Marburg virus causes a severe infection that is associated with high mortality and hemorrhage. The disease is associated with an immune response that contributes to the lethality of the disease. In this study, we investigated how the

  19. Susceptibility of mouse macrophage J774 to dengue virus infection.

    PubMed

    Moreno-Altamirano, María M B; Sánchez-García, F Javier; Legorreta-Herrera, Martha; Aguilar-Carmona, Israel

    2007-01-01

    The aim of this study was to investigate whether the J774 mouse macrophage cell line could be used as an in vitro model for dengue virus infection (DENV). After 3 days, infection in J774 cells was assessed by detecting dengue virus non-structural protein 1 (NSP-1) production either by dot blot or indirect immunofluorescence assay (IFA) of saponine-permeabilized J774 cells and then confirmed by RT-PCR (171 bp product, corresponding to the DENV-2 core). Based on the presence of NSP-1 in infected but not in non-infected cells by both IFA and dot blot, as well as the amplification of a 171-bp DENV-2-specific RT-PCR product exclusively in the infected cells, the J774 cell line was found to be permissive for dengue virus infection. As far as we know, this is the first report that the J774 mouse macrophage cell line is infected with dengue virus and, thus, that it can be used as an alternative in vitro model for dengue virus infection studies. This finding could help to further elucidate the mechanisms involved in dengue virus infection and pathogenesis.

  20. Unfolded protein response in hepatitis C virus infection

    PubMed Central

    Chan, Shiu-Wan

    2014-01-01

    Hepatitis C virus (HCV) is a single-stranded, positive-sense RNA virus of clinical importance. The virus establishes a chronic infection and can progress from chronic hepatitis, steatosis to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The mechanisms of viral persistence and pathogenesis are poorly understood. Recently the unfolded protein response (UPR), a cellular homeostatic response to endoplasmic reticulum (ER) stress, has emerged to be a major contributing factor in many human diseases. It is also evident that viruses interact with the host UPR in many different ways and the outcome could be pro-viral, anti-viral or pathogenic, depending on the particular type of infection. Here we present evidence for the elicitation of chronic ER stress in HCV infection. We analyze the UPR signaling pathways involved in HCV infection, the various levels of UPR regulation by different viral proteins and finally, we propose several mechanisms by which the virus provokes the UPR. PMID:24904547

  1. Frog virus 3-like infections in aquatic amphibian communities.

    PubMed

    Duffus, A L J; Pauli, B D; Wozney, K; Brunetti, C R; Berrill, M

    2008-01-01

    Frog virus 3 (FV3) and FV3-like viruses, are members of the genus Ranavirus (family Iridoviridae), and they have been associated with infectious diseases that may be contributing to amphibian population declines. We examined the mode of transmission of an FV3-like virus, and potential hosts and reservoirs of the virus in a local amphibian community. Using the polymerase chain reaction to detect infected animals, we found an FV3-like virus in south-central Ontario, Canada, amphibian communities, where it infects sympatric amphibian species, including ranid and hylid tadpoles (Rana sylvatica, Hyla versicolor, and Pseudacris spp.), larval salamanders (Ambystoma spp.), and adult eastern-spotted newts (Notophthalmus viridescens). The high prevalence of FV3-like infections in caudate larvae suggests that salamanders are likely to be both hosts and reservoirs. In laboratory FV3 challenges of R. sylvatica, the rate of infection was dependent on the amount of virus to which the animals were exposed. In addition, although vertical transmission was suspected, horizontal transmission through exposure to infected pond water is the most likely route of infection in tadpoles. Based on our observations, a simple model of FV3/FV3-like virus transmission postulates that, in aquatic amphibian communities, transmission of the virus occurs between anuran and urodele species, with ambystomatid salamanders the most likely reservoir for the ranavirus in our study.

  2. A virus spreading model for cognitive radio networks

    NASA Astrophysics Data System (ADS)

    Hou, L.; Yeung, K. H.; Wong, K. Y.

    2012-12-01

    Since cognitive radio (CR) networks could solve the spectrum scarcity problem, they have drawn much research in recent years. Artificial intelligence(AI) is introduced into CRs to learn from and adapt to their environment. Nonetheless, AI brings in a new kind of attacks specific to CR networks. The most powerful one is a self-propagating AI virus. And no spreading properties specific to this virus have been reported in the literature. To fill this research gap, we propose a virus spreading model of an AI virus by considering the characteristics of CR networks and the behavior of CR users. Several important observations are made from the simulation results based on the model. Firstly, the time taken to infect the whole network increases exponentially with the network size. Based on this result, CR network designers could calculate the optimal network size to slow down AI virus propagation rate. Secondly, the anti-virus performance of static networks to an AI virus is better than dynamic networks. Thirdly, if the CR devices with the highest degree are initially infected, the AI virus propagation rate will be increased substantially. Finally, it is also found that in the area with abundant spectrum resource, the AI virus propagation speed increases notably but the variability of the spectrum does not affect the propagation speed much.

  3. Immune inhibition of virus release from herpes simplex virus-infected cells.

    PubMed

    Skinner, G R; Mushi, E Z; Whitney, J E

    By treatment of herpes simplex virus-infected cells with virus antiserum with or without complement, the yield of infectious extracellular virus was significantly reduced. This was shown to be due to an immune alteration of the cell membrane which inhibited release of virus particles from the infected cells and not due to neutralization; both type-common and type-specific antigens of herpes simplex virus were involved. The phenomenon was also evident with antisera directed against cell determinants. The experimental findings are presented and their significance in the immunological defense mechanisms of the body and in viral immunotherapy is discussed.

  4. Neonatal herpes simplex virus infection: epidemiology and treatment.

    PubMed

    James, Scott H; Kimberlin, David W

    2015-03-01

    Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) are highly prevalent viruses capable of establishing lifelong infection. Genital herpes in women of childbearing age represents a major risk for mother-to-child transmission (MTCT) of HSV infection, with primary and first-episode genital HSV infections posing the highest risk. The advent of antiviral therapy with parenteral acyclovir has led to significant improvement in neonatal HSV disease mortality. Further studies are needed to improve the clinician's ability to identify infants at increased risk for HSV infection and prevent MTCT, and to develop novel antiviral agents with increased efficacy in infants with HSV infection.

  5. Characteristics of human infection with avian influenza viruses and development of new antiviral agents

    PubMed Central

    Liu, Qiang; Liu, Dong-ying; Yang, Zhan-qiu

    2013-01-01

    Since 1997, several epizootic avian influenza viruses (AIVs) have been transmitted to humans, causing diseases and even deaths. The recent emergence of severe human infections with AIV (H7N9) in China has raised concerns about efficient interpersonal viral transmission, polygenic traits in viral pathogenicity and the management of newly emerging strains. The symptoms associated with viral infection are different in various AI strains: H5N1 and newly emerged H7N9 induce severe pneumonia and related complications in patients, while some H7 and H9 subtypes cause only conjunctivitis or mild respiratory symptoms. The virulence and tissue tropism of viruses as well as the host responses contribute to the pathogenesis of human AIV infection. Several preventive and therapeutic approaches have been proposed to combat AIV infection, including antiviral drugs such as M2 inhibitors, neuraminidase inhibitors, RNA polymerase inhibitors, attachment inhibitors and signal-transduction inhibitors etc. In this article, we summarize the recent progress in researches on the epidemiology, clinical features, pathogenicity determinants, and available or potential antivirals of AIV. PMID:24096642

  6. A case of consecutive infection with Zika virus and Chikungunya virus in Bora Bora, French Polynesia.

    PubMed

    Kutsuna, Satoshi; Kato, Yasuyuki; Nakayama, Eri; Taniguchi, Satoshi; Takasaki, Tomohiko; Yamamoto, Kei; Takeshita, Nozomi; Hayakawa, Kayoko; Kanagawa, Shuzo; Ohmagari, Norio

    2017-02-01

    Chikungunya fever (CHIK) and Zika virus (ZIKV) infection have similar endemic areas and clinical manifestations. We report a case of CHIK at 1 year after a ZIKV infection in Bora Bora (French Polynesia), which we diagnosed based on IgM to the CHIK virus and neutralizing antibodies to ZIKV.

  7. Absence of Active Hepatitis C Virus Infection in Human Immunodeficiency Virus Clinics in Zambia and Mozambique

    PubMed Central

    Wandeler, Gilles; Mulenga, Lloyd; Hobbins, Michael; Joao, Candido; Sinkala, Edford; Hector, Jonas; Aly, Musa; Chi, Benjamin H.; Egger, Matthias; Vinikoor, Michael J.

    2016-01-01

    Few studies have evaluated the prevalence of replicating hepatitis C virus (HCV) infection in sub-Saharan Africa. Among 1812 individuals infected with human immunodeficiency virus, no patient in rural Mozambique and 4 patients in urban Zambia were positive for anti-HCV antibodies. Of these, none had confirmed HCV replication. PMID:27047986

  8. Genetic strategy to prevent influenza virus infections in animals.

    PubMed

    Chen, Jianzhu; Chen, Steve C-Y; Stern, Patrick; Scott, Benjamin B; Lois, Carlos

    2008-02-15

    The natural reservoirs of influenza viruses are aquatic birds. After adaptation, avian viruses can acquire the ability to infect humans and cause severe disease. Because domestic poultry serves as a key link between the natural reservoir of influenza viruses and epidemics and pandemics in human populations, an effective measure to control influenza would be to eliminate or reduce influenza virus infection in domestic poultry. The development and distribution of influenza-resistant poultry represents a proactive strategy for controlling the origin of influenza epidemics and pandemics in both poultry and human populations. Recent developments in RNA interference and transgenesis in birds should facilitate the development of influenza-resistant poultry.

  9. Quantitation of human immunodeficiency virus type 1 infection kinetics.

    PubMed Central

    Dimitrov, D S; Willey, R L; Sato, H; Chang, L J; Blumenthal, R; Martin, M A

    1993-01-01

    Tissue culture infections of CD4-positive human T cells by human immunodeficiency virus type 1 (HIV-1) proceed in three stages: (i) a period following the initiation of an infection during which no detectable virus is produced; (ii) a phase in which a sharp increase followed by a peak of released progeny virions can be measured; and (iii) a final period when virus production declines. In this study, we have derived equations describing the kinetics of HIV-1 accumulation in cell culture supernatants during multiple rounds of infection. Our analyses indicated that the critical parameter affecting the kinetics of HIV-1 infection is the infection rate constant k = Inn/ti, where n is the number of infectious virions produced by one cell (about 10(2)) and ti is the time required for one complete cycle of virus infection (typically 3 to 4 days). Of particular note was our finding that the infectivity of HIV-1 during cell-to-cell transmission is 10(2) to 10(3) times greater than the infectivity of cell-free virus stocks, the inocula commonly used to initiate tissue culture infections. We also demonstrated that the slow infection kinetics of an HIV-1 tat mutant is not due to a longer replication time but reflects the small number of infectious particles produced per cycle. PMID:8445728

  10. Management of neonatal herpes simplex virus infection and exposure.

    PubMed

    Pinninti, Swetha G; Kimberlin, David W

    2014-05-01

    Neonatal herpes simplex virus (HSV) infections are rare but are associated with significant morbidity and mortality. Advances in diagnostic modalities to identify these infants, as well as the development of safe and effective antiviral therapy, have revolutionised the management of affected infants. This review will summarise the epidemiology of neonatal HSV infections and discuss the management of infants with HSV exposure and infection.

  11. Regulatory T Cells in Hepatitis B and C Virus Infections

    PubMed Central

    2016-01-01

    Hepatitis B virus (HBV) and hepatitis C virus (HCV) are hepatotropic viruses that establish chronic persistent infection by effectively escaping the host immune response and can cause immune-mediated liver injury. It has recently become apparent that regulatory T (Treg) cells, specifically CD4+CD25+Foxp3+ Treg cells, modulate viral diseases by suppressing antiviral immune responses and regulating inflammatory host injury. The roles of Treg cells in HBV and HCV infections range from suppressing antiviral T cell responses to protecting the liver from immune-mediated damage. This review describes Treg cells and subpopulations and focuses on the roles of these cells in HBV and HCV infections. PMID:28035208

  12. Failure of transmission of low-pathogenic avian influenza virus between Mallards and freshwater snails: an experimental evaluation.

    PubMed

    Oesterle, Paul T; Huyvaert, Kathryn P; Orahood, Darcy; Mooers, Nicole; Sullivan, Heather; Franklin, Alan B; Root, J Jeffrey

    2013-10-01

    In aquatic bird populations, the ability of avian influenza (AI) viruses to remain infectious in water for extended periods provides a mechanism that allows viral transmission to occur long after shedding birds have left the area. However, this also exposes other aquatic organisms, including freshwater invertebrates, to AI viruses. Previous researchers found that AI viral RNA can be sequestered in snail tissues. Using an experimental approach, we determined whether freshwater snails (Physa acuta and Physa gyrina) can infect waterfowl with AI viruses by serving as a means of transmission between infected and naïve waterfowl via ingestion. In our first experiment, we exposed 20 Physa spp. snails to an AI virus (H3N8) and inoculated embryonated specific pathogen-free (SPF) chicken eggs with the homogenized snail tissues. Sequestered AI viruses remain infectious in snail tissues; 10% of the exposed snail tissues infected SPF eggs. In a second experiment, we exposed snails to water contaminated with feces of AI virus-inoculated Mallards (Anas platyrhynchos) to evaluate whether ingestion of exposed freshwater snails was an alternate route of AI virus transmission to waterfowl. None of the immunologically naïve Mallards developed an infection, indicating that transmission via ingestion likely did not occur. Our results suggest that this particular trophic interaction may not play an important role in the transmission of AI viruses in aquatic habitats.

  13. Virus-Bacteria Interactions: An Emerging Topic in Human Infection

    PubMed Central

    Almand, Erin A.; Moore, Matthew D.; Jaykus, Lee-Ann

    2017-01-01

    Bacteria and viruses often occupy the same niches, however, interest in their potential collaboration in promoting wellness or disease states has only recently gained traction. While the interaction of some bacteria and viruses is well characterized (e.g., influenza virus), researchers are typically more interested in the location of the infection than the manner of cooperation. There are two overarching types of bacterial-virus disease causing interactions: direct interactions that in some way aid the viruses, and indirect interactions aiding bacteria. The virus-promoting direct interactions occur when the virus exploits a bacterial component to facilitate penetration into the host cell. Conversely, indirect interactions result in increased bacterial pathogenesis as a consequence of viral infection. Enteric viruses mainly utilize the direct pathway, while respiratory viruses largely affect bacteria in an indirect fashion. This review focuses on some key examples of how virus-bacteria interactions impact the infection process across the two organ systems, and provides evidence supporting this as an emerging theme in infectious disease. PMID:28335562

  14. Virus-Bacteria Interactions: An Emerging Topic in Human Infection.

    PubMed

    Almand, Erin A; Moore, Matthew D; Jaykus, Lee-Ann

    2017-03-21

    Bacteria and viruses often occupy the same niches, however, interest in their potential collaboration in promoting wellness or disease states has only recently gained traction. While the interaction of some bacteria and viruses is well characterized (e.g., influenza virus), researchers are typically more interested in the location of the infection than the manner of cooperation. There are two overarching types of bacterial-virus disease causing interactions: direct interactions that in some way aid the viruses, and indirect interactions aiding bacteria. The virus-promoting direct interactions occur when the virus exploits a bacterial component to facilitate penetration into the host cell. Conversely, indirect interactions result in increased bacterial pathogenesis as a consequence of viral infection. Enteric viruses mainly utilize the direct pathway, while respiratory viruses largely affect bacteria in an indirect fashion. This review focuses on some key examples of how virus-bacteria interactions impact the infection process across the two organ systems, and provides evidence supporting this as an emerging theme in infectious disease.

  15. Prevalence of Hepatitis Virus Infections in an Institution for Persons with Developmental Disabilities.

    ERIC Educational Resources Information Center

    Woodruff, Bradley A.; Vazquez, Elizabeth

    2002-01-01

    A study involving 1,235 residents of Sonoma Developmental Center found 3 residents had hepatitis C virus infections, and 633 had past or current hepatitis B virus infections. The prevalence of hepatitis B virus infection rose rapidly with longer residence in institutions. Hepatitis A virus infection had occurred in 494 residents. (Contains…

  16. Infective substructures of measles virus from acutely and persistently infected cells.

    PubMed Central

    Rozenblatt, S; Koch, T; Pinhasi, O; Bratosin, S

    1979-01-01

    Ribonucleoprotein from cells acutely or persistently infected with measles virus were shown to be infectious by the calcium phosphate technique. Very little or no infectivity was obtained when calcium phosphate precipitation was omitted. Electron microscopy showed that the majority of ribonucleoprotein structures isolated from acutely infected cells were folded, whereas those from persistently infected cells were linear in appearance. Images PMID:120450

  17. Studying NK cell responses to ectromelia virus infections in mice.

    PubMed

    Fang, Min; Sigal, Luis

    2010-01-01

    Here we describe methods for the in vivo study of antiviral NK cell responses using the mouse Orthopoxvirus ectromelia virus as a model, the agent of mousepox. The methods include those specific for the preparation and use of ectromelia virus such as the production of virus stocks in tissue culture and in live mice, the purification of virus stocks, the titration of virus stocks and virus loads in organs, and the infection of mice. The chapter also includes methods for the specific study of NK cell responses in infected mice such as the preparation of organs (lymph nodes, spleen, and liver) for analysis, the study of NK cell responses by flow cytometry, the adoptive transfer of NK cells, the measurement of NK cell cytolytic activity ex vivo and in vivo, and the determination of NK cell proliferation by bromodeoxyuridine loading or by dilution of carboxyfluorescein diacetate succinimidyl ester (CFSE).

  18. The Impact of Wolbachia on Virus Infection in Mosquitoes

    PubMed Central

    Johnson, Karyn N.

    2015-01-01

    Mosquito-borne viruses such as dengue, West Nile and chikungunya viruses cause significant morbidity and mortality in human populations. Since current methods are not sufficient to control disease occurrence, novel methods to control transmission of arboviruses would be beneficial. Recent studies have shown that virus infection and transmission in insects can be impeded by co-infection with the bacterium Wolbachia pipientis. Wolbachia is a maternally inherited endosymbiont that is commonly found in insects, including a number of mosquito vector species. In Drosophila, Wolbachia mediates antiviral protection against a broad range of RNA viruses. This discovery pointed to a potential strategy to interfere with mosquito transmission of arboviruses by artificially infecting mosquitoes with Wolbachia. This review outlines research on the prevalence of Wolbachia in mosquito vector species and the impact of antiviral effects in both naturally and artificially Wolbachia-infected mosquitoes. PMID:26556361

  19. The control of bovine viral diarrhoea virus infection.

    PubMed

    Harkness, J W

    1987-01-01

    In this paper, current ideas concerning the epidemiology of BVD virus infection are reviewed briefly, together with its possible economic implications. The different types of control strategies are considered. Problems associated with vaccination are discussed.

  20. The Impact of Wolbachia on Virus Infection in Mosquitoes.

    PubMed

    Johnson, Karyn N

    2015-11-04

    Mosquito-borne viruses such as dengue, West Nile and chikungunya viruses cause significant morbidity and mortality in human populations. Since current methods are not sufficient to control disease occurrence, novel methods to control transmission of arboviruses would be beneficial. Recent studies have shown that virus infection and transmission in insects can be impeded by co-infection with the bacterium Wolbachia pipientis. Wolbachia is a maternally inherited endosymbiont that is commonly found in insects, including a number of mosquito vector species. In Drosophila, Wolbachia mediates antiviral protection against a broad range of RNA viruses. This discovery pointed to a potential strategy to interfere with mosquito transmission of arboviruses by artificially infecting mosquitoes with Wolbachia. This review outlines research on the prevalence of Wolbachia in mosquito vector species and the impact of antiviral effects in both naturally and artificially Wolbachia-infected mosquitoes.

  1. Protection of poultry from highly pathogenic avian influenza with multivalent virus-like particle vaccines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza (AI) viruses, especially H5 subtypes, cause widespread morbidity and mortality in domestic and wild bird populations. Dissemination of AI results primarily from the movement of the virus through infected poultry and poultry products, but migratory birds have also served as secondary...

  2. Alcohol use disorder and its impact on chronic hepatitis C virus and human immunodeficiency virus infections

    PubMed Central

    Fuster, Daniel; Sanvisens, Arantza; Bolao, Ferran; Rivas, Inmaculada; Tor, Jordi; Muga, Robert

    2016-01-01

    Alcohol use disorder (AUD) and hepatitis C virus (HCV) infection frequently co-occur. AUD is associated with greater exposure to HCV infection, increased HCV infection persistence, and more extensive liver damage due to interactions between AUD and HCV on immune responses, cytotoxicity, and oxidative stress. Although AUD and HCV infection are associated with increased morbidity and mortality, HCV antiviral therapy is less commonly prescribed in individuals with both conditions. AUD is also common in human immunodeficiency virus (HIV) infection, which negatively impacts proper HIV care and adherence to antiretroviral therapy, and liver disease. In addition, AUD and HCV infection are also frequent within a proportion of patients with HIV infection, which negatively impacts liver disease. This review summarizes the current knowledge regarding pathological interactions of AUD with hepatitis C infection, HIV infection, and HCV/HIV co-infection, as well as relating to AUD treatment interventions in these individuals. PMID:27872681

  3. Pathogenesis and Transmission of Kilham Rat Virus Infection in Rats

    PubMed Central

    Novotny, James F.; Hetrick, Frank M.

    1970-01-01

    The Kilham rat virus (RV) was found to produce mortality in newborn rats after intracerebral, intravenous, or subcutaneous administration of virus. Both infectious virus and viral hemagglutinins were detected in a variety of tissues and in the blood and urine of experimentally infected rats. Contact control rats housed with infected littermates did not develop disease but did produce antibody to RV. Horizontal virus transmission was also evidenced by the seroconversion of antibody-negative mothers whose litters were infected with RV. The level of maternal antibody was found to be the determining factor in the susceptibility or refractiveness of newborn rats to RV infection. If the mother had no detectable hemagglutination-inhibiting (HI) antibody titer (less than 10) or a low antibody titer (10 or 20), her offspring were highly susceptible to RV. However, the litters of rats with HI titers of 40 or greater were afforded protection when challenged with RV; the higher the maternal antibody level the more solid was the protection conferred. Vertical transmission of RV was also demonstrated. Litters born of mothers infected with RV several days before delivery died within 7 to 9 days of a disease identical to that seen in infected newborns and virus was recovered from a variety of tissues. Results of mother-litter exchange experiments also indicated vertical transmission (rather than transmission through milk) occurs, since litters of infected mothers developed the disease when nursed by normal mothers, whereas litters of normal mothers remained normal although they were nursed by infected mothers. PMID:16557835

  4. [Immune response in the pathogenesis of hepatitis C virus infection].

    PubMed

    Chalupa, P; Holub, M; Davidová, A; Arientová, S; Beran, O

    2015-10-01

    The pathogenesis of hepatitis C virus (HCV) infection is regulated by the host immunity and several metabolic factors affecting liver metabolism, including oxidative stress, insulin resistance, and hepatic steatosis. Both innate and adaptive immunity play an important role in HCV infection. Cytotoxic lymphocytes have a crucial role in viral eradication or viral persistence. Major cause of viral persistence during HCV infection could be the development of a weak antiviral immune response to the viral antigens, with corresponding inability to eradicate infected cells.

  5. The Human Immunodeficiency Virus: Infectivity and Mechanisms of Pathogenesis.

    ERIC Educational Resources Information Center

    Fauci, Anthony S.

    1988-01-01

    Discusses how the infection of the human immunodeficiency virus (HIV) results in a profound immunosuppression due predominantly to a selective depletion of helper/inducer T lymphocytes that express the receptor for the virus, as well as neuropsychiatric abnormalities in the brain. (TW)

  6. Zucchini tigre mosaic virus infection of cucurbits in Florida

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Zucchini tigre mosaic virus (ZTMV) was identified infecting cucurbits in Florida in 2002 and again in 2015. This is the first report of ZTMV in the U.S. This report provides an overview of this emerging virus for growers, extension workers, crop consultants, and research and regulatory scientists....

  7. Influenza virus infection in guinea pigs raised as livestock, Ecuador.

    PubMed

    Leyva-Grado, Victor H; Mubareka, Samira; Krammer, Florian; Cárdenas, Washington B; Palese, Peter

    2012-07-01

    To determine whether guinea pigs are infected with influenza virus in nature, we conducted a serologic study in domestic guinea pigs in Ecuador. Detection of antibodies against influenza A and B raises the question about the role of guinea pigs in the ecology and epidemiology of influenza virus in the region.

  8. The naming of Potato virus Y strains infecting potato

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Potato virus Y (PVY) strain groups are based on host-response and resistance-gene interactions. The strain groups PVYO, PVYC and PVYN are well-established for the isolates infecting potato in the field. A switch in the emphasis from host response to nucleotide sequence differences in the virus genom...

  9. West Nile virus infections in humans--focus on Greece.

    PubMed

    Papa, Anna

    2013-10-01

    West Nile virus is a mosquito-borne flavivirus causing to humans a variety of symptoms, from asymptomatic or mild infection, to severe, and often fatal, infection of the central nervous system. The present review aims to describe the main clinical characteristics of the disease, to provide the recent epidemiological data, including those from the recent outbreaks in Greece, and to discuss the environmental factors which might play a role in the virus emergence and its wider dispersal.

  10. Correlation between Virus Replication and Antibody Responses in Macaques following Infection with Pandemic Influenza A Virus

    PubMed Central

    Koopman, Gerrit; Dekking, Liesbeth; Mortier, Daniëlla; Nieuwenhuis, Ivonne G.; van Heteren, Melanie; Kuipers, Harmjan; Remarque, Edmond J.; Radošević, Katarina; Bogers, Willy M. J. M.

    2015-01-01

    ABSTRACT Influenza virus infection of nonhuman primates is a well-established animal model for studying pathogenesis and for evaluating prophylactic and therapeutic intervention strategies. However, usually a standard dose is used for the infection, and there is no information on the relation between challenge dose and virus replication or the induction of immune responses. Such information is also very scarce for humans and largely confined to evaluation of attenuated virus strains. Here, we have compared the effect of a commonly used dose (4 × 106 50% tissue culture infective doses) versus a 100-fold-higher dose, administered by intrabronchial installation, to two groups of 6 cynomolgus macaques. Animals infected with the high virus dose showed more fever and had higher peak levels of gamma interferon in the blood. However, virus replication in the trachea was not significantly different between the groups, although in 2 out of 6 animals from the high-dose group it was present at higher levels and for a longer duration. The virus-specific antibody response was not significantly different between the groups. However, antibody enzyme-linked immunosorbent assay, virus neutralization, and hemagglutination inhibition antibody titers correlated with cumulative virus production in the trachea. In conclusion, using influenza virus infection in cynomolgus macaques as a model, we demonstrated a relationship between the level of virus production upon infection and induction of functional antibody responses against the virus. IMPORTANCE There is only very limited information on the effect of virus inoculation dose on the level of virus production and the induction of adaptive immune responses in humans or nonhuman primates. We found only a marginal and variable effect of virus dose on virus production in the trachea but a significant effect on body temperature. The induction of functional antibody responses, including virus neutralization titer, hemagglutination inhibition

  11. Easy and Rapid Detection of Mumps Virus by Live Fluorescent Visualization of Virus-Infected Cells

    PubMed Central

    Takahashi, Tadanobu; Agarikuchi, Takashi; Kurebayashi, Yuuki; Shibahara, Nona; Suzuki, Chihiro; Kishikawa, Akiko; Fukushima, Keijo; Takano, Maiko; Suzuki, Fumie; Wada, Hirohisa; Otsubo, Tadamune; Ikeda, Kiyoshi; Minami, Akira; Suzuki, Takashi

    2015-01-01

    Mumps viruses show diverse cytopathic effects (CPEs) of infected cells and viral plaque formation (no CPE or no plaque formation in some cases) depending on the viral strain, highlighting the difficulty in mumps laboratory studies. In our previous study, a new sialidase substrate, 2-(benzothiazol-2-yl)-4-bromophenyl 5-acetamido-3,5-dideoxy-α-D-glycero-D-galacto-2-nonulopyranosidonic acid (BTP3-Neu5Ac), was developed for visualization of sialidase activity. BTP3-Neu5Ac can easily and rapidly perform histochemical fluorescent visualization of influenza viruses and virus-infected cells without an antiviral antibody and cell fixation. In the present study, the potential utility of BTP3-Neu5Ac for rapid detection of mumps virus was demonstrated. BTP3-Neu5Ac could visualize dot-blotted mumps virus, virus-infected cells, and plaques (plaques should be called focuses due to staining of infected cells in this study), even if a CPE was not observed. Furthermore, virus cultivation was possible by direct pick-up from a fluorescent focus. In conventional methods, visible appearance of the CPE and focuses often requires more than 6 days after infection, but the new method with BTP3-Neu5Ac clearly visualized infected cells after 2 days and focuses after 4 days. The BTP3-Neu5Ac assay is a precise, easy, and rapid assay for confirmation and titration of mumps virus. PMID:26629699

  12. Recombinant vesicular stomatitis virus-based vaccines against Ebola and Marburg virus infections.

    PubMed

    Geisbert, Thomas W; Feldmann, Heinz

    2011-11-01

    The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with a high mortality rate in humans and nonhuman primates. Among the most-promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Importantly, a single injection of blended rVSV-based filovirus vaccines was shown to completely protect nonhuman primates against Marburg virus and 3 different species of Ebola virus. These rVSV-based vaccines have also shown utility when administered as a postexposure treatment against filovirus infections, and a rVSV-based Ebola virus vaccine was recently used to treat a potential laboratory exposure. Here, we review the history of rVSV-based vaccines and pivotal animal studies showing their utility in combating Ebola and Marburg virus infections.

  13. Experimental St. Louis encephalitis virus infection of sloths and cormorants.

    PubMed

    Seymour, C; Kramer, L D; Peralta, P H

    1983-07-01

    Experimental infection of 11 Bradypus variegatus and Choloepus hoffmanni sloths with St. Louis encephalitis (SLE) virus produced detectable viremias of seven to 27 (median 13) days duration and maximum titers of 2.7 to 6.5 (median 5.1) log10 median suckling mouse intracranial lethal doses (SMicLD50) per ml. Experimental SLE viremia onset was delayed and maximum titer depressed in two sloths concurrently infected with naturally acquired viruses. SLE viremias in four experimentally inoculated cormorants Phalacrocorax olivaceus were shorter, and of equal or lower titer, than in sloths. Colonized Culex pipiens quinquefasciatus mosquitoes were infected by feeding on sloths circulating at least 4.8 log10 SMicLD50 of SLE virus per ml, and subsequently transmitted the infection to mice and chicks. An uninoculated baby Bradypus became infected by contact transmission from its mother. The antibody response of sloths to SLE virus was slow, being undetectable until several weeks post-inoculation. However, both sloth species developed high and long-lasting neutralizing and hemagglutination-inhibition antibody titers. The complement-fixation antibody response in Bradypus was lower and slower to develop than in Choloepus. Sloths with naturally acquired SLE virus antibody did not become detectably viremic after experimental inoculation. Neither sloths nor cormorants become overly ill from SLE virus infection.

  14. Cell-to-cell infection by HIV contributes over half of virus infection.

    PubMed

    Iwami, Shingo; Takeuchi, Junko S; Nakaoka, Shinji; Mammano, Fabrizio; Clavel, François; Inaba, Hisashi; Kobayashi, Tomoko; Misawa, Naoko; Aihara, Kazuyuki; Koyanagi, Yoshio; Sato, Kei

    2015-10-06

    Cell-to-cell viral infection, in which viruses spread through contact of infected cell with surrounding uninfected cells, has been considered as a critical mode of virus infection. However, since it is technically difficult to experimentally discriminate the two modes of viral infection, namely cell-free infection and cell-to-cell infection, the quantitative information that underlies cell-to-cell infection has yet to be elucidated, and its impact on virus spread remains unclear. To address this fundamental question in virology, we quantitatively analyzed the dynamics of cell-to-cell and cell-free human immunodeficiency virus type 1 (HIV-1) infections through experimental-mathematical investigation. Our analyses demonstrated that the cell-to-cell infection mode accounts for approximately 60% of viral infection, and this infection mode shortens the generation time of viruses by 0.9 times and increases the viral fitness by 3.9 times. Our results suggest that even a complete block of the cell-free infection would provide only a limited impact on HIV-1 spread.

  15. Infection of Mosquito Cells (C6/36) by Dengue-2 Virus Interferes with Subsequent Infection by Yellow Fever Virus.

    PubMed

    Abrao, Emiliana Pereira; da Fonseca, Benedito Antônio Lopes

    2016-02-01

    Dengue is one of the most important diseases caused by arboviruses in the world. Yellow fever is another arthropod-borne disease of great importance to public health that is endemic to tropical regions of Africa and the Americas. Both yellow fever and dengue viruses are flaviviruses transmitted by Aedes aegypti mosquitoes, and then, it is reasonable to consider that in a given moment, mosquito cells could be coinfected by both viruses. Therefore, we decided to evaluate if sequential infections of dengue and yellow fever viruses (and vice-versa) in mosquito cells could affect the virus replication patterns. Using immunofluorescence and real-time PCR-based replication assays in Aedes albopictus C6/36 cells with single or sequential infections with both viruses, we demonstrated the occurrence of viral interference, also called superinfection exclusion, between these two viruses. Our results show that this interference pattern is particularly evident when cells were first infected with dengue virus and subsequently with yellow fever virus (YFV). Reduction in dengue virus replication, although to a lower extent, was also observed when C6/36 cells were initially infected with YFV followed by dengue virus infection. Although the importance that these findings have on nature is unknown, this study provides evidence, at the cellular level, of the occurrence of replication interference between dengue and yellow fever viruses and raises the question if superinfection exclusion could be a possible explanation, at least partially, for the reported lack of urban yellow fever occurrence in regions where a high level of dengue transmission occurs.

  16. Co-infection and disease severity of Ohio Maize dwarf mosaic virus and Maize chlorotic dwarf virus strains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two major maize viruses have been reported in the United States: Maize dwarf mosaic virus (MDMV) and Maize chlorotic dwarf virus (MCDV). These viruses co-occur in regions where maize is grown such that co-infections are likely. Co-infection of different strains of MCDV is also observed frequently...

  17. First case of imported Zika virus infection in Spain.

    PubMed

    Bachiller-Luque, Pablo; Domínguez-Gil González, Marta; Álvarez-Manzanares, Jesús; Vázquez, Ana; De Ory, Fernando; Sánchez-Seco Fariñas, M Paz

    2016-04-01

    We report a case of Zika virus (ZIKV) infection in a patient with diarrhea, fever, synovitis, non-purulent conjunctivitis, and with discreet retro-orbital pain, after returning from Colombia in January 2016. The patient referred several mosquito bites. Presence of ZIKV was detected by PCR (polymerase chain reaction) in plasma. Rapid microbiological diagnosis of ZIKV infection is needed in European countries with circulation of its vector, in order to avoid autochthonous circulation. The recent association of ZIKV infection with abortion and microcephaly, and a Guillain-Barré syndrome highlights the need for laboratory differentiation of ZIKV from other virus infection. Women with potential risk for Zika virus infection who are pregnant or planning to become pregnant must mention that fact during prenatal visits in order to be evaluated and properly monitored.

  18. Attenuation of Dengue Virus Infection by Adeno-Associated Virus-Mediated siRNA Delivery

    DTIC Science & Technology

    2004-08-09

    Pharmingen) for 7 days prior to infection with DEN. Blocking dengue virus infection in vitro 1 × 105 Vero cells or DCs were seeded into six-well tissue...essential for dengue pathogenesis in the human host. In this study, we also utilized peripheral blood iDCs as a cell model to test our AAV system. Similar to...attenu- ate DEN infection. List of abbreviations AAV, adeno-associated virus; DCs, dendritic cells ; DEN, dengue virus; DHF/DSS, dengue hemorrhagic fever

  19. Natural infection of turkeys by infectious laryngotracheitis virus.

    PubMed

    Portz, Cristiana; Beltrão, Nilzane; Furian, Thales Quedi; Júnior, Alfredo Bianco; Macagnan, Marisa; Griebeler, Josiane; Lima Rosa, Carlos André Veiga; Colodel, Edson Moleta; Driemeier, David; Back, Alberto; Barth Schatzmayr, Ortrud Monika; Canal, Cláudio Wageck

    2008-09-18

    The infectious laryngotracheitis virus (ILTV) is an important respiratory pathogen of chickens that also infects pheasants and peafowl. Epidemiologically non-related commercial turkey flocks with clinical signs such as tracheitis, swollen sinuses, conjunctivitis and expectoration of bloody mucus were examined for the presence of the virus. Laboratory ILTV detection was performed by virus isolation in embryonated eggs and cell cultures, PCR and sequencing of amplification products, histopathology, indirect immunofluorescence and electron microscopy. One ILTV turkey isolate was also experimentally inoculated into susceptible chickens and turkeys, reproducing a mild respiratory disease. This is the first description of natural infections with ILTV in turkeys.

  20. Persistent infection of macaques with simian-human immunodeficiency viruses.

    PubMed Central

    Li, J T; Halloran, M; Lord, C I; Watson, A; Ranchalis, J; Fung, M; Letvin, N L; Sodroski, J G

    1995-01-01

    Chimeric simian-human immunodeficiency viruses (SHIV) containing the human immunodeficiency virus type 1 (HIV-1) tat, rev, env, and, in some cases, vpu genes were inoculated into eight cynomolgus monkeys. Viruses could be consistently recovered from the CD8-depleted peripheral blood lymphocytes of all eight animals for at least 2 months. After this time, virus isolation varied among the animals, with viruses continuing to be isolated from some animals beyond 600 days after inoculation. The level of viral RNA in plasma during acute infection and the frequency of virus isolation after the initial 2-month period were higher for the Vpu-positive viruses. All of the animals remained clinically healthy, and the absolute numbers of CD4-positive lymphocytes were stable. Antibodies capable of neutralizing HIV-1 were generated at high titers in animals exhibiting the greatest consistency of virus isolation. Strain-specific HIV-1-neutralizing antibodies were initially elicited, and then more broadly neutralizing antibodies were elicited. env sequences from two viruses isolated more than a year after infection were analyzed. In the Vpu-negative SHIV, for which virus loads were lower, a small amount of env variation, which did not correspond to that found in natural HIV-1 variants, was observed. By contrast, in the Vpu-positive virus, which was consistently isolated from the host animal, extensive variation of the envelope glycoproteins in the defined variable gp120 regions was observed. Escape from neutralization by CD4 binding site monoclonal antibodies was observed for the viruses with the latter envelope glycoproteins, and the mechanism of escape appears to involve decreased binding of the antibody to the monomeric gp120 glycoproteins. The consistency with which SHIV infection of cynomolgus monkeys is initiated and the similarities in the neutralizing antibody response to SHIV and HIV-1 support the utility of this model system for the study of HIV-1 prophylaxis. PMID

  1. Experimental evidence of hepatitis A virus infection in pigs.

    PubMed

    Song, Young-Jo; Park, Woo-Jung; Park, Byung-Joo; Kwak, Sang-Woo; Kim, Yong-Hyeon; Lee, Joong-Bok; Park, Seung-Yong; Song, Chang-Seon; Lee, Sang-Won; Seo, Kun-Ho; Kang, Young-Sun; Park, Choi-Kyu; Song, Jae-Young; Choi, In-Soo

    2016-04-01

    Hepatitis A virus (HAV) is the leading cause of acute viral hepatitis worldwide, with HAV infection being restricted to humans and nonhuman primates. In this study, HAV infection status was serologically determined in domestic pigs and experimental infections of HAV were attempted to verify HAV infectivity in pigs. Antibodies specific to HAV or HAV-like agents were detected in 3.5% of serum samples collected from pigs in swine farms. When the pigs were infected intravenously with 2 × 10(5) 50% tissue culture infectious dose (TCID50 ) of HAV, shedding of the virus in feces, viremia, and seroconversion were detected. In pigs orally infected with the same quantity of HAV, viral shedding was detected only in feces. HAV genomic RNA was detected in the liver and bile of intravenously infected pigs, but only in the bile of orally infected pigs. In further experiments, pigs were intravenously infected with 6 × 10(5) TCID50 of HAV. Shedding of HAV in feces, along with viremia and seroconversion, were confirmed in infected pigs but not in sentinel pigs. HAV genomic RNA was detected in the liver, bile, spleen, lymph node, and kidney of the infected pigs. HAV antigenomic RNA was detected in the spleen of one HAV-infected pig, suggesting HAV replication in splenic cells. Infiltration of inflammatory cells was observed in the livers of infected pigs but not in controls. This is the first experimental evidence to demonstrate that human HAV strains can infect pigs.

  2. Reduced Risk of Disease During Postsecondary Dengue Virus Infections

    PubMed Central

    Olkowski, Sandra; Forshey, Brett M.; Morrison, Amy C.; Rocha, Claudio; Vilcarromero, Stalin; Halsey, Eric S.; Kochel, Tadeusz J.; Scott, Thomas W.; Stoddard, Steven T.

    2013-01-01

    Background. Antibodies induced by infection with any 1 of 4 dengue virus (DENV) serotypes (DENV-1–4) may influence the clinical outcome of subsequent heterologous infections. To quantify potential cross-protective effects, we estimated disease risk as a function of DENV infection, using data from longitudinal studies performed from September 2006 through February 2011 in Iquitos, Peru, during periods of DENV-3 and DENV-4 transmission. Methods. DENV infections before and during the study period were determined by analysis of serial serum samples with virus neutralization tests. Third and fourth infections were classified as postsecondary infections. Dengue fever cases were detected by door-to-door surveillance for acute febrile illness. Results. Among susceptible participants, 39% (420/1077) and 53% (1595/2997) seroconverted to DENV-3 and DENV-4, respectively. Disease was detected in 7% of DENV-3 infections and 10% of DENV-4 infections. Disease during postsecondary infections was reduced by 93% for DENV-3 and 64% for DENV-4, compared with primary and secondary infections. Despite lower disease rates, postsecondary infections constituted a significant proportion of apparent infections (14% [for DENV-3 infections], 45% [for DENV-4 infections]). Conclusions. Preexisting heterotypic antibodies markedly reduced but did not eliminate the risk of disease in this study population. These results improve understanding of how preinfection history can be associated with dengue outcomes and DENV transmission dynamics. PMID:23776195

  3. Nanodiscs as a therapeutic delivery agent: inhibition of respiratory syncytial virus infection in the lung.

    PubMed

    Numata, Mari; Grinkova, Yelena V; Mitchell, James R; Chu, Hong Wei; Sligar, Stephen G; Voelker, Dennis R

    2013-01-01

    There is increasing interest in the application of nanotechnology to solve the difficult problem of therapeutic administration of pharmaceuticals. Nanodiscs, composed of a stable discoidal lipid bilayer encircled by an amphipathic membrane scaffold protein that is an engineered variant of the human Apo A-I constituent of high-density lipoproteins, have been a successful platform for providing a controlled lipid composition in particles that are especially useful for investigating membrane protein structure and function. In this communication, we demonstrate that nanodiscs are effective in suppressing respiratory syncytial viral (RSV) infection both in vitro and in vivo when self-assembled with the minor pulmonary surfactant phospholipid palmitoyloleoylphosphatidylglycerol (POPG). Preparations of nanodiscs containing POPG (nPOPG) antagonized interleukin-8 production from Beas2B epithelial cells challenged by RSV infection, with an IC50 of 19.3 μg/mL. In quantitative in vitro plaque assays, nPOPG reduced RSV infection by 93%. In vivo, nPOPG suppressed inflammatory cell infiltration into the lung, as well as IFN-γ production in response to RSV challenge. nPOPG also completely suppressed the histopathological changes in lung tissue elicited by RSV and reduced the amount of virus recovered from lung tissue by 96%. The turnover rate of nPOPG was estimated to have a halftime of 60-120 minutes (m), based upon quantification of the recovery of the human Apo A-I constituent. From these data, we conclude that nPOPG is a potent antagonist of RSV infection and its inflammatory sequelae both in vitro and in vivo.

  4. Detection of Aichi virus with antibody targeting of conserved viral protein 1 epitope.

    PubMed

    Chen, Yao-Shen; Chen, Bao-Chen; Lin, You-Sheng; Chang, Jenn-Tzong; Huang, Tsi-Shu; Chen, Jih-Jung; Chang, Tsung-Hsien

    2013-10-01

    Aichi virus (AiV) is an emerging single-stranded, positive-sense, non-enveloped RNA virus in the Picornaviridae that causes acute gastroenteritis in humans. The first case of AiV infection in Taiwan was diagnosed in a human neonate with enterovirus-associated symptoms; the virus was successfully isolated and propagated. To establish a method to detect AiV, we analyzed the antigen epitope and generated a polyclonal antibody against AiV viral protein 1 (VP1). This peptide-purified anti-AiV VP1 antibody showed high specificity against AiV VP1 without cross-reaction to nine other tested strains of Picornaviruses. The anti-AiV VP1 antibody was used in immunofluorescence analysis, immunoblotting, and enzyme-linked immunosorbent assay to elucidate the cell tropism and replication kinetics of AiV. Use of the anti-AiV VP1 antibody also revealed AiV infection restriction with interferon type I and polyI/C antiviral treatment. The AiV infection and detection system may provide an in vitro platform for AiV virology study.

  5. Characteristics of Mild Dengue Virus Infection in Thai Children

    PubMed Central

    Yoon, In-Kyu; Srikiatkhachorn, Anon; Hermann, Laura; Buddhari, Darunee; Scott, Thomas W.; Jarman, Richard G.; Aldstadt, Jared; Nisalak, Ananda; Thammapalo, Suwich; Bhoomiboonchoo, Piraya; Mammen, Mammen P.; Green, Sharone; Gibbons, Robert V.; Endy, Timothy P.; Rothman, Alan L.

    2013-01-01

    A four-year longitudinal cohort and geographic cluster study in rural Thailand was conducted to characterize the clinical spectrum of dengue virus (DENV) infection. Symptomatic DENV infections in the cohort were detected by active school absence–based surveillance that triggered cluster investigations around ill cohort children. Data from 189 cohort children with symptomatic DENV infection and 126 contact children in the clusters with DENV infection were analyzed. Of infected contacts, only 19% were asymptomatic; 81% were symptomatic, but only 65.9% reported fever. Symptom-based case definitions were unreliable for diagnosis. Symptomatic infections in contacts were milder with lower DENV RNA levels than the cohort. Infections in contacts with fever history were more likely to have detectable DENV RNA than infections without fever history. Mild infections identified by cluster investigations account for a major proportion of all DENV infections. These findings are relevant for disease burden assessments, transmission modeling, and determination of vaccine impact. PMID:24127167

  6. The Role of Virus Infection in Deregulating the Cytokine Response to Secondary Bacterial Infection.

    PubMed

    Mehta, Divya; Petes, Carlene; Gee, Katrina; Basta, Sameh

    2015-12-01

    Proinflammatory cytokines are produced by macrophages and dendritic cells (DCs) after infection to stimulate T helper (Th) cells, linking innate and adaptive immunity. Virus infections can deregulate the proinflammatory cytokine response like tumor necrosis factor-α and interleukin (IL)-2, making the host more susceptible to secondary bacterial infections. Studies using various viruses such as lymphocytic choriomeningitis virus, influenza A virus, and human immunodeficiency virus have revealed several intriguing mechanisms that account for the increased susceptibility to several prevalent bacterial infections. In particular, type I interferons induced during a virus infection have been observed to play a role in suppressing the production of some key antibacterial proinflammatory cytokines such as IL-23 and IL-17. Other suppressive mechanisms as a result of cytokine deregulation by viral infections include reduced function of immune cells such as DC, macrophage, natural killer, CD4(+), and CD8(+) T cells leading to impaired clearance of secondary bacterial infections. In this study, we highlight some of the immune mechanisms that become deregulated by viral infections, and can thus become defective during secondary bacterial infections.

  7. Animal Models of Respiratory Syncytial Virus Infection and Disease

    PubMed Central

    Sacco, Randy E.; Durbin, Russell K.; Durbin, Joan E.

    2015-01-01

    The study of human respiratory syncytial virus pathogenesis and immunity has been hampered by its exquisite host specificity, and the difficulties encountered in adapting this virus to a murine host. The reasons for this obstacle are not well understood, but appear to reflect, at least in part, the inability of the virus to block the interferon response in any but the human host. This review addresses some of the issues encountered in mouse models of respiratory syncytial virus infection, and describes the advantages and disadvantages of alternative model systems. PMID:26176495

  8. Experimental Venezuelan Equine Encephalomyelitis Virus Infection of the Bovine

    PubMed Central

    Walton, Thomas E.; Johnson, Karl M.

    1972-01-01

    Two groups of four dairy cows (Bos taurus) were infected subcutaneously with the epizootic Venezuelan equine encephalomyelitis virus (VEE) strains MF-8 and San Pelayo, respectively. Animals experienced no clinical illness, but all developed significant neutropenia. Virus was recovered once each from the blood of three animals but did not exceed 102.2 SMICLD50 (Suckling mouse intracerebral lethal dose50)/ml. Specific neutralizing antibodies appeared in the serum of all animals, but there were no significant differences in titers against different naturally occurring VEE subtypes. Dairy cattle thus appear to play no role in virus transmission during VEE epizootics but may serve as retrospective immunological sentinels of virus activity. PMID:4564396

  9. Animal models of respiratory syncytial virus infection and disease.

    PubMed

    Sacco, Randy E; Durbin, Russell K; Durbin, Joan E

    2015-08-01

    The study of human respiratory syncytial virus pathogenesis and immunity has been hampered by its exquisite host specificity, and the difficulties encountered in adapting this virus to a murine host. The reasons for this obstacle are not well understood, but appear to reflect, at least in part, the inability of the virus to block the interferon response in any but the human host. This review addresses some of the issues encountered in mouse models of respiratory syncytial virus infection, and describes the advantages and disadvantages of alternative model systems.

  10. Opportunistic intruders: how viruses orchestrate ER functions to infect cells

    PubMed Central

    Cunningham, Corey Nathaniel; Tsai, Billy

    2017-01-01

    Viruses subvert the functions of their host cells to replicate and form new viral progeny. The endoplasmic reticulum (ER) has been identified as a central organelle that governs the intracellular interplay between viruses and hosts. In this Review, we analyse how viruses from vastly different families converge on this unique intracellular organelle during infection, co-opting some of the endogenous functions of the ER to promote distinct steps of the viral life cycle from entry and replication to assembly and egress. The ER can act as the common denominator during infection for diverse virus families, thereby providing a shared principle that underlies the apparent complexity of relationships between viruses and host cells. As a plethora of information illuminating the molecular and cellular basis of virus–ER interactions has become available, these insights may lead to the development of crucial therapeutic agents. PMID:27265768

  11. Inhibition of influenza A virus infection by ginsenosides

    PubMed Central

    Leon, Alberto J.; Kelvin, David J.

    2017-01-01

    Influenza viruses cause mild to severe respiratory infections in humans. Due to efficient means of transmission, the viruses infect human population on a large scale. Apart from vaccines, antiviral drugs are used to control infection; neuraminidase inhibitors are thought to be the first choice of treatment, particularly for severe cases. Rapidly evolving and emerging influenza viruses with increased frequency of viral resistance to these drugs stress the need to explore novel antiviral compounds. In this study, we investigated antiviral activity of ginseng extract and ginsenosides, the ginseng-derived triterpene and saponin compounds, against 2009 pandemic H1N1 virus in vitro and in vivo. Our data showed that treatment of mice with ginsenosides protected the animals from lethal 2009 pandemic H1N1 infection and lowered viral titers in animal lungs. Mechanistic studies revealed that ginsenosides interact with viral hemagglutinin protein and prevent the attachment of virus with α 2–3’ sialic acid receptors present on host cell surfaces. The interference in the viral attachment process subsequently minimizes viral entry into the cells and decreases the severity of the viral infection. We also describe that sugar moieties present in ginsenosides are indispensible for their attachment with viral HA protein. On the basis of our observations, we can say that ginsenosides are promising candidates for the development of antiviral drugs for influenza viruses. PMID:28187149

  12. Clinical aspects of feline immunodeficiency and feline leukemia virus infection.

    PubMed

    Hartmann, Katrin

    2011-10-15

    Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are retroviruses with a global impact on the health of domestic cats. The two viruses differ in their potential to cause disease. FIV can cause an acquired immunodeficiency syndrome that increases the risk of developing opportunistic infections, neurological diseases, and tumors. In most naturally infected cats, however, FIV itself does not cause severe clinical signs, and FIV-infected cats may live many years without any health problems. FeLV is more pathogenic, and was long considered to be responsible for more clinical syndromes than any other agent in cats. FeLV can cause tumors (mainly lymphoma), bone marrow suppression syndromes (mainly anemia) and lead to secondary infectious diseases caused by suppressive effects of the virus on bone marrow and the immune system. Today, FeLV is less important as a deadly infectious agent as in the last 20 years prevalence has been decreasing in most countries.

  13. Outbreak of West Nile Virus Infection in Greece, 2010

    PubMed Central

    Papa, Anna; Theocharopoulos, George; Dougas, Georgios; Athanasiou, Maria; Detsis, Marios; Baka, Agoritsa; Lytras, Theodoros; Mellou, Kassiani; Bonovas, Stefanos; Panagiotopoulos, Takis

    2011-01-01

    During 2010, an outbreak of West Nile virus infection occurred in Greece. A total of 197 patients with neuroinvasive disease were reported, of whom 33 (17%) died. Advanced age and a history of heart disease were independently associated with death, emphasizing the need for prevention of this infection in persons with these risk factors. PMID:22000357

  14. [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.

  15. Evidence of Apis cerana sacbrood virus infection in Apis mellifera

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sacbrood virus (SBV) is one of the most serious threats to Apis cerana but is much less destructive to Apis mellifera. In previous studies, SBV isolates infecting A. cerana and A. mellifera were identified as different serotypes, suggesting a species-barrier of SBV infection. In order to clarify whe...

  16. Leading edge analysis of transcriptomic changes during pseudorabies virus infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Eight RNA samples taken from the tracheobronchial lymph nodes (TBLN) of pigs that were either infected or non-infected with a feral isolate of porcine pseudorabies virus (PRV) were used to investigate changes in gene expression related to the pathogen. The RNA was processed into fastq files for each...

  17. ROLE OF MONOCYTES IN RESPIRATORY SYNCTIAL VIRUS (RSV) INFECTION.

    EPA Science Inventory

    ROLE OF MONOCYTES IN RESPIRATORY SYNCYTIAL VIRUS (RSV) INFECTION.
    Joleen M. Soukup and Susanne Becker, National Health and Environmental Effects Research
    Laboratory, US EPA, Research Traingle Park, NC USA.

    RSV infection in airway epithelial cells (EC) results i...

  18. ZIKA VIRUS INFECTION; VERTICAL TRANSMISSION AND FOETAL CONGENITAL ANOMALIES.

    PubMed

    Abbasi, Aziz-un-Nisa

    2016-01-01

    Zika virus (ZIKV) is an arbovirus belonging to flaviviridae family that includes Dengue, West Nile, and Yellow Fever among others. Zika virus was first discovered in 1947 in Zika forest of Uganda. It is a vector borne disease, which has been sporadically reported mostly from Africa, Pacific islands and Southeast Asia since its discovery. ZIKV infection presents as a mild illness with symptoms lasting for several days to a week after the bite of an infected mosquito. Majority of the patients have low grade fever, rash, headaches, joints pain, myalgia, and flu like symptoms. Pregnant women are more vulnerable to ZIKV infection and serious congenital anomalies can occur in foetus through trans-placental transmission. The gestation at which infection is acquired is important. Zika virus infection acquired in early pregnancy poses greater risk. There is no evidence so far about transmission through breast milk. Foetal microcephaly, Gillian Barre syndrome and other neurological and autoimmune syndromes have been reported in areas where Zika outbreaks have occurred. As infection is usually very mild no specific treatment is required. Pregnant women may be advised to take rest, get plenty of fluids. For fever and pain they can take antipyretics like paracetamol. So far no specific drugs or vaccines are available against Zika Virus Infection so prevention is the mainstay against this diseases. As ZIKV infection is a vector borne disease, prevention can be a multi-pronged strategy. These entail vector control interventions, personal protection, environmental sanitation and health education among others.

  19. Virus infections in Brazilian honey bees.

    PubMed

    Teixeira, Erica Weinstein; Chen, Yanping; Message, Dejair; Pettis, Jeff; Evans, Jay D

    2008-09-01

    This work describes the first molecular-genetic evidence for viruses in Brazilian honey bee samples. Three different bee viruses, Acute bee paralysis virus (ABPV), Black queen cell virus (BQCV), and Deformed wing virus (DWV) were identified during a screening of RNAs from 1920 individual adult bees collected in a region of southeastern Brazil that has recently shown unusual bee declines. ABPV was detected in 27.1% of colony samples, while BQCV and DWV were found in 37% and 20.3%, respectively. These levels are substantially lower than the frequencies found for these viruses in surveys from other parts of the world. We also developed and validated a multiplex RT-PCR assay for the simultaneous detection of ABPV, BQCV, and DWV in Brazil.

  20. Differential cellular gene expression in duck trachea infected with a highly or low pathogenic H5N1 avian influenza virus

    PubMed Central

    2013-01-01

    Background Avian influenza A (AI) viruses of subtypes H5 can cause serious disease outbreaks in poultry including panzootic due to H5N1 highly pathogenic (HP) viruses. These viruses are a threat not only for animal health but also public health due to their zoonotic potential. The domestic duck plays a major role in the epidemiological cycle of influenza virus subtypes H5 but little is known concerning host/pathogen interactions during influenza infection in duck species. In this study, a subtracted library from duck trachea (a primary site of influenza virus infection) was constructed to analyse and compare the host response after a highly or low pathogenic (LP) H5N1-infection. Results Here, we show that more than 200 different genes were differentially expressed in infected duck trachea to a significant degree. In addition, significant differentially expressed genes between LPAI- and HPAI-infected tracheas were observed. Gene ontology annotation was used and specific signalling pathways were identified. These pathways were different for LPAI and HPAI-infected tracheas, except for the CXCR4 signalling pathway which is implicated in immune response. A different modulation of genes in the CXCR4 signalling pathway and TRIM33 was induced in duck tracheas infected with a HPAI- or a LPAI-H5N1. Conclusion First, this study indicates that Suppressive Subtractive Hybridization (SSH) is an alternative approach to gain insights into the pathogenesis of influenza infection in ducks. Secondly, the results indicate that cellular gene expression in the duck trachea was differently modulated after infection with a LPAI-H5N1 or after infection with a HPAI-H5N1 virus. Such difference found in infected trachea, a primary infection site, could precede continuation of infection and could explain appearance of respiratory symptoms or not. PMID:24015922

  1. Viral infections of the lower respiratory tract: old viruses, new viruses, and the role of diagnosis.

    PubMed

    Pavia, Andrew T

    2011-05-01

    Viral infections of the lower respiratory tract cause an enormous disease burden in children, and the role of respiratory viruses in serious lower respiratory tract infections (LRTIs) in older adults is increasingly appreciated. Although viruses are responsible for a large proportion LRTIs, antibiotics are often prescribed. New diagnostic platforms have the potential to detect a wider range of established and newly discovered viruses with greater sensitivity. This will create additional challenges. Although it is clear that influenza, parainfluenza, respiratory syncytial virus, human metapneumovirus, and adenovirus are important causes of pneumonia, the role of rhinoviruses and some of the newly described viruses, including human coronaviruses and bocavirus, is harder to determine. Better diagnostic tests that establish the cause of LRTIs in children have the potential to both reduce overall antibiotic use and to improve the targeted use of antibiotics. In addition, rapid identification of viral infections can help control nosocomial transmission.

  2. Epstein–Barr Virus: Diseases Linked to Infection and Transformation

    PubMed Central

    Jha, Hem C.; Pei, Yonggang; Robertson, Erle S.

    2016-01-01

    Epstein–Barr virus (EBV) was first discovered in 1964, and was the first known human tumor virus now shown to be associated with a vast number of human diseases. Numerous studies have been conducted to understand infection, propagation, and transformation in various cell types linked to human diseases. However, a comprehensive lens through which virus infection, reactivation and transformation of infected host cells can be visualized is yet to be formally established and will need much further investigation. Several human cell types infected by EBV have been linked to associated diseases. However, whether these are a direct result of EBV infection or indirectly due to contributions by additional infectious agents will need to be fully investigated. Therefore, a thorough examination of infection, reactivation, and cell transformation induced by EBV will provide a more detailed view of its contributions that drive pathogenesis. This undoubtedly expand our knowledge of the biology of EBV infection and the signaling activities of targeted cellular factors dysregulated on infection. Furthermore, these insights may lead to identification of therapeutic targets and agents for clinical interventions. Here, we review the spectrum of EBV-associated diseases, the role of the encoded latent antigens, and the switch to latency or lytic replication which occurs in EBV infected cells. Furthermore, we describe the cellular processes and critical factors which contribute to cell transformation. We also describe the fate of B-cells and epithelial cells after EBV infection and the expected consequences which contribute to establishment of viral-associated pathologies. PMID:27826287

  3. Neuromuscular Manifestations of West Nile Virus Infection

    PubMed Central

    Leis, A. Arturo; Stokic, Dobrivoje S.

    2012-01-01

    The most common neuromuscular manifestation of West Nile virus (WNV) infection is a poliomyelitis syndrome with asymmetric paralysis variably involving one (monoparesis) to four limbs (quadriparesis), with or without brainstem involvement and respiratory failure. This syndrome of acute flaccid paralysis may occur without overt fever or meningoencephalitis. Although involvement of anterior horn cells in the spinal cord and motor neurons in the brainstem are the major sites of pathology responsible for neuromuscular signs, inflammation also may involve skeletal or cardiac muscle (myositis, myocarditis), motor axons (polyradiculitis), and peripheral nerves [Guillain–Barré syndrome (GBS), brachial plexopathy]. In addition, involvement of spinal sympathetic neurons and ganglia provides an explanation for autonomic instability seen in some patients. Many patients also experience prolonged subjective generalized weakness and disabling fatigue. Despite recent evidence that WNV may persist long-term in the central nervous system or periphery in animals, the evidence in humans is controversial. WNV persistence would be of great concern in immunosuppressed patients or in those with prolonged or recurrent symptoms. Support for the contention that WNV can lead to autoimmune disease arises from reports of patients presenting with various neuromuscular diseases that presumably involve autoimmune mechanisms (GBS, other demyelinating neuropathies, myasthenia gravis, brachial plexopathies, stiff-person syndrome, and delayed or recurrent symptoms). Although there is no specific treatment or vaccine currently approved in humans, and the standard remains supportive care, drugs that can alter the cascade of immunobiochemical events leading to neuronal death may be potentially useful (high-dose corticosteroids, interferon preparations, and intravenous immune globulin containing WNV-specific antibodies). Human experience with these agents seems promising based on anecdotal reports

  4. Epidemiological features and economical importance of bovine virus diarrhoea virus (BVDV) infections.

    PubMed

    Houe, H

    1999-01-01

    Infections with bovine virus diarrhoea virus (BVDV) are widespread throughout the world. Although the prevalence of infection varies among surveys, the infection tends to be endemic in many populations, reaching a maximum level of 1-2% of the cattle being persistently infected (PI) and 60-85% of the cattle being antibody positive. Persistently infected cattle are the main source for transmission of the virus. However, acutely infected cattle as well as other ruminants, either acutely or persistently infected, may transmit the virus. Transmission is most efficient by direct contact. However, as infections have been observed in closed, non-pasturing herds, other transmission routes seem likely to have some practical importance. Differences in BVDV prevalence among regions or introduction of virus in herds previously free of BVDV are often associated with particular epidemiological determinants such as cattle population density, animal trade and pasturing practices. However, on a few occasions there have been no obvious explanations for infection of individual herds. Estimates of economic losses due to BVDV infection vary depending on the immune status of the population and the pathogenicity of the infecting virus strains. Introduction of the infection into a totally susceptible population invariably causes extensive losses until a state of equilibrium is reached. Infection with highly virulent BVDV strains causing severe clinical signs and death after acute infection gives rise to substantial economical losses. At an estimated annual incidence of acute infections of 34%, the total annual losses were estimated as US$ 20 million per million calvings when modeling the losses due to a low-virulent BVDV strain. At the same incidence of infection, the losses due to a high-virulent BVDV strain were estimated as US$ 57 million per million calvings. Low-virulent BVDV infections caused maximum losses at an incidence of 45%, whereas high-virulent BVDV infections caused maximum

  5. Virus Enrichment for Single Virus Infection by Using 3D Insulator Based Dielectrophoresis

    PubMed Central

    Masuda, Taisuke; Maruyama, Hisataka; Honda, Ayae; Arai, Fumihito

    2014-01-01

    We developed an active virus filter (AVF) that enables virus enrichment for single virus infection, by using insulator-based dielectrophoresis (iDEP). A 3D-constricted flow channel design enabled the production of an iDEP force in the microfluidic chip. iDEP using a chip with multiple active virus filters (AVFs) was more accurate and faster than using a chip with a single AVF, and improved the efficiency of virus trapping. We utilized maskless photolithography to achieve the precise 3D gray-scale exposure required for fabrication of constricted flow channel. Influenza virus (A PR/8) was enriched by a negative DEP force when sinusoidal wave was applied to the electrodes within an amplitude range of 20 Vp-p and a frequency of 10 MHz. AVF-mediated virus enrichment can be repeated simply by turning the current ON or OFF. Furthermore, the negative AVF can inhibit virus adhesion onto the glass substrate. We then trapped and transported one of the enriched viruses by using optical tweezers. This microfluidic chip facilitated the effective transport of a single virus from AVFs towards the cell-containing chamber without crossing an electrode. We successfully transported the virus to the cell chamber (v = 10 µm/s) and brought it infected with a selected single H292 cell. PMID:24918921

  6. THE INFECTION OF MICE WITH SWINE INFLUENZA VIRUS

    PubMed Central

    Shope, Richard E.

    1935-01-01

    The experiments confirm the earlier observation of Andrewes, Laidlaw and Smith that the swine influenza virus is pathogenic for white mice when administered intranasally. Two field strains of the swine influenza virus were found to differ in their initial pathogenicity for mice. One strain was apparently fully pathogenic even in its 1st mouse passage while the other required 2 or 3 mouse passages to acquire full virulence for this species. Both strains, however, were initially infectious for mice, without the necessity of intervening ferret passages. There is no evidence that bacteria play any significant rôle in the mouse disease though essential in that of swine, and fatal pneumonias can be produced in mice by pure virus infections. Mice surviving the virus disease are immune to reinfection for at least a month. In mice the disease is not contagious though it is notably so in swine. The virus, while regularly producing fatal pneumonias when administered intranasally to mice, appears to be completely innocuous when given subcutaneously or intraperitoneally. Prolonged serial passage of the virus in mice does not influence its infectivity or virulence for swine or ferrets. It is a stable virus so far as its infectivity is concerned, and can be transferred at will from any one of its three known susceptible hosts to any other. In discussing these facts the stability of the swine influenza virus has been contrasted with the apparent instability of freshly isolated strains of the human influenza virus. Though the mouse is an un-natural host for the virus it is, nevertheless, useful for the study of those aspects of swine influenza which have to do with the virus only. PMID:19870434

  7. Innate immune control and regulation of influenza virus infections

    PubMed Central

    McGill, Jodi; Heusel, Jonathan W.; Legge, Kevin L.

    2009-01-01

    Adaptive immune responses are critical for the control and clearance of influenza A virus (IAV) infection. However, in recent years, it has become increasingly apparent that innate immune cells, including natural killer cells, alveolar macrophages (aMφ), and dendritic cells (DC) are essential following IAV infection in the direct control of viral replication or in the induction and regulation of virus-specific adaptive immune responses. This review will discuss the role of these innate immune cells following IAV infection, with a particular focus on DC and their ability to induce and regulate the adaptive IAV-specific immune response. PMID:19643736

  8. Fetal Magnetic Resonance Imaging Findings in Prenatal Zika Virus Infection.

    PubMed

    Sanín-Blair, José Enrique; Gutiérrez-Márquez, Carolina; Herrera, Diego A; Vossough, Arastoo

    2017-03-14

    Brain lesions and malformations have been described on ultrasonography of prenatal Zika infection; however, there are scarce reports about fetal magnetic resonance (MR) findings. We report 3 cases of fetuses with confirmed intrauterine Zika virus infection evaluated by ultrasound and fetal MR. Various morphometric measurements were assessed and brain maturation was calculated with the fetal total maturation score. Fetuses with prenatal Zika virus infection showed retardation in brain maturation indexes evaluated by fetal MR. Brain calcifications were demonstrated by neurosonography in all cases, while fetal MR characterized the specific type of cortical development malformation.

  9. Persistent infection of rabbits with bovine immunodeficiency-like virus.

    PubMed Central

    Pifat, D Y; Ennis, W H; Ward, J M; Oberste, M S; Gonda, M A

    1992-01-01

    Chronic infection of rabbits was induced by a single intraperitoneal injection of bovine immunodeficiency-like virus (BIV)-infected cells. Ten BIV-infected animals were monitored serologically for up to 2 years. Results of serologic and virus rescue assays indicated that all animals became infected and demonstrated a rapid and sustained BIV-specific humoral response. BIV was rescued by cocultivation from spleen, lymph nodes, and peripheral blood leukocytes of infected animals. Viral DNA in immune tissues was confirmed by polymerase chain reaction amplification of BIV sequences. These data and specific immunohistochemical staining of mononuclear cells of the spleen for BIV antigen suggest that the infection is targeted to immune system cells. Images PMID:1318416

  10. Immune Modulation in Primary Vaccinia virus Zoonotic Human Infections

    PubMed Central

    Gomes, Juliana Assis Silva; de Araújo, Fernanda Fortes; Trindade, Giliane de Souza; Quinan, Bárbara Resende; Drumond, Betânia Paiva; Ferreira, Jaqueline Maria Siqueira; Mota, Bruno Eduardo Fernandes; Nogueira, Maurício Lacerda; Kroon, Erna Geessien; Abrahão, Jônatas Santos; Côrrea-Oliveira, Rodrigo; da Fonseca, Flávio Guimarães

    2012-01-01

    In 2010, the WHO celebrated the 30th anniversary of the smallpox eradication. Ironically, infections caused by viruses related to smallpox are being increasingly reported worldwide, including Monkeypox, Cowpox, and Vaccinia virus (VACV). Little is known about the human immunological responses elicited during acute infections caused by orthopoxviruses. We have followed VACV zoonotic outbreaks taking place in Brazil and analyzed cellular immune responses in patients acutely infected by VACV. Results indicated that these patients show a biased immune modulation when compared to noninfected controls. Amounts of B cells are low and less activated in infected patients. Although present, T CD4+ cells are also less activated when compared to noninfected individuals, and so are monocytes/macrophages. Similar results were obtained when Balb/C mice were experimentally infected with a VACV sample isolated during the zoonotic outbreaks. Taking together, the data suggest that zoonotic VACVs modulate specific immune cell compartments during an acute infection in humans. PMID:22229039

  11. Autophagy Stimulation Abrogates Herpes simplex Virus-1 Infection

    PubMed Central

    Yakoub, Abraam M.; Shukla, Deepak

    2015-01-01

    Herpes simplex virus-1 (HSV-1) is a double-stranded DNA virus that causes life-long infections. HSV-1 infections may lead to herpetic stromal keratitis that may advance to corneal blindness. HSV-1 infections can also cause fatal conditions, such as herpes encephalitis, or neonatal disease. A major virulence mechanism of HSV-1 is the control of autophagy, an innate immune defense strategy that could otherwise degrade viral particles. Here, to investigate a new mechanism for antiviral therapy, we tested the effect of various autophagy inducers (physiological and pharmacological) on infection. Autophagy stimulation was confirmed to significantly suppress HSV-1 infection in various cell types, without affecting cell viability. This study establishes the importance of autophagy for regulating HSV-1 infection, and provides a proof-of-principle evidence for a novel antiviral mechanism. PMID:25856282

  12. Immune inhibition of virus release from herpes simplex virus-infected cells by human sera.

    PubMed

    Shariff, D M; Hallworth, J; Desperbasques, M; Buchan, A; Skinner, G R

    1988-01-01

    Human sera contain antibody (IVR antibody) which will inhibit the release of herpes simplex virus type 1 from virus-infected cells. This antibody activity was removed by adsorption of sera with virus-infected cell extract. There was a positive correlation between IVR and neutralizing antibody activity, particularly when measured by augmented neutralization test; measurement of IVR antibody was equally as sensitive as measurement of neutralizing antibody by augmented neutralization test. IVR antibody levels provided indication of a history of recurrent herpes labialis, the pattern of antibody response following primary herpetic infection, and indication of response to Skinner herpes vaccine in human subjects. It is suggested that consideration should be given to measurement of IVR antibody in both clinical and epidemiological studies of herpes and other virus infections.

  13. Basal Autophagy Is Required for Herpes simplex Virus-2 Infection

    PubMed Central

    Yakoub, Abraam M.; Shukla, Deepak

    2015-01-01

    Autophagy is a conserved catabolic process of the cell, which plays an important role in regulating plethora of infections. The role of autophagy in Herpes simplex virus-2 (HSV-2) infection is unknown. Here, we found that HSV-2 does not allow induction of an autophagic response to infection, but maintains basal autophagy levels mostly unchanged during productive infection. Thus, we investigated the importance of basal autophagy for HSV-2 infection, using pharmacological autophagy suppression or cells genetically deficient in an autophagy-essential gene (ATG5). Interference with basal autophagy flux in cells significantly reduced viral replication and diminished the infection. These results indicate that basal autophagy plays an indispensable role required for a productive infection. Importantly, this study draws a sharp distinction between induced and basal autophagy, where the former acts as a viral clearance mechanism abrogating infection, while the latter supports infection. PMID:26248741

  14. Interferon Response in Hepatitis C Virus (HCV) Infection: Lessons from Cell Culture Systems of HCV Infection.

    PubMed

    Sung, Pil Soo; Shin, Eui-Cheol; Yoon, Seung Kew

    2015-10-07

    Hepatitis C virus (HCV) is a positive-stranded RNA virus that infects approximately 130-170 million people worldwide. In 2005, the first HCV infection system in cell culture was established using clone JFH-1, which was isolated from a Japanese patient with fulminant HCV infection. JFH-1 replicates efficiently in hepatoma cells and infectious virion particles are released into the culture supernatant. The development of cell culture-derived HCV (HCVcc) systems has allowed us to understand how hosts respond to HCV infection and how HCV evades host responses. Although the mechanisms underlying the different outcomes of HCV infection are not fully understood, innate immune responses seem to have a critical impact on the outcome of HCV infection, as demonstrated by the prognostic value of IFN-λ gene polymorphisms among patients with chronic HCV infection. Herein, we review recent research on interferon response in HCV infection, particularly studies using HCVcc infection systems.

  15. Multiple Epstein-Barr virus infections in healthy individuals

    NASA Technical Reports Server (NTRS)

    Walling, Dennis M.; Brown, Abigail L.; Etienne, Wiguins; Keitel, Wendy A.; Ling, Paul D.; Butel, J. S. (Principal Investigator)

    2003-01-01

    We employed a newly developed genotyping technique with direct representational detection of LMP-1 gene sequences to study the molecular epidemiology of Epstein-Barr virus (EBV) infection in healthy individuals. Infections with up to five different EBV genotypes were found in two of nine individuals studied. These results support the hypothesis that multiple EBV infections of healthy individuals are common. The implications for the development of an EBV vaccine are discussed.

  16. West Nile virus infection decreases fecundity of Culex tarsalis females.

    PubMed

    Styer, Linda M; Meola, Mark A; Kramer, Laura D

    2007-11-01

    West Nile virus (family Flaviviridae, genus Flavivirus, WNV) persistently infects many mosquito tissues, and it has been associated with cytopathological changes in midgut muscles and salivary glands. However, the effects of WNV infection on mosquito fitness (survival and reproduction) are not known. We conducted a life table study of individually housed female Culex tarsalis Coquillett. After an initial bloodmeal from a WNV-infected or uninfected chicken, mosquitoes were provided sucrose and offered weekly opportunities to feed on a hanging blood drop. WNV transmission status was determined by testing the remaining blood drop for virus after mosquito feeding. Dead mosquitoes and eggs were collected daily. Mosquito legs and bodies were tested for WNV, and eggs were counted and allowed to hatch. Two replicates of this experiment were performed, with a total of 62 mosquitoes that fed on a WNV-infected chicken (of which 21 became infected) and 43 mosquitoes that fed on an uninfected chicken. Fecundity of WNV-infected mosquitoes was significantly lower than that of uninfected mosquitoes, especially during the first oviposition. WNV infection was associated with smaller egg rafts, whereas increasing wing length and WNV titer in the legs had a positive effect on egg raft size. Additionally, infected mosquitoes had lower egg hatch rates than did uninfected mosquitoes. There were no significant differences in survival between infected and uninfected mosquitoes. Blood feeding rates were higher in infected mosquitoes than in uninfected mosquitoes. A small amount of virus (average, 378; range, 5-5000 plaque-forming units) was transmitted to the blood drops fed upon by infected mosquitoes. Although WNV infection negatively impacts mosquito reproduction, facets of mosquito biology that are critical to virus transmission success were either not affected (survival) or changed in such a way as to result in enhanced vectorial capacity (blood feeding).

  17. Molecular mimicry in virus infection: crossreaction of measles virus phosphoprotein or of herpes simplex virus protein with human intermediate filaments.

    PubMed Central

    Fujinami, R S; Oldstone, M B; Wroblewska, Z; Frankel, M E; Koprowski, H

    1983-01-01

    Using monoclonal antibodies, we demonstrate that the phosphoprotein of measles virus and a protein of herpes simplex virus type 1 crossreact with an intermediate filament protein of human cells. This intermediate filament protein, probably vimentin, has a molecular weight of 52,000, whereas the molecular weights of the measles viral phosphoprotein and the herpes virus protein are 70,000 and 146,000, respectively. Crossreactivity was shown by immunofluorescent staining of infected and uninfected cells and by immunoblotting. The monoclonal antibody against measles virus phosphoprotein did not react with herpes simplex virus protein and vice versa, indicating that these monoclonal antibodies recognize different antigenic determinants on the intermediate filament molecule. The significance of these results in explaining the appearance of autoantibodies during virus infections in humans is discussed. Images PMID:6300911

  18. Three-Dimensional Engineered High Fidelity Normal Human Lung Tissue-Like Assemblies (TLA) as Targets for Human Respiratory Virus Infections

    NASA Technical Reports Server (NTRS)

    Goodwin, T. J.; Deatly, A. M.; Suderman, M. T.; Lin, Y.-H.; Chen, W.; Gupta, C. K.; Randolph, V. B.; Udem, S. A.

    2003-01-01

    Unlike traditional two-dimensional (2D) cell cultures, three-dimensional (3D) tissue-like assemblies (TLA) (Goodwin et aI, 1992, 1993, 2000 and Nickerson et aI. , 2001,2002) offer high organ fidelity with the potential to emulate the infective dynamics of viruses and bacteria in vivo. Thus, utilizing NASA micro gravity Rotating Wall Vessel (RWV) technology, in vitro human broncho-epithelial (HBE) TLAs were engineered to mimic in vivo tissue for study of human respiratory viruses. These 3D HBE TLAs were propagated from a human broncho-tracheal cell line with a mesenchymal component (HBTC) as the foundation matrix and either an adult human broncho-epithelial cell (BEAS-2B) or human neonatal epithelial cell (16HBE140-) as the overlying element. Resulting TLAs share several characteristic features with in vivo human respiratory epithelium including tight junctions, desmosomes and cilia (SEM, TEM). The presence of epithelium and specific lung epithelium markers furthers the contention that these HBE cells differentiate into TLAs paralleling in vivo tissues. A time course of infection of these 3D HBE TLAs with human respiratory syncytial virus (hRSV) wild type A2 strain, indicates that virus replication and virus budding are supported and manifested by increasing virus titer and detection of membrane-bound F and G glycoproteins. Infected 3D HBE TLAs remain intact for up to 12 days compared to infected 2D cultures that are destroyed in 2-3 days. Infected cells show an increased vacuolation and cellular destruction (by transmission electron microscopy) by day 9; whereas, uninfected cells remain robust and morphologically intact. Therefore, the 3D HBE TLAs mimic aspects of human respiratory epithelium providing a unique opportunity to analyze, for the first time, simulated in vivo viral infection independent of host immune response.

  19. Characterisation of three novel giant viruses reveals huge diversity among viruses infecting Prymnesiales (Haptophyta).

    PubMed

    Johannessen, Torill Vik; Bratbak, Gunnar; Larsen, Aud; Ogata, Hiroyuki; Egge, Elianne S; Edvardsen, Bente; Eikrem, Wenche; Sandaa, Ruth-Anne

    2015-02-01

    We have isolated three novel lytic dsDNA-viruses from Raunefjorden (Norway) that are putative members of the Mimiviridae family, namely Haptolina ericina virus RF02 (HeV RF02), Prymnesium kappa virus RF01 (PkV RF01), and Prymnesium kappa virus RF02 (PkV RF02). Each of the novel haptophyte viruses challenges the common conceptions of algal viruses with respect to host range, phylogenetic affiliation and size. PkV RF01 has a capsid of ~310 nm and is the largest algal virus particle ever reported while PkV RF01 and HeV RF02 were able to infect different species, even belonging to different genera. Moreover, PkV RF01 and HeV RF02 infected the same hosts, but phylogenetic analysis placed them in different groups. Our results reveal large variation among viruses infecting closely related microalgae, and challenge the common conception that algal viruses have narrow host range, and phylogeny reflecting their host affiliation.

  20. Why Zika virus infection has become a public health concern?

    PubMed

    Chen, Hui-Lan; Tang, Ren-Bin

    2016-04-01

    Prior to 2015, Zika Virus (ZIKV) outbreaks had occurred in areas of Africa, Southeast Asia, and the Pacific Islands. Although a causal relationship between Zika infection during pregnancy and microcephaly is strongly suspected, such a connection has not yet been scientifically proven. In May 2015, the outbreak of ZIKV infection in Brazil led to reports of syndrome and pregnant women giving birth to babies with birth defects and poor pregnancy outcomes; the Pan American Health Organization (PAHO) issued an alert regarding the first confirmed ZIKV infection in Brazil. Currently, ZIKV outbreaks are ongoing and it will be difficult to predict how the virus will spread over time. ZIKV is transmitted to humans primarily through the bite of infected mosquitos, Aedes aegypti and Aedes albopictus. These mosquitoes are the principle vectors of dengue, and ZIKV disease generally is reported to include symptoms associated with acute febrile illnesses that clinically resembles dengue fever. The laboratory diagnosis can be performed by using reverse-transcriptase polymerase chain reaction (RT-PCR) on serum, viral nucleic acid and virus-specific immunoglobulin M. There is currently no vaccine and antiviral treatment available for ZIKV infection, and the only way to prevent congenital ZIKV infection is to prevent maternal infection. In February 2016, the Taiwan Centers for Disease Control (Taiwan CDC) activated ZIKV as a Category V Notifiable Infectious Disease similar to Ebola virus disease and MERS.

  1. Diversity of Viruses Infecting the Green Microalga Ostreococcus lucimarinus

    PubMed Central

    Derelle, Evelyne; Monier, Adam; Cooke, Richard; Worden, Alexandra Z.

    2015-01-01

    ABSTRACT The functional diversity of eukaryotic viruses infecting a single host strain from seawater samples originating from distant marine locations is unknown. To estimate this diversity, we used lysis plaque assays to detect viruses that infect the widespread species Ostreococcus lucimarinus, which is found in coastal and mesotrophic systems, and O. tauri, which was isolated from coastal and lagoon sites from the northwest Mediterranean Sea. Detection of viral lytic activities against O. tauri was not observed using seawater from most sites, except those close to the area where the host strain was isolated. In contrast, the more cosmopolitan O. lucimarinus species recovered viruses from locations in the Atlantic and Pacific Oceans and the Mediterranean Sea. Six new O. lucimarinus viruses (OlVs) then were characterized and their genomes sequenced. Two subgroups of OlVs were distinguished based on their genetic distances and on the inversion of a central 32-kb-long DNA fragment, but overall their genomes displayed a high level of synteny. The two groups did not correspond to proximity of isolation sites, and the phylogenetic distance between these subgroups was higher than the distances observed among viruses infecting O. tauri. Our study demonstrates that viruses originating from very distant sites are able to infect the same algal host strain and can be more diverse than those infecting different species of the same genus. Finally, distinctive features and evolutionary distances between these different viral subgroups does not appear to be linked to biogeography of the viral isolates. IMPORTANCE Marine eukaryotic phytoplankton virus diversity has yet to be addressed, and more specifically, it is unclear whether diversity is connected to geographical distance and whether differential infection and lysis patterns exist among such viruses that infect the same host strain. Here, we assessed the genetic distance of geographically segregated viruses that infect the

  2. Antiviral activity of lanatoside C against dengue virus infection.

    PubMed

    Cheung, Yan Yi; Chen, Karen Caiyun; Chen, Huixin; Seng, Eng Khuan; Chu, Justin Jang Hann

    2014-11-01

    Dengue infection poses a serious threat globally due to its recent rapid spread and rise in incidence. Currently, there is no approved vaccine or effective antiviral drug for dengue virus infection. In response to the urgent need for the development of an effective antiviral for dengue virus, the US Drug Collection library was screened in this study to identify compounds with anti-dengue activities. Lanatoside C, an FDA approved cardiac glycoside was identified as a candidate anti-dengue compound. Our data revealed that lanatoside C has an IC50 of 0.19μM for dengue virus infection in HuH-7 cells. Dose-dependent reduction in dengue viral RNA and viral proteins synthesis were also observed upon treatment with increasing concentrations of lanatoside C. Time of addition study indicated that lanatoside C inhibits the early processes of the dengue virus replication cycle. Furthermore, lanatoside C can effectively inhibit all four serotypes of dengue virus, flavivirus Kunjin, alphavirus Chikungunya and Sindbis virus as well as the human enterovirus 71. These findings suggest that lanatoside C possesses broad spectrum antiviral activity against several groups of positive-sense RNA viruses.

  3. Quantification of airborne African swine fever virus after experimental infection.

    PubMed

    de Carvalho Ferreira, H C; Weesendorp, E; Quak, S; Stegeman, J A; Loeffen, W L A

    2013-08-30

    Knowledge on African Swine Fever (ASF) transmission routes can be useful when designing control measures against the spread of ASF virus (ASFV). Few studies have focused on the airborne transmission route, and until now no data has been available on quantities of ASF virus (ASFV) in the air. Our aim was to validate an air sampling technique for ASF virus (ASFV) that could be used to detect and quantify virus excreted in the air after experimental infection of pigs. In an animal experiment with the Brazil'78, the Malta'78 and Netherlands'86 isolates, air samples were collected at several time points. For validation of the air sampling technique, ASFV was aerosolised in an isolator, and air samples were obtained using the MD8 air scan device, which was shown to be suitable to detect ASFV. The half-life of ASFV in the air was on average 19 min when analysed by PCR, and on average 14 min when analysed by virus titration. In rooms with infected pigs, viral DNA with titres up to 10(3.2) median tissue culture infective dose equivalents (TCID50eq.)/m(3) could be detected in air samples from day 4 post-inoculation (dpi 4) until the end of the experiments, at dpi 70. In conclusion, this study shows that pigs infected with ASFV will excrete virus in the air, particularly during acute disease. This study provides the first available parameters to model airborne transmission of ASFV.

  4. Infection of Dendritic Cells by Lymphocytic Choriomeningitis Virus

    PubMed Central

    Sevilla, N.; Kunz, S.; McGavern, D.

    2017-01-01

    Dendritic cells (DCs) comprise the major antigen-presenting cells (APCs) of the host, uniquely programmed to stimulate immunologically naïve T lymphocytes. Viruses that can target and disorder the function of these cells enjoy a selective advantage. The cellular receptor for lymphocytic choriomeningitis virus (LCMV), Lassa fever virus (LFV), and several other arenaviruses is α-dystroglycan (α-DG). Among cells of the immune system, CD11c+ and DEC-205+ DCs primarily and preferentially express α-DG. By selection, strains and variants of LCMV generated as quasi-species that bind α-DG with high affinity replicate in the majority of CD11c+ and DEC-205+ (>75%) DCs, causing a generalized immunosuppression, and establish a persistent infection. In contrast, viral strains and variants that bind with low affinity to α-DG display minimal replication in CD11c+ and DEC-205+ DCs (<10%), rarely replicate in the white pulp, and generate a robust anti-LCMV CTL response that clears the virus infection. Hence, receptor-virus interaction on DCs in vivo is an essential step in the initiation of virus-induced immunosuppression and viral persistence. Investigation into the mechanism of how virus-infected DCs cause immunosuppression reveals loss of MHC class II surface expression and costimulatory molecules on surface of such DCs. As a consequence DCs are unable to act as APCs, initiate immune responses, and have a defect in migration into the T cell area. These data indicate that LCMV infection influences DC maturation and migration, leading to decreased T cell stimulatory capacity of DCs, events essential for the initiation of immune responses. Because several other viruses known to cause immunosuppression (HIV, measles) interact with DCs, the observations noted here are likely a common selective mechanism by which viruses also are able to evade the host s immune system. PMID:12797446

  5. Infection of cells by Sindbis virus at low temperature

    SciTech Connect

    Wang Gongbo; Hernandez, Raquel; Weninger, Keith; Brown, Dennis T. . E-mail: dennis_brown@ncsu.edu

    2007-06-05

    Sindbis virus, which belongs to the family Togaviridae genus Alphavirus infects a variety of vertebrate and invertebrate cells. The initial steps of Sindbis virus infection involve attachment, penetration and uncoating. Two different pathways of infection have been proposed for Alphaviruses. One proposed mechanism involves receptor mediated virion endocytosis followed by membrane fusion triggered by endosome acidification. This virus-host membrane fusion model, well established by influenza virus, has been applied to other unrelated membrane-containing viruses including Alphaviruses. The other mechanism proposes direct penetration of the cell plasma membrane by the virus glycoproteins in the absence of membrane fusion. This alternate model is supported by both ultrastructural [Paredes, A.M., Ferreira, D., Horton, M., Saad, A., Tsuruta, H., Johnston, R., Klimstra, W., Ryman, K., Hernandez, R., Chiu, W., Brown, D.T., 2004. Conformational changes in Sindbis virions resulting from exposure to low pH and interactions with cells suggest that cell penetration may occur at the cell surface in the absence of membrane fusion. Virology 324(2), 373-386] and biochemical [Koschinski, A., Wengler, G., Wengler, G., and Repp, H., 2005. Rare earth ions block the ion pores generated by the class II fusion proteins of alphaviruses and allow analysis of the biological functions of these pores. J. Gen. Virol. 86(Pt. 12), 3311-3320] studies. We have examined the ability of Sindbis virus to infect Baby Hamster Kidney (BHK) cells at temperatures which block endocytosis. We have found that under these conditions Sindbis virus infects cells in a temperature- and time-dependent fashion.

  6. [Economic consequences of an infection with the bovine diarrhea virus (BVD virus) in 15 dairy farms].

    PubMed

    Wentink, G H; Dijkhuizen, A A

    1990-11-15

    In outbreaks of disease with the bovine virus diarrhoea virus (BVD virus), the economic loss to fourteen dairy farms was determined on the basis of the amount of loss per dairy cow. The patients included cases of abortion, stillbirths, delivery of calves showing lesions, lesions of the feet, mucosal disease and animals persistently infected with BVD virus. BVD virus was isolated from several cases of disease on all farms. It was not possible, however, directly to examine all individuals for the presence of the virus. The amount of loss caused by BVD virus was Dfl. 136,- per average dairy cow. The amount varied between individual farms from Dfl. 42,- to Dfl. 285,- per dairy cow.

  7. Deep Sequencing Analysis of Apple Infecting Viruses in Korea

    PubMed Central

    Cho, In-Sook; Igori, Davaajargal; Lim, Seungmo; Choi, Gug-Seoun; Hammond, John; Lim, Hyoun-Sub; Moon, Jae Sun

    2016-01-01

    Deep sequencing has generated 52 contigs derived from five viruses; Apple chlorotic leaf spot virus (ACLSV), Apple stem grooving virus (ASGV), Apple stem pitting virus (ASPV), Apple green crinkle associated virus (AGCaV), and Apricot latent virus (ApLV) were identified from eight apple samples showing small leaves and/or growth retardation. Nucleotide (nt) sequence identity of the assembled contigs was from 68% to 99% compared to the reference sequences of the five respective viral genomes. Sequences of ASPV and ASGV were the most abundantly represented by the 52 contigs assembled. The presence of the five viruses in the samples was confirmed by RT-PCR using specific primers based on the sequences of each assembled contig. All five viruses were detected in three of the samples, whereas all samples had mixed infections with at least two viruses. The most frequently detected virus was ASPV, followed by ASGV, ApLV, ACLSV, and AGCaV which were withal found in mixed infections in the tested samples. AGCaV was identified in assembled contigs ID 1012480 and 93549, which showed 82% and 78% nt sequence identity with ORF1 of AGCaV isolate Aurora-1. ApLV was identified in three assembled contigs, ID 65587, 1802365, and 116777, which showed 77%, 78%, and 76% nt sequence identity respectively with ORF1 of ApLV isolate LA2. Deep sequencing assay was shown to be a valuable and powerful tool for detection and identification of known and unknown virome in infected apple trees, here identifying ApLV and AGCaV in commercial orchards in Korea for the first time. PMID:27721694

  8. Deep Sequencing Analysis of Apple Infecting Viruses in Korea.

    PubMed

    Cho, In-Sook; Igori, Davaajargal; Lim, Seungmo; Choi, Gug-Seoun; Hammond, John; Lim, Hyoun-Sub; Moon, Jae Sun

    2016-10-01

    Deep sequencing has generated 52 contigs derived from five viruses; Apple chlorotic leaf spot virus (ACLSV), Apple stem grooving virus (ASGV), Apple stem pitting virus (ASPV), Apple green crinkle associated virus (AGCaV), and Apricot latent virus (ApLV) were identified from eight apple samples showing small leaves and/or growth retardation. Nucleotide (nt) sequence identity of the assembled contigs was from 68% to 99% compared to the reference sequences of the five respective viral genomes. Sequences of ASPV and ASGV were the most abundantly represented by the 52 contigs assembled. The presence of the five viruses in the samples was confirmed by RT-PCR using specific primers based on the sequences of each assembled contig. All five viruses were detected in three of the samples, whereas all samples had mixed infections with at least two viruses. The most frequently detected virus was ASPV, followed by ASGV, ApLV, ACLSV, and AGCaV which were withal found in mixed infections in the tested samples. AGCaV was identified in assembled contigs ID 1012480 and 93549, which showed 82% and 78% nt sequence identity with ORF1 of AGCaV isolate Aurora-1. ApLV was identified in three assembled contigs, ID 65587, 1802365, and 116777, which showed 77%, 78%, and 76% nt sequence identity respectively with ORF1 of ApLV isolate LA2. Deep sequencing assay was shown to be a valuable and powerful tool for detection and identification of known and unknown virome in infected apple trees, here identifying ApLV and AGCaV in commercial orchards in Korea for the first time.

  9. Respiratory virus infections among children in South China.

    PubMed

    Cai, Xiao-Ying; Wang, Qiong; Lin, Guang-Yu; Cai, Zhi-Wei; Lin, Chuang-Xing; Chen, Pai-Zhen; Zhou, Xiao-Hua; Xie, Jin-Chun; Lu, Xue-Dong

    2014-07-01

    Acute respiratory tract infection is an important cause of morbidity and mortality with a worldwide disease burden. This study aimed to determine the prevalence and clinical characteristics of children with viral-induced acute respiratory tract infection, in Southern China. Nasopharyngeal aspirate samples from 1,980 pediatric patients with suspected acute respiratory tract infection, and 82 samples from healthy subject controls were collected for routine examination at the Second Affiliated Hospital of Shantou University Medical College, from October 2007 to August 2011. Specimens were tested by multiplex polymerase chain reaction (mPCR). At least one or more viruses were detected from 1,087 samples (54.9%). These included laboratory confirmations for 446 respiratory syncytial virus (RSV), 386 influenza virus A (FluA), 315 human rhinovirus (HRV), 135 human bocavirus (HBoV), 119 Parainfluenza virus 3 (PIV3), 82 Parainfluenza virus 1 (PIV1), 66 adenovirus (ADV), 53 WU polyomavirus (WUPyV), 52 human metapneumovirus (hMPV), and 29 influenza virus B (FluB) samples. Samples from healthy subjects were negative for any virus. Of the patients with positive specimens, 107 (9.8%) were admitted to pediatric intensive care unit (PICU). Co-infection with at least two of the viral pathogens under study was observed in 325 of the 1,980 patients (16.4% of the total number of cases). These findings may help in the diagnosis of viral infections of the respiratory tract in children, and help to consider current and potential therapeutic approaches for the treatment of acute respiratory tract infection, and further respiratory complications.

  10. Occult hepatitis B virus and hepatitis C virus infections.

    PubMed

    Carreño, Vicente; Bartolomé, Javier; Castillo, Inmaculada; Quiroga, Juan Antonio

    2008-01-01

    Occult HBV infection is a well-recognised clinical entity characterised by the detection of HBV-DNA in serum and/or in liver in the absence of detectable hepatitis B surface antigen (HBsAg). Occult HBV infection has been described not only in patients who have resolved an acute or chronic HBV infection but also in patients without any serological markers of a past HBV infection. Occult HBV infection in patients with chronic HCV infection may induce more severe liver disease and lower response rate to interferon treatment. The existence of occult HCV infections has been also reported more recently. Occult HCV infection is characterised by the presence of HCV-RNA in liver and peripheral blood mononuclear cells in the absence of detectable serum HCV-RNA. Occult HCV infection may occur under two different clinical situations: in hepatitis C antibody-(anti-HCV) negative and serum HCV-RNA-negative patients with abnormal liver function tests and in anti-HCV-positive patients who have no detectable serum HCV-RNA and who have normal liver enzymes. The clinical relevance of occult HCV infections is still under investigation.

  11. Pathogenesis of Lassa fever virus infection: I. Susceptibility of mice to recombinant Lassa Gp/LCMV chimeric virus.

    PubMed

    Lee, Andrew M; Cruite, Justin; Welch, Megan J; Sullivan, Brian; Oldstone, Michael B A

    2013-08-01

    Lassa virus (LASV) is a BSL-4 restricted agent. To allow study of infection by LASV under BSL-2 conditions, we generated a recombinant virus in which the LASV glycoprotein (Gp) was placed on the backbone of lymphocytic choriomeningitis virus (LCMV) Cl13 nucleoprotein, Z and polymerase genes (rLCMV Cl13/LASV Gp). The recombinant virus displayed high tropism for dendritic cells following in vitro or in vivo infection. Inoculation of immunocompetent adults resulted in an acute infection, generation of virus-specific CD8(+) T cells and clearance of the infection. Inoculation of newborn mice with rLCMV Cl13/LASV Gp resulted in a life-long persistent infection. Interestingly, adoptive transfer of rLCMV Cl13/LASV Gp immune memory cells into such persistently infected mice failed to purge virus but, in contrast, cleared virus from mice persistently infected with wt LCMV Cl13.

  12. Does a feline leukemia virus infection pave the way for Bartonella henselae infection in cats?

    PubMed

    Buchmann, Alexandra U; Kershaw, Olivia; Kempf, Volkhard A J; Gruber, Achim D

    2010-09-01

    Domestic cats serve as the reservoir hosts of Bartonella henselae and may develop mild clinical symptoms or none after experimental infection. In humans, B. henselae infection can result in self-limiting cat scratch disease. However, immunocompromised patients may suffer from more-severe courses of infection or may even develop the potentially lethal disease bacillary angiomatosis. It was reasoned that cats with immunocompromising viral infections may react similarly to B. henselae infection. The aim of our study was to investigate the influence of the most important viruses known to cause immunosuppression in cats-Feline leukemia virus (FeLV), Feline immunodeficiency virus (FIV), and Feline panleukopenia virus (FPV)-on natural B. henselae infection in cats. Accordingly, 142 cats from animal shelters were necropsied and tested for B. henselae and concurrent infections with FeLV, FIV, or FPV by PCR and immunohistochemistry. A significant association was found between B. henselae and FeLV infections (P = 0.00028), but not between B. henselae and FIV (P = 1.0) or FPV (P = 0.756) infection, age (P = 0.392), or gender (P = 0.126). The results suggest that susceptibility to B. henselae infection is higher in cats with concurrent FeLV infections, regardless of whether the infection is latent or progressive. Histopathology and immunohistochemistry for B. henselae failed to identify lesions that could be attributed specifically to B. henselae infection. We conclude that the course of natural B. henselae infection in cats does not seem to be influenced by immunosuppressive viral infections in general but that latent FeLV infection may predispose cats to B. henselae infection or persistence.

  13. Suppression of influenza virus infection by the orf virus isolated in Taiwan

    PubMed Central

    LIN, Fong-Yuan; TSENG, Yeu-Yang; CHAN, Kun-Wei; KUO, Shu-Ting; YANG, Cheng-Hsiung; WANG, Chi-Young; TAKASU, Masaki; HSU, Wei-Li; WONG, Min-Liang

    2015-01-01

    Orf virus (ORFV), a member of parapoxvirus, is an enveloped virus with genome of double-stranded DNA. ORFV causes contagious pustular dermatitis or contagious ecthyma in sheep and goats worldwide. In general, detection of viral DNA and observing ORFV virion in tissues of afflicted animals are two methods commonly used for diagnosis of orf infection; however, isolation of the ORFV in cell culture using virus-containing tissue as inoculum is known to be difficult. In this work, the ORFV (Hoping strain) isolated in central Taiwan was successfully grown in cell culture. We further examined the biochemical characteristic of our isolate, including viral genotyping, viral mRNA and protein expression. By electron microscopy, one unique form of viral particle from ORFV infected cellular lysate was demonstrated in the negative-stained field. Moreover, immunomodulating and anti-influenza virus properties of this ORFV were investigated. ORFV stimulated human monocytes (THP-1) secreting proinflammatory cytokines IL-8 and TNF-α. And, pre-treatment of ORFV-infected cell medium prevents A549 cells from subsequent type A influenza virus (IAV) infection. Similarly, mice infected with ORFV via both intramuscular and subcutaneous routes at two days prior to IAV infection significantly decreased the replication of IAV. In summary, the results of a current study indicated our Hoping strain harbors the immune modulator property; with such a bio-adjuvanticity, we further proved that pre-exposure of ORFV protects animals from subsequent IAV infection. PMID:25855509

  14. Occult hepatitis B virus infection among Mexican human immunodeficiency virus-1-infected patients

    PubMed Central

    Alvarez-Muñoz, Ma Teresa; Maldonado-Rodriguez, Angelica; Rojas-Montes, Othon; Torres-Ibarra, Rocio; Gutierrez-Escolano, Fernanda; Vazquez-Rosales, Guillermo; Gomez, Alejandro; Muñoz, Onofre; Torres, Javier; Lira, Rosalia

    2014-01-01

    AIM: To determine the frequency of occult hepatitis B infection (OHBI) in a group of human immunodeficiency virus (HIV)-1+/ hepatitis B surface antigen negative (HBsAg)- patients from Mexico. METHODS: We investigated the presence of OHBI in 49 HIV-1+/HBsAg- patients. Hepatitis B virus (HBV) DNA was analyzed using nested PCR to amplify the Core (C) region and by real-time PCR to amplify a region of the S and X genes. The possible associations between the variables and OHBI were investigated using Pearson’s χ2 and/or Fisher’s exact test. RESULTS: We found that the frequency of OHBI was 49% among the group of 49 HIV-1+/HBsAg- patients studied. The presence of OHBI was significantly associated with the HIV-1 RNA viral load [odds ratio (OR) = 8.75; P = 0.001; 95%CI: 2.26-33.79] and with HIV-antiretroviral treatment with drugs that interfere with HBV replication (lamivudine, tenofovir or emtricitabine) (OR = 0.25; P = 0.05; 95%CI: 0.08-1.05). CONCLUSION: The OHBI frequency is high among 49 Mexican HIV-1+/HBsAg- patients and it was more frequent in patients with detectable HIV RNA, and less frequent in patients who are undergoing HIV-ARV treatment with drugs active against HBV. PMID:25309083

  15. Deep sequencing in the management of hepatitis virus infections.

    PubMed

    Quer, Josep; Rodríguez-Frias, Francisco; Gregori, Josep; Tabernero, David; Soria, Maria Eugenia; García-Cehic, Damir; Homs, Maria; Bosch, Albert; Pintó, Rosa María; Esteban, Juan Ignacio; Domingo, Esteban; Perales, Celia

    2016-12-28

    The hepatitis viruses represent a major public health problem worldwide. Procedures for characterization of the genomic composition of their populations, accurate diagnosis, identification of multiple infections, and information on inhibitor-escape mutants for treatment decisions are needed. Deep sequencing methodologies are extremely useful for these viruses since they replicate as complex and dynamic quasispecies swarms whose complexity and mutant composition are biologically relevant traits. Population complexity is a major challenge for disease prevention and control, but also an opportunity to distinguish among related but phenotypically distinct variants that might anticipate disease progression and treatment outcome. Detailed characterization of mutant spectra should permit choosing better treatment options, given the increasing number of new antiviral inhibitors available. In the present review we briefly summarize our experience on the use of deep sequencing for the management of hepatitis virus infections, particularly for hepatitis B and C viruses, and outline some possible new applications of deep sequencing for these important human pathogens.

  16. Zika virus infections: An overview of current scenario.

    PubMed

    Dasti, Javid Iqbal

    2016-07-01

    Zika virus (ZIKV) was discovered more than half a century ago, recently it has gained unprecedented attention by the global health community. Until 2007, only 14 cases of human ZIKV infections were reported around the globe, while during the current outbreak, estimated cases mounted to approximately 1.5 million in Brazil alone, the virus was disseminated to wider South-American territories and travel-associated ZIKV infections were reported in USA, Europe and recently in China. ZIKV infections remain asymptomatic in approximately 80% of the individuals, and no anti-viral treatments were recommended. Yet, neurological complications associated with the infections, such as infant microcephaly and Guillain-Barré syndrome are major cause of the concern. Although, based on small numbers of cases, existing evidence strongly supports an exclusive link of viral infection and observed neurological complications. However, much work remains to assign exact numbers of complications caused by ZIKV. Regarding its structural attributes ZIKV shows remarkable resemblance with dengue virus and West-Nile virus. Despite, genomes of different ZIKV strains have already been decoded; role of the viral components in infection process and particularly pathogenesis of the disease remain widely unclear. In vulnerable areas, most viable strategy to ensure public health safety is vector control and enhanced public awareness about the transmission of the disease.

  17. Innate immune targets of hepatitis B virus infection

    PubMed Central

    Zou, Zhi-Qiang; Wang, Li; Wang, Kai; Yu, Ji-Guang

    2016-01-01

    Approximately 400 million people are chronically infected with hepatitis B virus (HBV) globally despite the widespread immunization of HBV vaccine and the development of antiviral therapies. The immunopathogenesis of HBV infection is initiated and driven by complexed interactions between the host immune system and the virus. Host immune responses to viral particles and proteins are regarded as the main determinants of viral clearance or persistent infection and hepatocyte injury. Innate immune system is the first defending line of host preventing from virus invasion. It is acknowledged that HBV has developed active tactics to escape innate immune recognition or actively interfere with innate immune signaling pathways and induce immunosuppression, which favor their replication. HBV reduces the expression of pattern-recognition receptors in the innate immune cells in humans. Also, HBV may interrupt different parts of antiviral signaling pathways, leading to the reduced production of antiviral cytokines such as interferons that contribute to HBV immunopathogenesis. A full comprehension of the mechanisms as to how HBV inactivates various elements of the innate immune response to initiate and maintain a persistent infection can be helpful in designing new immunotherapeutic methods for preventing and eradicating the virus. In this review, we aimed to summarize different branches the innate immune targeted by HBV infection. The review paper provides evidence that multiple components of immune responses should be activated in combination with antiviral therapy to disrupt the tolerance to HBV for eliminating HBV infection. PMID:27330680

  18. Virus Infections on Prion Diseased Mice Exacerbate Inflammatory Microglial Response

    PubMed Central

    Lins, Nara; Mourão, Luiz; Trévia, Nonata; Passos, Aline; Farias, José Augusto; Assunção, Jarila; Bento-Torres, João; Consentino Kronka Sosthenes, Marcia; Diniz, José Antonio Picanço; Vasconcelos, Pedro Fernando da Costa

    2016-01-01

    We investigated possible interaction between an arbovirus infection and the ME7 induced mice prion disease. C57BL/6, females, 6-week-old, were submitted to a bilateral intrahippocampal injection of ME7 prion strain (ME7) or normal brain homogenate (NBH). After injections, animals were organized into two groups: NBH (n = 26) and ME7 (n = 29). At 15th week after injections (wpi), animals were challenged intranasally with a suspension of Piry arbovirus 0.001% or with NBH. Behavioral changes in ME7 animals appeared in burrowing activity at 14 wpi. Hyperactivity on open field test, errors on rod bridge, and time reduction in inverted screen were detected at 15th, 19th, and 20th wpi respectively. Burrowing was more sensitive to earlier hippocampus dysfunction. However, Piry-infection did not significantly affect the already ongoing burrowing decline in the ME7-treated mice. After behavioral tests, brains were processed for IBA1, protease-resistant form of PrP, and Piry virus antigens. Although virus infection in isolation did not change the number of microglia in CA1, virus infection in prion diseased mice (at 17th wpi) induced changes in number and morphology of microglia in a laminar-dependent way. We suggest that virus infection exacerbates microglial inflammatory response to a greater degree in prion-infected mice, and this is not necessarily correlated with hippocampal-dependent behavioral deficits. PMID:28003864

  19. Innate immune targets of hepatitis B virus infection.

    PubMed

    Zou, Zhi-Qiang; Wang, Li; Wang, Kai; Yu, Ji-Guang

    2016-06-18

    Approximately 400 million people are chronically infected with hepatitis B virus (HBV) globally despite the widespread immunization of HBV vaccine and the development of antiviral therapies. The immunopathogenesis of HBV infection is initiated and driven by complexed interactions between the host immune system and the virus. Host immune responses to viral particles and proteins are regarded as the main determinants of viral clearance or persistent infection and hepatocyte injury. Innate immune system is the first defending line of host preventing from virus invasion. It is acknowledged that HBV has developed active tactics to escape innate immune recognition or actively interfere with innate immune signaling pathways and induce immunosuppression, which favor their replication. HBV reduces the expression of pattern-recognition receptors in the innate immune cells in humans. Also, HBV may interrupt different parts of antiviral signaling pathways, leading to the reduced production of antiviral cytokines such as interferons that contribute to HBV immunopathogenesis. A full comprehension of the mechanisms as to how HBV inactivates various elements of the innate immune response to initiate and maintain a persistent infection can be helpful in designing new immunotherapeutic methods for preventing and eradicating the virus. In this review, we aimed to summarize different branches the innate immune targeted by HBV infection. The review paper provides evidence that multiple components of immune responses should be activated in combination with antiviral therapy to disrupt the tolerance to HBV for eliminating HBV infection.

  20. Novel clinical features of recurrent human respiratory syncytial virus infections.

    PubMed

    Yui, Ikuko; Fujino, Motoko; Sawada, Akihito; Nakayama, Tetsuo

    2014-09-01

    Children and elderly individuals are often infected easily and repeatedly with human respiratory syncytial virus (HRSV); however, the features of recurrent infection in the same individual are defined poorly. To clarify the clinical significance of repeated HRSV infections in relation to subgroup epidemiology, this study performed prospective and longitudinal analyses in children with lower respiratory tract infections over 20 consecutive epidemics between 1985 and 2005 at a pediatric outpatient clinic in Kawasaki, Japan. HRSV infections were confirmed by 2 types of reverse-transcription PCR. Samples obtained from patients with repeated infections were subjected to sequence analysis and cloning analysis. A total of 1,312 lower respiratory tract infections observed in 1,010 patients were diagnosed as HRSV infections. Repeated HRSV infections occurred in 208 of the 1,010 patients. Analysis of the patients with repeated infections revealed that children were often infected multiple times even within a single short epidemic. Some patients were re-infected with strains having the same or virtually identical N gene sequences. In patients infected more than 4 times, cloning analysis revealed more frequent dual infections with both subgroups (23.8%). The HRSV-A subgroup caused subsequent homologous infections more frequently than did HRSV-B; furthermore, HRSV-A infections provided no protection from a second homologous infection. In contrast, HRSV-B infections offered significant protection against a second homologous infection. Statistical analysis revealed alleviation of symptoms with a reduced rate of dyspnoeic attacks only in the group re-infected with homologous HRSV-A strains. Thus, this study elucidates new clinical features of recurrent HRSV infection.

  1. Distribution of avian influenza H5N1 viral RNA in tissues of AI-vaccinated and unvaccinated contact chickens after experimental infection.

    PubMed

    Hassan, Mohamed K; Kilany, Walid H; Abdelwhab, E M; Arafa, Abdel-Satar; Selim, Abdullah; Samy, Ahmed; Samir, M; Le Brun, Yvon; Jobre, Yilma; Aly, Mona M

    2012-05-01

    Avian influenza due to highly pathogenic avian influenza (HPAIV) H5N1 virus is not a food-borne illness but a serious panzootic disease with the potential to be pandemic. In this study, broiler chickens were vaccinated with commercial H5N1 or H5N2 inactivated vaccines prior to being challenged with an HPAIV H5N1 (clade 2.2.1 classic) virus. Challenged and non-challenged vaccinated chickens were kept together, and unvaccinated chickens served as contact groups. Post-challenge samples from skin and edible internal organs were collected from dead and sacrificed (after a 14-day observation period) birds and tested using qRT-PCR for virus detection and quantification. H5N1 vaccine protected chickens against morbidity, mortality and transmission. Virus RNA was not detected in the meat or edible organs of chickens vaccinated with H5N1 vaccine. Conversely, H5N2 vaccine did not confer clinical protection, and a significant virus load was detected in the meat and internal organs. Phylogenetic analysis showed that the H5N1 virus vaccine and challenge virus strains are closely related. The results of the present study strongly suggest a need for proper selection of vaccines and their routine evaluation against newly emergent field viruses. These actions will help to reduce human exposure to HPAIV H5N1 virus from both infected live birds and slaughtered poultry. In addition, rigorous preventive measures should be put in place in order to minimize the public-health risks of avian influenza at the human-animal interface.

  2. Quantitation of Productively Infected Monocytes and Macrophages of Simian Immunodeficiency Virus-Infected Macaques

    PubMed Central

    Avalos, Claudia R.; Price, Sarah L.; Forsyth, Ellen R.; Pin, Julia N.; Shirk, Erin N.; Bullock, Brandon T.; Queen, Suzanne E.; Li, Ming; Gellerup, Dane; O'Connor, Shelby L.; Zink, M. Christine; Mankowski, Joseph L.; Gama, Lucio

    2016-01-01

    ABSTRACT Despite the success of combined antiretroviral therapy (ART), human immunodeficiency virus (HIV) infection remains a lifelong infection because of latent viral reservoirs in infected patients. The contribution of CD4+ T cells to infection and disease progression has been extensively studied. However, during early HIV infection, macrophages in brain and other tissues are infected and contribute to tissue-specific diseases, such as encephalitis and dementia in brain and pneumonia in lung. The extent of infection of monocytes and macrophages has not been rigorously assessed with assays comparable to those used to study infection of CD4+ T cells and to evaluate the number of CD4+ T cells that harbor infectious viral genomes. To assess the contribution of productively infected monocytes and macrophages to HIV- and simian immunodeficiency virus (SIV)-infected cells in vivo, we developed a quantitative virus outgrowth assay (QVOA) based on similar assays used to quantitate CD4+ T cell latent reservoirs in HIV- and SIV-infected individuals in whom the infection is suppressed by ART. Myeloid cells expressing CD11b were serially diluted and cocultured with susceptible cells to amplify virus. T cell receptor β RNA was measured as a control to assess the potential contribution of CD4+ T cells in the assay. Virus production in the supernatant was quantitated by quantitative reverse transcription-PCR. Productively infected myeloid cells were detected in blood, bronchoalveolar lavage fluid, lungs, spleen, and brain, demonstrating that these cells persist throughout SIV infection and have the potential to contribute to the viral reservoir during ART. IMPORTANCE Infection of CD4+ T cells and their role as latent reservoirs have been rigorously assessed; however, the frequency of productively infected monocytes and macrophages in vivo has not been similarly studied. Myeloid cells, unlike lymphocytes, are resistant to the cytopathic effects of HIV. Moreover, tissue

  3. Infection of influenza virus neuraminidase-vaccinated mice with homologous influenza virus leads to strong protection against heterologous influenza viruses.

    PubMed

    He, Biao; Chang, Haiyan; Liu, Zhihua; Huang, Chaoyang; Liu, Xueying; Zheng, Dan; Fang, Fang; Sun, Bing; Chen, Ze

    2014-12-01

    Vaccination is the best measure to prevent influenza pandemics. Here, we studied the protective effect against heterologous influenza viruses, including A/reassortant/NYMC X-179A (pH1N1), A/Chicken/Henan/12/2004 (H5N1), A/Chicken/Jiangsu/7/2002 (H9N2) and A/Guizhou/54/89×A/PR/8/34 (A/Guizhou-X) (H3N2), in mice first vaccinated with a DNA vaccine of haemagglutinin (HA) or neuraminidase (NA) of A/PR/8/34 (PR8) and then infected with the homologous virus. We showed that PR8 HA or NA vaccination both protected mice against a lethal dose of the homologous virus; PR8 HA or NA DNA vaccination and then PR8 infection in mice offered poor or excellent protection, respectively, against a second, heterologous influenza virus challenge. In addition, before the second heterologous influenza infection, the highest antibody level against nucleoprotein (NP) and matrix (M1 and M2) proteins was found in the PR8 NA-vaccinated and PR8-infected group. The level of induced cellular immunity against NP and M1 showed a trend consistent with that seen in antibody levels. However, PR8 HA+NA vaccination and then PR8 infection resulted in limited protection against heterologous influenza virus challenge. Results of the present study demonstrated that infection of the homologous influenza virus in mice already immunized with a NA vaccine could provide excellent protection against subsequent infection of a heterologous influenza virus. These findings suggested that NA, a major antigen of influenza virus, could be an important candidate antigen for universal influenza vaccines.

  4. 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.

  5. Pneumonia Virus of Mice Severe Respiratory Virus Infection in a Natural Host

    PubMed Central

    Rosenberg, Helene F.; Domachowske, Joseph B.

    2008-01-01

    Pneumonia virus of mice (PVM; family Paramyxoviridae, genus Pneumovirus) is a natural mouse pathogen that is closely related to the human and bovine respiratory syncytial viruses. Among the prominent features of this infection, robust replication of PVM takes place in bronchial epithelial cells in response to a minimal virus inoculum. Virus replication in situ results in local production of proinflammatory cytokines (MIP-1α, MIP-2, MCP-1 and IFNγ) and granulocyte recruitment to the lung. If left unchecked, PVM infection and the ensuing inflammatory response ultimately lead to pulmonary edema, respiratory compromise and death. In this review, we consider the recent studies using the PVM model that have provided important insights into the role of the inflammatory response in the pathogenesis of severe respiratory virus infection. We also highlight several works that have elucidated acquired immune responses to this pathogen, including T cell responses and the development of humoral immunity. Finally, we consider several immunomodulatory strategies that have been used successfully to reduce morbidity and mortality when administered to PVM infected, symptomatic mice, and thus hold promise as realistic therapeutic strategies for severe respiratory virus infections in human subjects. PMID:18471897

  6. Targeting Viral Proteostasis Limits Influenza Virus, HIV, and Dengue Virus Infection.

    PubMed

    Heaton, Nicholas S; Moshkina, Natasha; Fenouil, Romain; Gardner, Thomas J; Aguirre, Sebastian; Shah, Priya S; Zhao, Nan; Manganaro, Lara; Hultquist, Judd F; Noel, Justine; Sachs, David; Sachs, David H; Hamilton, Jennifer; Leon, Paul E; Chawdury, Amit; Tripathi, Shashank; Melegari, Camilla; Campisi, Laura; Hai, Rong; Metreveli, Giorgi; Gamarnik, Andrea V; García-Sastre, Adolfo; Greenbaum, Benjamin; Simon, Viviana; Fernandez-Sesma, Ana; Krogan, Nevan J; Mulder, Lubbertus C F; van Bakel, Harm; Tortorella, Domenico; Taunton, Jack; Palese, Peter; Marazzi, Ivan

    2016-01-19

    Viruses are obligate parasites and thus require the machinery of the host cell to replicate. Inhibition of host factors co-opted during active infection is a strategy hosts use to suppress viral replication and a potential pan-antiviral therapy. To define the cellular proteins and processes required for a virus during infection is thus crucial to understanding the mechanisms of virally induced disease. In this report, we generated fully infectious tagged influenza viruses and used infection-based proteomics to identify pivotal arms of cellular signaling required for influenza virus growth and infectivity. Using mathematical modeling and genetic and pharmacologic approaches, we revealed that modulation of Sec61-mediated cotranslational translocation selectively impaired glycoprotein proteostasis of influenza as well as HIV and dengue viruses and led to inhibition of viral growth and infectivity. Thus, by studying virus-human protein-protein interactions in the context of active replication, we have identified targetable host factors for broad-spectrum antiviral therapies.

  7. Detection and diagnosis of rice-infecting viruses

    PubMed Central

    Uehara-Ichiki, Tamaki; Shiba, Takuya; Matsukura, Keiichiro; Ueno, Takanori; Hirae, Masahiro; Sasaya, Takahide

    2013-01-01

    Rice-infecting viruses have caused serious damage to rice production in Asian, American, and African countries, where about 30 rice viruses and diseases have been reported. To control these diseases, developing accurate, quick methods to detect and diagnose the viruses in the host plants and any insect vectors of the viruses is very important. Based on an antigen–antibody reaction, serological methods such as latex agglutination reaction and enzyme-linked immunosorbent assay have advanced to detect viral particles or major proteins derived from viruses. They aid in forecasting disease and surveying disease spread and are widely used for virus detection at plant protection stations and research laboratories. From the early 2000s, based on sequence information for the target virus, several other methods such as reverse transcription-polymerase chain reaction (RT-PCR) and reverse transcription-loop-mediated isothermal amplification have been developed that are sensitive, rapid, and able to differentiate closely related viruses. Recent techniques such as real-time RT-PCR can be used to quantify the pathogen in target samples and monitor population dynamics of a virus, and metagenomic analyses using next-generation sequencing and microarrays show potential for use in the diagnosis of rice diseases. PMID:24130554

  8. Marburg virus infection detected in a common African bat.

    PubMed

    Towner, Jonathan S; Pourrut, Xavier; Albariño, César G; Nkogue, Chimène Nze; Bird, Brian H; Grard, Gilda; Ksiazek, Thomas G; Gonzalez, Jean-Paul; Nichol, Stuart T; Leroy, Eric M

    2007-08-22

    Marburg and Ebola viruses can cause large hemorrhagic fever (HF) outbreaks with high case fatality (80-90%) in human and great apes. Identification of the natural reservoir of these viruses is one of the most important topics in this field and a fundamental key to understanding their natural history. Despite the discovery of this virus family almost 40 years ago, the search for the natural reservoir of these lethal pathogens remains an enigma despite numerous ecological studies. Here, we report the discovery of Marburg virus in a common species of fruit bat (Rousettus aegyptiacus) in Gabon as shown by finding virus-specific RNA and IgG antibody in individual bats. These Marburg virus positive bats represent the first naturally infected non-primate animals identified. Furthermore, this is the first report of Marburg virus being present in this area of Africa, thus extending the known range of the virus. These data imply that more areas are at risk for MHF outbreaks than previously realized and correspond well with a recently published report in which three species of fruit bats were demonstrated to be likely reservoirs for Ebola virus.

  9. Background review for diagnostic test development for Zika virus infection

    PubMed Central

    Charrel, Rémi N; Leparc-Goffart, Isabelle; Pas, Suzan; de Lamballerie, Xavier; Koopmans, Marion; Reusken, Chantal

    2016-01-01

    Abstract Objective To review the state of knowledge about diagnostic testing for Zika virus infection and identify areas of research needed to address the current gaps in knowledge. Methods We made a non-systematic review of the published literature about Zika virus and supplemented this with information from commercial diagnostic test kits and personal communications with researchers in European preparedness networks. The review covered current knowledge about the geographical spread, pathogen characteristics, life cycle and infection kinetics of the virus. The available molecular and serological tests and biosafety issues are described and discussed in the context of the current outbreak strain. Findings We identified the following areas of research to address current knowledge gaps: (i) an urgent assessment of the laboratory capacity and capability of countries to detect Zika virus; (ii) rapid and extensive field validation of the available molecular and serological tests in areas with and without Zika virus transmission, with a focus on pregnant women; (iii) monitoring the genomic diversity of circulating Zika virus strains; (iv) prospective studies into the virus infection kinetics, focusing on diagnostic sampling (specimen types, combinations and timings); and (v) developing external quality assessments for molecular and serological testing, including differential diagnosis for similar viruses and symptom clusters. The availability of reagents for diagnostic development (virus strains and antigens, quantified viral ribonucleic acid) needs to be facilitated. Conclusion An international laboratory response is needed, including preparation of protocols for prospective studies to address the most pressing information needs. PMID:27516635

  10. Immunology and Pathology of Arena Virus Infections.

    DTIC Science & Technology

    1992-04-15

    adapted PIC strain, adPIC , and the GP avirulent prototype PIC strain PIC3739. adPIC replicated jto higher titers than PIC3739 in macrophages infected in...bioactivity levels increased in the serum of adPIC but not PIC3739 infected GPs. Spleen TNF activity rose during the first week after infection by both... adPIC infected GP (day 11) showed augmented ,TNF production after LPS stimulation as compared with PIC3739 infected or uninfected cells. ,We now theorize

  11. Cowpea viruses: Effect of single and mixed infections on symptomatology and virus concentration

    PubMed Central

    Taiwo, Moni A; Kareem, Kehinde T; Nsa, Imade Y; D'A Hughes, Jackies

    2007-01-01

    Natural multiple viral infections of cultivated cowpeas have been reported in Nigeria. In this study, three Nigerian commercial cowpea cultivars ("Olo 11", "Oloyin" and "White") and two lines from the IITA (IT86D- 719 and TVU 76) were mechanically inoculated with Cowpea aphid-borne mosaic virus (CABMV), Bean southern mosaic virus (SBMV) and Cowpea mottle virus (CMeV) singly, as well as in all possible combinations at 10, 20 and 30 days after planting (DAP). Samples of leaves or stems were collected at 10, 20 and 30 days after inoculation (DAI) and analyzed for relative virus concentration by Enzyme-Linked Immunosrbent Assay. All the cultivars and lines {CVS/L} were susceptible to the viruses but the commercial CVS showed more severe symptoms and had relatively higher viral concentration. In single virus infections, CABMV which induced the most severe symptoms had absorbance values (at 405 nm) of 0.11 to 0.46 while SBMV and CMeV which induced moderate symptoms had virus titre of 0.74 to 1.99 and 0.11 to 0.90 respectively. Plants inoculated 10 DAP had significantly higher virus concentration than those inoculated 30 DAP. In mixed infections involving CABMV (10 DAP) apical necrosis and death were observed in commercial cultivars "Olo 11" and "White". Enhancement of CMeV titers were observed in plants infected with CMeV + CABMV. Multiple viral infections of cowpeas may result in complete yield loss, hence, the availability of seeds of cultivars with a high level of multiple virus resistance is recommended as a means of control. PMID:17900355

  12. Argonaute 2 Suppresses Japanese Encephalitis Virus Infection in Aedes aegypti.

    PubMed

    Sasaki, Toshinori; Kuwata, Ryusei; Hoshino, Keita; Isawa, Haruhiko; Sawabe, Kyoko; Kobayashi, Mutsuo

    2017-01-24

    There are three main innate immune mechanisms against viruses in mosquitoes. Infection with the flavivirus dengue virus is controlled by RNA interference (RNAi) and the JAK-STAT and Toll signaling pathways. This study showed that another flavivirus, Japanese encephalitis virus (JEV), did not invade the salivary glands of Aedes aegypti and that this may be a result of the innate immune resistance to the virus. Argonaute 2 (Ago2) plays a critical role in the RNAi pathway. To understand the mechanism of JEV resistance, we focused on Ago2 as a possible target of JEV. Here, we show that the expression of MyD88 (a mediator of Toll signaling) and Ago2 mRNAs was induced by JEV in the salivary glands of Ae. aegypti mosquitoes and that Ago2, JAK, and domeless (DOME) mRNAs were induced by JEV in the bodies of Ae. aegypti mosquitoes. Double-stranded (ds) Ago2 RNA enhanced JEV infection, and the virus was detected in salivary glands by immunofluorescence assay. In contrast, MyD88 dsRNA had no effect on JEV infection. These data suggest that Ago2 plays a crucial role in mediating the innate immune response of Ae. aegypti to JEV in a manner similar to that employed by dengue virus.

  13. Japanese encephalitis virus tropism in experimentally infected pigs.

    PubMed

    Ricklin, Meret E; Garcìa-Nicolàs, Obdulio; Brechbühl, Daniel; Python, Sylvie; Zumkehr, Beatrice; Posthaus, Horst; Oevermann, Anna; Summerfield, Artur

    2016-02-24

    Pigs are considered to be the main amplifying host for Japanese encephalitis virus (JEV), and their infection can correlate with human cases of disease. Despite their importance in the ecology of the virus as it relates to human cases of encephalitis, the pathogenesis of JEV in pigs remains obscure. In the present study, the localization and kinetics of virus replication were investigated in various tissues after experimental intravenous infection of pigs. The data demonstrate a rapid and broad spreading of the virus to the central nervous system (CNS) and various other organs. A particular tropism of JEV in pigs not only to the CNS but also for secondary lymphoid tissue, in particular the tonsils with the overall highest viral loads, was observed. In this organ, even 11 days post infection, the latest time point of the experiment, no apparent decrease in viral RNA loads and live virus was found despite the presence of a neutralizing antibody response. This was also well beyond the clinical and viremic phase. These results are of significance for the pathogenesis of JEV, and call for further experimental studies focusing on the cellular source and duration of virus replication in pigs.

  14. First study of different insect cells to triatoma virus infection.

    PubMed

    Susevich, María Laura; Marti, Gerardo Aníbal; Metz, Germán Ernesto; Echeverría, María Gabriela

    2015-04-01

    The use of viruses for biological control is a new option to be considered. The family Dicistroviridae, which affects only invertebrates, is one of the families that have been proposed for this purpose. The Triatoma virus (TrV), a member of this family, affects triatomine transmitters of Chagas disease, which is endemic in Latin America but also expanding its worldwide distribution. To this end, we attempted virus replication in Diptera, Aedes albopictus (clone C6/36) and Lepidoptera Spodoptera frugiperda (SF9, SF21) and High Five (H5) cell lines. The methodologies used were transfection process, direct inoculation (purified virus), and inoculation of purified virus with trypsin. Results were confirmed by SDS-PAGE, Western blotting, RT-PCR, electron microscopy, and immunofluorescence. According to the results obtained, further analysis of susceptibility/infection of H5 cells to TrV required to be studied.

  15. Neurologic Complications of Influenza B Virus Infection in Adults, Romania.

    PubMed

    Popescu, Corneliu P; Florescu, Simin A; Lupulescu, Emilia; Zaharia, Mihaela; Tardei, Gratiela; Lazar, Mihaela; Ceausu, Emanoil; Ruta, Simona M

    2017-04-01

    We characterized influenza B virus-related neurologic manifestations in an unusually high number of hospitalized adults at a tertiary care facility in Romania during the 2014-15 influenza epidemic season. Of 32 patients with a confirmed laboratory diagnosis of influenza B virus infection, neurologic complications developed in 7 adults (median age 31 years). These complications were clinically diagnosed as confirmed encephalitis (4 patients), possible encephalitis (2 patients), and cerebellar ataxia (1 patient). Two of the patients died. Virus sequencing identified influenza virus B (Yam)-lineage clade 3, which is representative of the B/Phuket/3073/2013 strain, in 4 patients. None of the patients had been vaccinated against influenza. These results suggest that influenza B virus can cause a severe clinical course and should be considered as an etiologic factor for encephalitis.

  16. Possible Association Between Zika Virus Infection and Microcephaly - Brazil, 2015.

    PubMed

    Schuler-Faccini, Lavinia; Ribeiro, Erlane M; Feitosa, Ian M L; Horovitz, Dafne D G; Cavalcanti, Denise P; Pessoa, André; Doriqui, Maria Juliana R; Neri, Joao Ivanildo; Neto, Joao Monteiro de Pina; Wanderley, Hector Y C; Cernach, Mirlene; El-Husny, Antonette S; Pone, Marcos V S; Serao, Cassio L C; Sanseverino, Maria Teresa V

    2016-01-29

    In early 2015, an outbreak of Zika virus, a flavivirus transmitted by Aedes mosquitoes, was identified in northeast Brazil, an area where dengue virus was also circulating. By September, reports of an increase in the number of infants born with microcephaly in Zika virus-affected areas began to emerge, and Zika virus RNA was identified in the amniotic fluid of two women whose fetuses had been found to have microcephaly by prenatal ultrasound. The Brazil Ministry of Health (MoH) established a task force to investigate the possible association of microcephaly with Zika virus infection during pregnancy and a registry for incident microcephaly cases (head circumference ≥2 standard deviations [SD] below the mean for sex and gestational age at birth) and pregnancy outcomes among women suspected to have had Zika virus infection during pregnancy. Among a cohort of 35 infants with microcephaly born during August-October 2015 in eight of Brazil's 26 states and reported to the registry, the mothers of all 35 had lived in or visited Zika virus-affected areas during pregnancy, 25 (71%) infants had severe microcephaly (head circumference >3 SD below the mean for sex and gestational age), 17 (49%) had at least one neurologic abnormality, and among 27 infants who had neuroimaging studies, all had abnormalities. Tests for other congenital infections were negative. All infants had a lumbar puncture as part of the evaluation and cerebrospinal fluid (CSF) samples were sent to a reference laboratory in Brazil for Zika virus testing; results are not yet available. Further studies are needed to confirm the association of microcephaly with Zika virus infection during pregnancy and to understand any other adverse pregnancy outcomes associated with Zika virus infection. Pregnant women in Zika virus-affected areas should protect themselves from mosquito bites by using air conditioning, screens, or nets when indoors, wearing long sleeves and pants, using permethrin-treated clothing and gear

  17. Seroepidemiology of Asymptomatic Dengue Virus Infection in Jeddah, Saudi Arabia

    PubMed Central

    Jamjoom, Ghazi A.; Azhar, Esam I.; Kao, Moujahid A.; Radadi, Raja M.

    2016-01-01

    BACKGROUND Although virologically confirmed dengue fever has been recognized in Jeddah, Saudi Arabia, since 1994, causing yearly outbreaks, no proper seroepidemiologic studies on dengue virus have been conducted in this region. Such studies can define the extent of infection by this virus and estimate the proportion that may result in disease. The aim of this study was to measure the seroprevalence of past dengue virus infection in healthy Saudi nationals from different areas in the city of Jeddah and to investigate demographic and environmental factors that may increase exposure to infection. METHODS Sera were collected from 1984 Saudi subjects attending primary health care centers in six districts of Jeddah. These included general patients of various ages seeking routine vaccinations, antenatal care or treatment of different illnesses excluding fever or suspected dengue. A number of blood donors were also tested. Serum samples were tested by enzyme immunoassay (EIA) for IgG antibodies to dengue viruses 1, 2, 3, 4. A questionnaire was completed for each patient recording various anthropometric data and factors that may indicate possible risk of exposure to mosquito bites and dengue infection. Patients with missing data and those who reported a history of dengue fever were excluded from analysis, resulting in a sample of 1939 patients to be analyzed. RESULTS The overall prevalence of dengue virus infection as measured by anti-dengue IgG antibodies from asymptomatic residents in Jeddah was 47.8% (927/1939) and 37% (68/184) in blood donors. Infection mostly did not result in recognizable disease, as only 19 of 1956 subjects with complete information (0.1%) reported having dengue fever in the past. Anti dengue seropositivity increased with age and was higher in males than females and in residents of communal housing and multistory buildings than in villas. One of the six districts showed significant increase in exposure rate as compared to the others. Availability of

  18. Measles virus induces persistent infection by autoregulation of viral replication

    PubMed Central

    Doi, Tomomitsu; Kwon, Hyun-Jeong; Honda, Tomoyuki; Sato, Hiroki; Yoneda, Misako; Kai, Chieko

    2016-01-01

    Natural infection with measles virus (MV) establishes lifelong immunity. Persistent infection with MV is likely involved in this phenomenon, as non-replicating protein antigens never induce such long-term immunity. Although MV establishes stable persistent infection in vitro and possibly in vivo, the mechanism by which this occurs is largely unknown. Here, we demonstrate that MV changes the infection mode from lytic to non-lytic and evades the innate immune response to establish persistent infection without viral genome mutation. We found that, in the persistent phase, the viral RNA level declined with the termination of interferon production and cell death. Our analysis of viral protein dynamics shows that during the establishment of persistent infection, the nucleoprotein level was sustained while the phosphoprotein and large protein levels declined. The ectopic expression of nucleoprotein suppressed viral replication, indicating that viral replication is self-regulated by nucleoprotein accumulation during persistent infection. The persistently infected cells were able to produce interferon in response to poly I:C stimulation, suggesting that MV does not interfere with host interferon responses in persistent infection. Our results may provide mechanistic insight into the persistent infection of this cytopathic RNA virus that induces lifelong immunity. PMID:27883010

  19. Consequence of Maternal Zika Virus Infection: A Narrative review.

    PubMed

    Niaz, Kamal; Abdollahi, Mohammad

    2016-10-18

    Zika virus (ZIKV) is a deadly flavivirus that has spread from Africa to Asia and European countries. The virus is associated with other viruses in the same genus or family, transmitted by the same mosquito species with known history of fatality. A sudden increase in the rate of infection from ZIKV has made it a global health concern, which necessitates close symptom monitoring, enhancing treatment options, and vaccine production. This paper reviewed current reports on birth defects associated with ZIKV, mode of transmission, body fluids containing the virus, diagnosis , possible preventive measures or treatments, and vaccine development. Google scholar was used as the major search engine for research and review articles, up to July, 2016. Search terms such as "ZIKV", "ZIKV infection", "ZIKV serotypes", "treatment of ZIKV infection", "co-infection with zika virus", "flavivirus", "microcephaly and zika", "birth defects and Zika", as well as "ZIKV vaccine" were used. ZIKV has been detected in several body fluids such as saliva, semen, blood, and amniotic fluid. This reveals the possibility of sexual and mother to child transmission. The ability of the virus to cross the placental barrier and the blood brain barrier (BBB) has been associated with birth defects such as microcephaly, ocular defects, and Guillian Barre syndrome (GBS). Preventive measures can reduce the spread and risk of the infection. Available treatments only target symptoms while vaccines are still under development. Birth defects are associated with ZIKV infection in pregnant women; hence the need for development of standard treatments, employment of strict preventive measures and development of effective vaccines.

  20. A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection

    PubMed Central

    Gammon, Don B; Duraffour, Sophie; Rozelle, Daniel K; Hehnly, Heidi; Sharma, Rita; Sparks, Michael E; West, Cara C; Chen, Ying; Moresco, James J; Andrei, Graciela; Connor, John H; Conte, Darryl; Gundersen-Rindal, Dawn E; Marshall, William L; Yates, John R; Silverman, Neal; Mello, Craig C

    2014-01-01

    Virus-host interactions drive a remarkable diversity of immune responses and countermeasures. We found that two RNA viruses with broad host ranges, vesicular stomatitis virus (VSV) and Sindbis virus (SINV), are completely restricted in their replication after entry into Lepidopteran cells. This restriction is overcome when cells are co-infected with vaccinia virus (VACV), a vertebrate DNA virus. Using RNAi screening, we show that Lepidopteran RNAi, Nuclear Factor-κB, and ubiquitin-proteasome pathways restrict RNA virus infection. Surprisingly, a highly conserved, uncharacterized VACV protein, A51R, can partially overcome this virus restriction. We show that A51R is also critical for VACV replication in vertebrate cells and for pathogenesis in mice. Interestingly, A51R colocalizes with, and stabilizes, host microtubules and also associates with ubiquitin. We show that A51R promotes viral protein stability, possibly by preventing ubiquitin-dependent targeting of viral proteins for destruction. Importantly, our studies reveal exciting new opportunities to study virus-host interactions in experimentally-tractable Lepidopteran systems. DOI: http://dx.doi.org/10.7554/eLife.02910.001 PMID:24966209

  1. Aerosol Stability and Respiratory Infectivity of Lassa Virus

    DTIC Science & Technology

    1982-01-01

    diVaIlabLjjo, Cd, /1 ------- t I- 2 Lassa virus , an arenavirus , is endemic in western Africa and causes a severe generalized hemorrhagic disease in human...guinea pigs to infection with Lassa virus (P. B. Jahrling et al., manuscript in preparation) and other arenaviruses (8) when the virus is presented by...Prog. Mod. Viral. 18:111-126. 4. Fabiyi. A. 1976. Lassa fever ( arenaviruses ) as a public health problem. Bull. PAHO. 100335-337. 5. Guyton. A. C. 1947

  2. Emerging concepts in immunity to hepatitis C virus infection.

    PubMed

    Rosen, Hugo R

    2013-10-01

    Since the discovery of hepatitis C virus (HCV) by molecular cloning almost a quarter of a century ago, unprecedented at the time because the virus had never been grown in cell culture or detected serologically, there have been impressive strides in many facets of our understanding of the natural history of the disease, the viral life cycle, the pathogenesis, and antiviral therapy. It is apparent that the virus has developed multiple strategies to evade immune surveillance and eradication. This Review covers what we currently understand of the temporal and spatial immunological changes within the human innate and adaptive host immune responses that ultimately determine the outcomes of HCV infection.

  3. Influenza A virus infection complicated by fatal myocarditis.

    PubMed

    Nolte, K B; Alakija, P; Oty, G; Shaw, M W; Subbarao, K; Guarner, J; Shieh, W J; Dawson, J E; Morken, T; Cox, N J; Zaki, S R

    2000-12-01

    Influenza virus typically causes a febrile respiratory illness, but it can present with a variety of other clinical manifestations. We report a fatal case of myocarditis associated with influenza A infection. A previously healthy 11-year-old girl had malaise and fever for approximately 1 week before a sudden, witnessed fatal collapse at home. Autopsy revealed a pericardial effusion, a mixed lymphocytic and neutrophilic myocarditis, a mild lymphocytic interstitial pneumonia, focal bronchial/bronchiolar mucosal necrosis, and histologic changes consistent with asthma. Infection with influenza A (H3N2) was confirmed by virus isolation from a postmortem nasopharyngeal swab. Attempts to isolate virus from heart and lung tissue were unsuccessful. Immunohistochemical tests directed against influenza A antigens and in situ hybridization for influenza A genetic material demonstrated positive staining in bronchial epithelial cells, whereas heart sections were negative. Sudden death is a rare complication of influenza and may be caused by myocarditis. Forensic pathologists should be aware that postmortem nasopharyngeal swabs for viral culture and immunohistochemical or in situ hybridization procedures on lung tissue might be necessary to achieve a diagnosis. Because neither culturable virus nor influenza viral antigen could be identified in heart tissue, the pathogenesis of influenza myocarditis in this case is unlikely to be the result of direct infection of myocardium by the virus. The risk factors for developing myocarditis during an influenza infection are unknown.

  4. Insights into human immunodeficiency virus-hepatitis B virus co-infection in India

    PubMed Central

    Chakravarty, Runu; Pal, Ananya

    2015-01-01

    Shared routes of transmission lead to frequent human immunodeficiency virus (HIV)-hepatitis B virus (HBV) co-infection in a host which results in about 10% of HIV positive individuals to have chronic hepatitis B infection worldwide. In post-antiretroviral therapy era, liver diseases have emerged as the leading cause of morbidity and mortality in HIV-infected individuals and HBV co-infection have become the major health issue among this population particularly from the regions with endemic HBV infection. In setting of HIV-HBV co-infection, HIV significantly impacts the natural history of HBV infection, its disease profile and the treatment outcome in negative manner. Moreover, the epidemiological pattern of HBV infection and the diversity in HBV genome (genotypic and phenotypic) are also varied in HIV co-infected subjects as compared to HBV mono-infected individuals. Several reports on the abovementioned issues are available from developed parts of the world as well as from sub-Saharan African countries. In contrast, most of these research areas remained unexplored in India despite having considerable burden of HIV and HBV infections. This review discusses present knowledge from the studies on HIV-HBV co-infection in India and relevant reports from different parts of the world. Issues needed for the future research relevant to HIV-HBV co-infection in India are also highlighted here, including a call for further investigations on this field of study. PMID:26279986

  5. Epidemic polyarthritis (Ross River) virus infection in the Cook Islands.

    PubMed

    Rosen, L; Gubler, D J; Bennett, P H

    1981-11-01

    An epidemic of Ross River virus infection occurred in the Cook Islands early in 1980 and affected the majority of the inhabitants of Rarotonga, the most populated island in the group. This represents the easternmost extension of the virus which, until 1979, was believed limited to Australia, New Guinea, and the Solomon Islands. The clinical manifestations of Ross River disease, predominantly polyarthritis, did not differ significantly from those observed previously in Australia. However, unlike the experience in Australia, where Ross River virus has never been isolated from a patient with polyarthritis, the agent was recovered from the serum of one-half of approximately 100 such patients with serologically proven infections. It is not known if this latter observation is the result of a change in the virus, the different virus isolation technique employed, or other factors. It was found that the incubation period of the disease could be as short as 3 days--much less than previously suspected. Ross River virus was isolated from six pools of Aedes polynesiensis mosquitoes collected in nature and it appeared that this species was the most probable vector on Rarotonga. In view of the widespread distribution of Ae. polynesiensis on islands, in the eastern Pacific it would not be surprising if Ross River virus occurs in other previously unaffected areas in the future.

  6. Insights into Head-Tailed Viruses Infecting Extremely Halophilic Archaea

    PubMed Central

    Pietilä, Maija K.; Laurinmäki, Pasi; Russell, Daniel A.; Ko, Ching-Chung; Jacobs-Sera, Deborah; Butcher, Sarah J.

    2013-01-01

    Extremophilic archaea, both hyperthermophiles and halophiles, dominate in habitats where rather harsh conditions are encountered. Like all other organisms, archaeal cells are susceptible to viral infections, and to date, about 100 archaeal viruses have been described. Among them, there are extraordinary virion morphologies as well as the common head-tailed viruses. Although approximately half of the isolated archaeal viruses belong to the latter group, no three-dimensional virion structures of these head-tailed viruses are available. Thus, rigorous comparisons with bacteriophages are not yet warranted. In the present study, we determined the genome sequences of two of such viruses of halophiles and solved their capsid structures by cryo-electron microscopy and three-dimensional image reconstruction. We show that these viruses are inactivated, yet remain intact, at low salinity and that their infectivity is regained when high salinity is restored. This enabled us to determine their three-dimensional capsid structures at low salinity to a ∼10-Å resolution. The genetic and structural data showed that both viruses belong to the same T-number class, but one of them has enlarged its capsid to accommodate a larger genome than typically associated with a T=7 capsid by inserting an additional protein into the capsid lattice. PMID:23283946

  7. Beet western yellows virus infects the carnivorous plant Nepenthes mirabilis.

    PubMed

    Miguel, Sissi; Biteau, Flore; Mignard, Benoit; Marais, Armelle; Candresse, Thierry; Theil, Sébastien; Bourgaud, Frédéric; Hehn, Alain

    2016-08-01

    Although poleroviruses are known to infect a broad range of higher plants, carnivorous plants have not yet been reported as hosts. Here, we describe the first polerovirus naturally infecting the pitcher plant Nepenthes mirabilis. The virus was identified through bioinformatic analysis of NGS transcriptome data. The complete viral genome sequence was assembled from overlapping PCR fragments and shown to share 91.1 % nucleotide sequence identity with the US isolate of beet western yellows virus (BWYV). Further analysis of other N. mirabilis plants revealed the presence of additional BWYV isolates differing by several insertion/deletion mutations in ORF5.

  8. A case of Mayaro virus infection imported from French Guiana.

    PubMed

    Llagonne-Barets, Marion; Icard, Vinca; Leparc-Goffart, Isabelle; Prat, Christine; Perpoint, Thomas; André, Patrice; Ramière, Christophe

    2016-04-01

    Emergence of arboviruses is a rising problem in several areas in the world. Here we report a case of Mayaro virus infection that was diagnosed in a French citizen presenting a dengue-like syndrome with prolonged arthralgia following a travel in French Guiana. Diagnosis was based on serological testing, a newly developed specific RT-PCR and sequencing. The real incidence of this viral infection among travelers is poorly known but this case is the first reported in a European area where Aedes albopictus mosquitoes are established, which underscores the necessity to determine the vector competence of the European strain of this mosquito species for Mayaro virus.

  9. [Vaccination and serologic markers of hepatitis B virus infection].

    PubMed

    Salmeron Garcia, F; Echevarria Mayo, J M

    1990-01-01

    As a result of the Decree regulating the use of the Hepatitis B vaccination having been repealed, the usefulness of the study of infection markers for said virus prior to vaccination has been reviewed. The significance of the presence of isolated infection markers (surface antigen and antibodies as opposed to the surface antigens and those of the core of the Hepatitis B virus), and a sequential type study is discussed. It is considered that vaccination must be recommended whenever it is not possible to demonstrate the simultaneous presence of the surface antigen and antibodies as opposed to the core antigen or said antibodies and those corresponding to the surface antigen.

  10. Hepatitis C Virus Infection: Looking for Interferon Free Regimens

    PubMed Central

    González-Moreno, J.; Payeras-Cifre, A.

    2013-01-01

    Recent developments of new drugs' combinations are changing the treatment paradigm in hepatitis C virus infection. Due to the side effect profile of pegylated interferons, interferon-sparing regimens have become the main target in chronic hepatitis C treatment research. Recent proofs of concept studies have suggested that cure of chronic hepatitis C can be achieved without interferon. The purpose of this paper is to provide an overview of the clinical results recently reported for the treatment of hepatitis C virus infection with interferon-free regimens, focusing on the most promising new compounds and combinations. PMID:23710151

  11. Multiphasic acute disseminated encephalomyelitis associated with atypical rubella virus infection.

    PubMed

    Shinoda, Koji; Asahara, Hideaki; Uehara, Taira; Miyoshi, Katsue; Suzuki, Satoshi O; Iwaki, Toru; Kira, Jun-ichi

    2015-02-01

    We report the first case of an occurrence of multiphasic acute disseminated encephalomyelitis (ADEM) associated with atypical rubella virus infection with no rash and long-term increased titers of serum anti-rubella IgM in a 17-year-old male who had no history of rubella vaccination. He suffered from at least six clinical exacerbations with disseminated hyperintense lesions on FLAIR MR images during the course of 18 months. Repeated methylprednisolone pulse therapy and intravenous immunoglobulin therapy resolved the exacerbations. In patients with multiphasic ADEM of unknown etiology, clinicians should also consider the possibility of preceding infection with rubella virus.

  12. The Human Immunodeficiency Virus: Infectivity and Mechanisms of Pathogenesis

    NASA Astrophysics Data System (ADS)

    Fauci, Anthony S.

    1988-02-01

    Infection with the human immunodeficiency virus (HIV) results in a profound immunosuppression due predominantly to a selective depletion of helper/inducer T lymphocytes that express the receptor for the virus (the CD4 molecule). HIV also has tropism for the brain leading to neuropsychiatric abnormalities. Besides inducing cell death, HIV can interfere with T4 cell function by various mechanisms. The monocyte serves as a reservoir for HIV and is relatively refractory to its cytopathic effects. HIV can exist in a latent or chronic form which can be converted to a productive infection by a variety of inductive signals.

  13. Plasmacytoid dendritic cells sense hepatitis C virus-infected cells, produce interferon, and inhibit infection.

    PubMed

    Takahashi, Ken; Asabe, Shinichi; Wieland, Stefan; Garaigorta, Urtzi; Gastaminza, Pablo; Isogawa, Masanori; Chisari, Francis V

    2010-04-20

    Hepatitis C virus (HCV), a member of the Flaviviridae family, is a single-stranded positive-sense RNA virus that infects >170 million people worldwide and causes acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Despite its ability to block the innate host response in infected hepatocyte cell lines in vitro, HCV induces a strong type 1 interferon (IFN) response in the infected liver. The source of IFN in vivo and how it is induced are currently undefined. Here we report that HCV-infected cells trigger a robust IFN response in plasmacytoid dendritic cells (pDCs) by a mechanism that requires active viral replication, direct cell-cell contact, and Toll-like receptor 7 signaling, and we show that the activated pDC supernatant inhibits HCV infection in an IFN receptor-dependent manner. Importantly, the same events are triggered by HCV subgenomic replicon cells but not by free virus particles, suggesting the existence of a novel cell-cell RNA transfer process whereby HCV-infected cells can activate pDCs to produce IFN without infecting them. These results may explain how HCV induces IFN production in the liver, and they reveal a heretofore unsuspected aspect of the innate host response to viruses that can subvert the classical sensing machinery in the cells they infect, and do not infect or directly activate pDCs.

  14. Adaptive immune response during hepatitis C virus infection.

    PubMed

    Larrubia, Juan Ramón; Moreno-Cubero, Elia; Lokhande, Megha Uttam; García-Garzón, Silvia; Lázaro, Alicia; Miquel, Joaquín; Perna, Cristian; Sanz-de-Villalobos, Eduardo

    2014-04-07

    Hepatitis C virus (HCV) infection affects about 170 million people worldwide and it is a major cause of liver cirrhosis and hepatocellular carcinoma. HCV is a hepatotropic non-cytopathic virus able to persist in a great percentage of infected hosts due to its ability to escape from the immune control. Liver damage and disease progression during HCV infection are driven by both viral and host factors. Specifically, adaptive immune response carries out an essential task in controlling non-cytopathic viruses because of its ability to recognize infected cells and to destroy them by cytopathic mechanisms and to eliminate the virus by non-cytolytic machinery. HCV is able to impair this response by several means such as developing escape mutations in neutralizing antibodies and in T cell receptor viral epitope recognition sites and inducing HCV-specific cytotoxic T cell anergy and deletion. To impair HCV-specific T cell reactivity, HCV affects effector T cell regulation by modulating T helper and Treg response and by impairing the balance between positive and negative co-stimulatory molecules and between pro- and anti-apoptotic proteins. In this review, the role of adaptive immune response in controlling HCV infection and the HCV mechanisms to evade this response are reviewed.

  15. Review: Occult hepatitis C virus infection: still remains a controversy.

    PubMed

    Vidimliski, Pavlina Dzekova; Nikolov, Igor; Geshkovska, Nadica Matevska; Dimovski, Aleksandar; Rostaing, Lionel; Sikole, Aleksandar

    2014-09-01

    Occult hepatitis C virus (HCV) infection is characterized by the presence of HCV RNA in the liver cells or peripheral blood mononuclear cells of the patients whose serum samples test negative for HCV RNA, with or without presence of HCV antibodies. The present study reviews the existing literature on the persistence of occult hepatitis C virus infection, with description of the clinical characteristics and methods for identification of occult hepatitis C. Occult hepatitis C virus infection was detected in patients with abnormal results of liver function tests of unknown origin, with HCV antibodies and HCV RNA negativity in serum, and also in patients with spontaneous or treatment-induced recovery from hepatitis C. The viral replication in the liver cells and/or peripheral blood mononuclear cells was present in all clinical presentations of occult hepatitis C. The peripheral blood mononuclear cells represent an extra-hepatic site of HCV replication. The reason why HCV RNA was not detectable in the serum of patients with occult hepatitis C, could be the low number of circulating viral particles not detectable by the diagnostic tests with low sensitivity. It is uncertain whether occult hepatitis C is a different clinical entity or just a form of chronic hepatitis C virus infection. Data accumulated over the last decade demonstrated that an effective approach to the diagnosis of HCV infection would be the implementation of more sensitive HCV RNA diagnostic assays, and also, examination of the presence of viral particles in the cells of the immune system.

  16. [Potential neurocognitive consequences of infection by human respiratory syncytial virus].

    PubMed

    Flores, Juan Carlos; Bohmwald, Karen; Espinoza, Janyra; Jara, Crlstlna; Peña, Marcela; Hoyos-Bachiloglu, Rodrigo; Iturriaga, Carolina; Kalergis, Alexis M; Borzutzky, Arturo

    2016-10-01

    Human respiratory syncytial virus (RSV) infection remains as a major cause of morbidity and mortality among pediatric population. Immune response is poor and unable to establish a long term effective protection against this virus. Of particular interest has been the description of extrapulmonary manifestations of RSV infection in liver, kidney, endocrine system, heart and brain, associated to infection of peripheral blood. In the central nervous system (CNS), recent studies in animals have suggested long term neurocognitive impairment due to a direct damage from the virus. This was prevented in rats by a recombinant BCG vaccine expressing a nucleoprotein N of RSV that produces an effective immune response against the virus, not allowing its dissemination to the CNS. These findings in animal models highlight the importance of conducting more specific studies in children affected with severe infection by RSV. Therefore, our group is currently conducting an assessment of the possible long-term cognitive impairment in children under 2 years. The results of this study could be a strong argument to continue looking for an effective method for protecting against RSV infection.

  17. The heat shock response restricts virus infection in Drosophila

    PubMed Central

    Merkling, Sarah H.; Overheul, Gijs J.; van Mierlo, Joël T.; Arends, Daan; Gilissen, Christian; van Rij, Ronald P.

    2015-01-01

    Innate immunity is the first line of defence against pathogens and is essential for survival of the infected host. The fruit fly Drosophila melanogaster is an emerging model to study viral pathogenesis, yet antiviral defence responses remain poorly understood. Here, we describe the heat shock response, a cellular mechanism that prevents proteotoxicity, as a component of the antiviral immune response in Drosophila. Transcriptome analyses of Drosophila S2 cells and adult flies revealed strong induction of the heat shock response upon RNA virus infection. Dynamic induction patterns of heat shock pathway components were characterized in vitro and in vivo following infection with different classes of viruses. The heat shock transcription factor (Hsf), as well as active viral replication, were necessary for the induction of the response. Hsf-deficient adult flies were hypersensitive to virus infection, indicating a role of the heat shock response in antiviral defence. In accordance, transgenic activation of the heat shock response prolonged survival time after infection and enabled long-term control of virus replication to undetectable levels. Together, our results establish the heat shock response as an important constituent of innate antiviral immunity in Drosophila. PMID:26234525

  18. Inhibition of apoptosis in human immunodeficiency virus-infected cells enhances virus production and facilitates persistent infection.

    PubMed Central

    Antoni, B A; Sabbatini, P; Rabson, A B; White, E

    1995-01-01

    Apoptosis is one of several mechanisms by which human immunodeficiency virus type 1 (HIV-1) exerts its cytopathic effects. CD4+ Jurkat T-cell lines overexpressing the adenovirus E1B 19K protein, a potent inhibitor of apoptosis, were used to examine the consequences of inhibition of apoptosis during acute and chronic HIV-1 infections. E1B 19K protein expression inhibited HIV-induced apoptosis, enhanced virus production, and established high levels of persistent viral infection. One E1B 19K-expressing line appeared to undergo HIV-induced death via a nonapoptotic mechanism, illustrating that HIV infection results in lymphocyte depletion through multiple pathways. Increased virus production associated with sustained cell viability suggests that therapeutic approaches involving inhibition of HIV-induced programmed cell death may be problematic. PMID:7884884

  19. Tacaribe Virus but Not Junin Virus Infection Induces Cytokine Release from Primary Human Monocytes and Macrophages

    PubMed Central

    Groseth, Allison; Hoenen, Thomas; Weber, Michaela; Wolff, Svenja; Herwig, Astrid; Kaufmann, Andreas; Becker, Stephan

    2011-01-01

    The mechanisms underlying the development of disease during arenavirus infection are poorly understood. However, common to all hemorrhagic fever diseases is the involvement of macrophages as primary target cells, suggesting that the immune response in these cells may be of paramount importance during infection. Thus, in order to identify features of the immune response that contribute to arenavirus pathogenesis, we have examined the growth kinetics and cytokine profiles of two closely related New World arenaviruses, the apathogenic Tacaribe virus (TCRV) and the hemorrhagic fever-causing Junin virus (JUNV), in primary human monocytes and macrophages. Both viruses grew robustly in VeroE6 cells; however, TCRV titres were decreased by approximately 10 fold compared to JUNV in both monocytes and macrophages. Infection of both monocytes and macrophages with TCRV also resulted in the release of high levels of IL-6, IL-10 and TNF-α, while levels of IFN-α, IFN-β and IL-12 were not affected. However, we could show that the presence of these cytokines had no direct effect on growth of either TCRV of JUNV in macrophages. Further analysis also showed that while the production of IL-6 and IL-10 are dependent on viral replication, production of TNF-α also occurs after exposure to UV-inactivated TCRV particles and is thus independent of productive virus infection. Surprisingly, JUNV infection did not have an effect on any of the cytokines examined indicating that, in contrast to other viral hemorrhagic fever viruses, macrophage-derived cytokine production is unlikely to play an active role in contributing to the cytokine dysregulation observed in JUNV infected patients. Rather, these results suggest that an early, controlled immune response by infected macrophages may be critical for the successful control of infection of apathogenic viruses and prevention of subsequent disease, including systemic cytokine dysregulation. PMID:21572983

  20. Screening for Hepatitis B Virus Infection in Nonpregnant Adolescents and Adults

    MedlinePlus

    ... Screening for Hepatitis B Virus Infection in Nonpregnant Adolescents and Adults The U.S. Preventive Services Task Force ( ... Screening for Hepatitis B Virus Infection in Nonpregnant Adolescents and Adults. This final recommendation statement applies only ...

  1. Microglial activation induces neuronal death in Chandipura virus infection

    PubMed Central

    Verma, Abhishek Kumar; Ghosh, Sourish; Pradhan, Sreeparna; Basu, Anirban

    2016-01-01

    Neurotropic viruses induce neurodegeneration either directly by activating host death domains or indirectly through host immune response pathways. Chandipura Virus (CHPV) belonging to family Rhabdoviridae is ranked among the emerging pathogens of the Indian subcontinent. Previously we have reported that CHPV induces neurodegeneration albeit the root cause of this degeneration is still an open question. In this study we explored the role of microglia following CHPV infection. Phenotypic analysis of microglia through lectin and Iba-1 staining indicated cells were in an activated state post CHPV infection in cortical region of the infected mouse brain. Cytokine Bead Array (CBA) analysis revealed comparatively higher cytokine and chemokine levels in the same region. Increased level of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), Nitric Oxide (NO) and Reactive Oxygen species (ROS) in CHPV infected mouse brain indicated a strong inflammatory response to CHPV infection. Hence it was hypothesized through our analyses that this inflammatory response may stimulate the neuronal death following CHPV infection. In order to validate our hypothesis supernatant from CHPV infected microglial culture was used to infect neuronal cell line and primary neurons. This study confirmed the bystander killing of neurons due to activation of microglia post CHPV infection. PMID:26931456

  2. Macrophages in Progressive Human Immunodeficiency Virus/Simian Immunodeficiency Virus Infections

    PubMed Central

    DiNapoli, Sarah R.; Hirsch, Vanessa M.

    2016-01-01

    The cells that are targeted by primate lentiviruses (HIV and simian immunodeficiency virus [SIV]) are of intense interest given the renewed effort to identify potential cures for HIV. These viruses have been reported to infect multiple cell lineages of hematopoietic origin, including all phenotypic and functional CD4 T cell subsets. The two most commonly reported cell types that become infected in vivo are memory CD4 T cells and tissue-resident macrophages. Though viral infection of CD4 T cells is routinely detected in both HIV-infected humans and SIV-infected Asian macaques, significant viral infection of macrophages is only routinely observed in animal models wherein CD4 T cells are almost entirely depleted. Here we review the roles of macrophages in lentiviral disease progression, the evidence that macrophages support viral replication in vivo, the animal models where macrophage-mediated replication of SIV is thought to occur, how the virus can interact with macrophages in vivo, pathologies thought to be attributed to viral replication within macrophages, how viral replication in macrophages might contribute to the asymptomatic phase of HIV/SIV infection, and whether macrophages represent a long-lived reservoir for the virus. PMID:27307568

  3. Hepatitis C virus infection: knowledge in the orthopedic community.

    PubMed

    Flowerdew, J M; McGrory, B J

    2000-04-01

    A survey with 14 questions pertaining to the natural history, infectiveness, and diagnosis and treatment of hepatitis C viral infection was given to all practicing orthopedic surgeons in Portland, Maine. Possible responses were "true," "false," or "don't know" to the 14 statements. A question regarding any interest in learning more about the hepatitis C virus was also posed. Most (82%, 23/28) surgeons completed the questionnaire. A total of 72% of the responses were either wrong or marked "don't know"; most (83%) of the respondents wanted to know more about the infection about hepatitis C viral infection. Not only are orthopedic surgeons at risk for exposure to this virus, but also they are often the first to notify a patient of a positive result after routine hepatitis C testing of autologous predonated blood. Education programs and journal reviews should be directed toward this goal.

  4. Transcriptome analysis of feline infectious peritonitis virus infection.

    PubMed

    Mehrbod, Parvaneh; Harun, Mohammad Syamsul Reza; Shuid, Ahmad Naqib; Omar, Abdul Rahman

    2015-01-01

    Feline infectious peritonitis (FIP) is a lethal systemic disease caused by FIP virus (FIPV). There are no effective vaccines or treatment available, and the virus virulence determinants and pathogenesis are not fully understood. Here, we describe the sequencing of RNA extracted from Crandell Rees Feline Kidney (CRFK) cells infected with FIPV using the Illumina next-generation sequencing approach. Bioinformatics analysis, based on Felis catus 2X annotated shotgun reference genome, using CLC bio Genome Workbench is used to map both control and infected cells. Kal's Z test statistical analysis is used to analyze the differentially expressed genes from the infected CRFK cells. In addition, RT-qPCR analysis is used for further transcriptional profiling of selected genes in infected CRFK cells and Peripheral Blood Mononuclear Cells (PBMCs) from healthy and FIP-diagnosed cats.

  5. Autophagy interaction with herpes simplex virus type-1 infection

    PubMed Central

    O'Connell, Douglas; Liang, Chengyu

    2016-01-01

    abstract More than 50% of the U.S. population is infected with herpes simplex virus type-I (HSV-1) and global infectious estimates are nearly 90%. HSV-1 is normally seen as a harmless virus but debilitating diseases can arise, including encephalitis and ocular diseases. HSV-1 is unique in that it can undermine host defenses and establish lifelong infection in neurons. Viral reactivation from latency may allow HSV-1 to lay siege to the brain (Herpes encephalitis). Recent advances maintain that HSV-1 proteins act to suppress and/or control the lysosome-dependent degradation pathway of macroautophagy (hereafter autophagy) and consequently, in neurons, may be coupled with the advancement of HSV-1-associated pathogenesis. Furthermore, increasing evidence suggests that HSV-1 infection may constitute a gradual risk factor for neurodegenerative disorders. The relationship between HSV-1 infection and autophagy manipulation combined with neuropathogenesis may be intimately intertwined demanding further investigation. PMID:26934628

  6. Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection

    PubMed Central

    Conway, Michael J.; Londono-Renteria, Berlin; Troupin, Andrea; Watson, Alan M.; Klimstra, William B.; Fikrig, Erol; Colpitts, Tonya M.

    2016-01-01

    Aedes aegypti is the primary vector of several medically relevant arboviruses including dengue virus (DENV) types 1–4. Ae. aegypti transmits DENV by inoculating virus-infected saliva into host skin during probing and feeding. Ae. aegypti saliva contains over one hundred unique proteins and these proteins have diverse functions, including facilitating blood feeding. Previously, we showed that Ae. aegypti salivary gland extracts (SGEs) enhanced dissemination of DENV to draining lymph nodes. In contrast, HPLC-fractionation revealed that some SGE components inhibited infection. Here, we show that D7 proteins are enriched in HPLC fractions that are inhibitory to DENV infection, and that recombinant D7 protein can inhibit DENV infection in vitro and in vivo. Further, binding assays indicate that D7 protein can directly interact with DENV virions and recombinant DENV envelope protein. These data reveal a novel role for D7 proteins, which inhibits arbovirus transmission to vertebrates through a direct interaction with virions. PMID:27632170

  7. Occupational hepatitis B virus infection in sewage workers.

    PubMed

    Arvanitidou, M; Constantinidis, T C; Doutsos, J; Mandraveli, K; Katsouyannopoulos, V

    1998-01-01

    In a cross-sectional study the employees of a Sewage Company were tested for hepatitis B virus (HBV) markers--HBsAg, anti-HBs, anti-HBc--to determine the prevalence of HBV infection and assess the risk of exposed sewage workers becoming infected, so as to evaluate the necessity for appropriate vaccination. The overall prevalence of HBV markers was 43.9% and 6.6% of the employees were HBsAg carriers. In the univariate analysis the prevalence of past and current infection was significantly associated with exposure to sewage (p < 0.001), age (p < 0.001) and with educational level (p < 0.001). However, the logistic regression analysis confirmed that only exposure to sewage was independently associated with positivity for HBV infection (p < 0.001). Workers exposed to sewage should therefore be considered for vaccination against hepatitis B virus.

  8. Autophagy interaction with herpes simplex virus type-1 infection.

    PubMed

    O'Connell, Douglas; Liang, Chengyu

    2016-01-01

    More than 50% of the U.S. population is infected with herpes simplex virus type-I (HSV-1) and global infectious estimates are nearly 90%. HSV-1 is normally seen as a harmless virus but debilitating diseases can arise, including encephalitis and ocular diseases. HSV-1 is unique in that it can undermine host defenses and establish lifelong infection in neurons. Viral reactivation from latency may allow HSV-1 to lay siege to the brain (Herpes encephalitis). Recent advances maintain that HSV-1 proteins act to suppress and/or control the lysosome-dependent degradation pathway of macroautophagy (hereafter autophagy) and consequently, in neurons, may be coupled with the advancement of HSV-1-associated pathogenesis. Furthermore, increasing evidence suggests that HSV-1 infection may constitute a gradual risk factor for neurodegenerative disorders. The relationship between HSV-1 infection and autophagy manipulation combined with neuropathogenesis may be intimately intertwined demanding further investigation.

  9. Diagnosis of Hepatitis A Virus Infection: a Molecular Approach

    PubMed Central

    Nainan, Omana V.; Xia, Guoliang; Vaughan, Gilberto; Margolis, Harold S.

    2006-01-01

    Current serologic tests provide the foundation for diagnosis of hepatitis A and hepatitis A virus (HAV) infection. Recent advances in methods to identify and characterize nucleic acid markers of viral infections have provided the foundation for the field of molecular epidemiology and increased our knowledge of the molecular biology and epidemiology of HAV. Although HAV is primarily shed in feces, there is a strong viremic phase during infection which has allowed easy access to virus isolates and the use of molecular markers to determine their genetic relatedness. Molecular epidemiologic studies have provided new information on the types and extent of HAV infection and transmission in the United States. In addition, these new diagnostic methods have provided tools for the rapid detection of food-borne HAV transmission and identification of the potential source of the food contamination. PMID:16418523

  10. Vaccinia virus infection & temporal analysis of virus gene expression: Part 3.

    PubMed

    Yen, Judy; Golan, Ron; Rubins, Kathleen

    2009-04-13

    The family Poxviridae consists of large double-stranded DNA containing viruses that replicate exclusively in the cytoplasm of infected cells. Members of the orthopox genus include variola, the causative agent of human small pox, monkeypox, and vaccinia (VAC), the prototypic member of the virus family. Within the relatively large (approximately 200 kb) vaccinia genome, three classes of genes are encoded: early, intermediate, and late. While all three classes are transcribed by virally-encoded RNA polymerases, each class serves a different function in the life cycle of the virus. Poxviruses utilize multiple strategies for modulation of the host cellular environment during infection. In order to understand regulation of both host and virus gene expression, we have utilized genome-wide approaches to analyze transcript abundance from both virus and host cells. Here, we demonstrate time course infections of HeLa cells with Vaccinia virus and sampling RNA at several time points post-infection. Both host and viral total RNA is isolated and amplified for hybridization to microarrays for analysis of gene expression.

  11. Vaccinia virus infection & temporal analysis of virus gene expression: part 1.

    PubMed

    Yen, Judy; Golan, Ron; Rubins, Kathleen

    2009-04-08

    The family Poxviridae consists of large double-stranded DNA containing viruses that replicate exclusively in the cytoplasm of infected cells. Members of the orthopox genus include variola, the causative agent of human small pox, monkeypox, and vaccinia (VAC), the prototypic member of the virus family. Within the relatively large (approximately 200 kb) vaccinia genome, three classes of genes are encoded: early, intermediate, and late. While all three classes are transcribed by virally-encoded RNA polymerases, each class serves a different function in the life cycle of the virus. Poxviruses utilize multiple strategies for modulation of the host cellular environment during infection. In order to understand regulation of both host and virus gene expression, we have utilized genome-wide approaches to analyze transcript abundance from both virus and host cells. Here, we demonstrate time course infections of HeLa cells with Vaccinia virus and sampling RNA at several time points post-infection. Both host and viral total RNA is isolated and amplified for hybridization to microarrays for analysis of gene expression.

  12. Vaccinia virus infection & temporal analysis of virus gene expression: Part 2.

    PubMed

    Yen, Judy; Golan, Ron; Rubins, Kathleen

    2009-04-10

    The family Poxviridae consists of large double-stranded DNA containing viruses that replicate exclusively in the cytoplasm of infected cells. Members of the orthopox genus include variola, the causative agent of human small pox, monkeypox, and vaccinia (VAC), the prototypic member of the virus family. Within the relatively large (approximately 200 kb) vaccinia genome, three classes of genes are encoded: early, intermediate, and late. While all three classes are transcribed by virally-encoded RNA polymerases, each class serves a different function in the life cycle of the virus. Poxviruses utilize multiple strategies for modulation of the host cellular environment during infection. In order to understand regulation of both host and virus gene expression, we have utilized genome-wide approaches to analyze transcript abundance from both virus and host cells. Here, we demonstrate time course infections of HeLa cells with Vaccinia virus and sampling RNA at several time points post-infection. Both host and viral total RNA is isolated and amplified for hybridization to microarrays for analysis of gene expression.

  13. Ganjam virus/Nairobi sheep disease virus induces a pro-inflammatory response in infected sheep.

    PubMed

    Bin Tarif, Abid; Lasecka, Lidia; Holzer, Barbara; Baron, Michael D

    2012-10-19

    Partly due to climate change, and partly due to changes of human habitat occupation, the impact of tick-borne viruses is increasing. Nairobi sheep disease virus (NSDV) and Ganjam virus (GV) are two names for the same virus, which causes disease in sheep and goats and is currently known to be circulating in India and East Africa. The virus is transmitted by ixodid ticks and causes a severe hemorrhagic disease. We have developed a real-time PCR assay for the virus genome and validated it in a pilot study of the pathogenicity induced by two different isolates of NSDV/GV. One isolate was highly adapted to tissue culture, grew in most cell lines tested, and was essentially apathogenic in sheep. The second isolate appeared to be poorly adapted to cell culture and retained pathogenicity in sheep. The real-time PCR assay for virus easily detected 4 copies or less of the viral genome, and allowed a quantitative measure of the virus in whole blood. Measurement of the changes in cytokine mRNAs showed similar changes to those observed in humans infected by the closely related virus Crimean Congo hemorrhagic fever virus.

  14. Experimental infection of vertebrates of the Pocomoke Cypress Swamp, Maryland with Keystone and Jamestown Canyon viruses.

    PubMed

    Watts, D M; Tammariello, R F; Dalrymple, J M; Eldridge, B F; Russell, P K; Top, F H

    1979-03-01

    Experimental studies were conducted to assess the susceptibility of white-tailed deer (Odocoileus virginianus), gray squirrels (Sciurus carolinensis), and cottontail rabbits (Sylvilagus floridanus) to Jamestown Canyon (JC) and/or Keystone (KEY) virus infection. Viremia occurred in 5 of 6 deer inoculated with JC virus; however, all deer developed KEY virus neutralizing antibody. Based on the observation that antibody elicited by primary infection of deer with either KEY or JC virus exhibited partial heterologous neutralization in vitro, cross-challenge experiments were performed in these animals. Keystone virus failed to infect deer 30 days post primary JC virus infection; however, deer became infected when challenged with KEY virus 80 days after the initial JC virus infection as indicated by a substantial increase in antibody titer. Similarly, JC virus failed to produce viremia in immune animals infected with KEY virus 80 days previously, although 2 of the 3 animals challenged had serological evidence of infection. Three field-collected cottontail rabbits with no evidence of KEY antibody were readily susceptible to KEY virus infection and developed viremias of 1-4 days' duration; rabbits with KEY virus antibody did not develop viremia upon KEY virus challenge. Eight antibody-negative field-collected gray squirrels became viremic following injection with KEY virus; however, a comparable group of squirrels did not become viremic when injected with JC virus.

  15. Ectromelia virus inhibitor of complement enzymes protects intracellular mature virus and infected cells from mouse complement.

    PubMed

    Moulton, Elizabeth A; Bertram, Paula; Chen, Nanhai; Buller, R Mark L; Atkinson, John P

    2010-09-01

    Poxviruses produce complement regulatory proteins to subvert the host's immune response. Similar to the human pathogen variola virus, ectromelia virus has a limited host range and provides a mouse model where the virus and the host's immune response have coevolved. We previously demonstrated that multiple components (C3, C4, and factor B) of the classical and alternative pathways are required to survive ectromelia virus infection. Complement's role in the innate and adaptive immune responses likely drove the evolution of a virus-encoded virulence factor that regulates complement activation. In this study, we characterized the ectromelia virus inhibitor of complement enzymes (EMICE). Recombinant EMICE regulated complement activation on the surface of CHO cells, and it protected complement-sensitive intracellular mature virions (IMV) from neutralization in vitro. It accomplished this by serving as a cofactor for the inactivation of C3b and C4b and by dissociating the catalytic domain of the classical pathway C3 convertase. Infected murine cells initiated synthesis of EMICE within 4 to 6 h postinoculation. The levels were sufficient in the supernatant to protect the IMV, upon release, from complement-mediated neutralization. EMICE on the surface of infected murine cells also reduced complement activation by the alternative pathway. In contrast, classical pathway activation by high-titer antibody overwhelmed EMICE's regulatory capacity. These results suggest that EMICE's role is early during infection when it counteracts the innate immune response. In summary, ectromelia virus produced EMICE within a few hours of an infection, and EMICE in turn decreased complement activation on IMV and infected cells.

  16. The Effects of High Temperature on Infection by Potato virus Y, Potato virus A, and Potato leafroll virus

    PubMed Central

    Chung, Bong Nam; Canto, Tomas; Tenllado, Francisco; Choi, Kyung San; Joa, Jae Ho; Ahn, Jeong Joon; Kim, Chun Hwan; Do, Ki Seck

    2016-01-01

    We examined the effects of temperature on acquisition of Potato virus Y-O (PVY-O), Potato virus A (PVA), and Potato leafroll virus (PLRV) by Myzus persicae by performing transmission tests with aphids that acquired each virus at different temperatures. Infection by PVY-O/PVA and PLRV increased with increasing plant temperature in Nicotiana benthamiana and Physalis floridana, respectively, after being transmitted by aphids that acquired them within a temperature range of 10–20°C. However, infection rates subsequently decreased. Direct qRT-PCR of RNA extracted from a single aphid showed that PLRV infection increased in the 10–20°C range, but this trend also declined shortly thereafter. We examined the effect of temperature on establishment of virus infection. The greatest number of plants became infected when N. benthamiana was held at 20°C after inoculation with PVY-O or PVA. The largest number of P. floridana plants became infected with PLRV when the plants were maintained at 25°C. PLRV levels were highest in P. floridana kept at 20–25°C. These results indicate that the optimum temperatures for proliferation of PVY-O/PVA and PLRV differed. Western blot analysis showed that accumulations of PVY-O and PVA coat proteins (CPs) were lower at 10°C or 15°C than at 20°C during early infection. However, accumulation increased over time. At 25°C or 30°C, the CPs of both viruses accumulated during early infection but disappeared as time passed. Our results suggest that symptom attenuation and reduction of PVY-O and PVA CP accumulation at higher temperatures appear to be attributable to increased RNA silencing. PMID:27493607

  17. Genes determining the course of virus persistence in the liver: lessons from murine infection with lymphocytic choriomeningitis virus.

    PubMed

    Lang, Philipp A; Recher, Mike; Häussinger, Dieter; Lang, Karl S

    2010-01-01

    More than 500 million people worldwide are persistently infected with either hepatitis B virus (HBV) or hepatitis C virus (HCV). Although both viruses are poorly cytopathic, persistent infection causes severe immunopathologic damage to liver tissue; histologically, such damage is characterized by fatty liver disease, liver fibrosis, and a higher likelihood of hepatocellular carcinoma. Virus-specific CD8+ T cells play a crucial role during infection with hepatitis viruses. On the one hand, rapid activation of CD8+ T cells can control the virus and therefore inhibit its persistence. On the other hand, once the virus persists in the liver, the chronic activation of virus-specific T cells leads to continued liver cell damage. This double-edged role of CD8+ T cells determines the final outcome of infection. In half of cases of human HCV infection, the virus persists; in the other half, the virus is controlled. Additional insights into the molecular mechanisms that determine the course of the disease may be gained from the study of appropriate murine models. This review discusses the similarities and differences between infection with lymphocytic choriomeningitis virus (LCMV) in mice and chronic infection with hepatitis virus in humans.

  18. Vaccinia virus infection in monkeys, Brazilian Amazon.

    PubMed

    Abrahão, Jônatas S; Silva-Fernandes, André T; Lima, Larissa S; Campos, Rafael K; Guedes, Maria I M C; Cota, Marcela M G; Assis, Felipe L; Borges, Iara A; Souza-Júnior, Milton F; Lobato, Zélia I P; Bonjardim, Cláudio A; Ferreira, Paulo C P; Trindade, Giliane S; Kroon, Erna G

    2010-06-01

    To detect orthopoxvirus in the Brazilian Amazon, we conducted a serosurvey of 344 wild animals. Neutralizing antibodies against orthopoxvirus were detected by plaque-reduction neutralizing tests in 84 serum samples. Amplicons from 6 monkey samples were sequenced. These amplicons identified vaccinia virus genetically similar to strains from bovine vaccinia outbreaks in Brazil.

  19. Vaccinia Virus Infection in Monkeys, Brazilian Amazon

    PubMed Central

    Abrahão, Jônatas S.; Silva-Fernandes, André T.; Lima, Larissa S.; Campos, Rafael K.; Guedes, Maria I.M.C.; Cota, Marcela M.G.; Assis, Felipe L.; Borges, Iara A.; Souza-Júnior, Milton F.; Lobato, Zélia I.P.; Bonjardim, Cláudio A.; Ferreira, Paulo C.P.; Trindade, Giliane S.

    2010-01-01

    To detect orthopoxvirus in the Brazilian Amazon, we conducted a serosurvey of 344 wild animals. Neutralizing antibodies against orthopoxvirus were detected by plaque-reduction neutralizing tests in 84 serum samples. Amplicons from 6 monkey samples were sequenced. These amplicons identified vaccinia virus genetically similar to strains from bovine vaccinia outbreaks in Brazil. PMID:20507750

  20. Mayaro virus infection cycle relies on casein kinase 2 activity.

    PubMed

    Barroso, Madalena M S; Lima, Carla S; Silva-Neto, Mário A C; Da Poian, Andrea T

    2002-09-06

    Replication of Mayaro virus in Vero cells induces dramatic cytopathic effects and cell death. In this study, we have evaluated the role of casein kinase 2 (CK2) during Mayaro virus infection cycle. We found that CK2 was activated during the initial stages of infection ( approximately 36% after 4h). This activation was further confirmed when the enzyme was partially purified from the cellular lysate either by Mono Q 5/5Hr column or heparin-agarose column. Using this later column, we found that the elution profile of CK2 activity from infected cells was different from that obtained for control cell enzyme, suggesting a structural modification of CK2 after infection. Treatment of infected cells with a cell-permeable inhibitor of CK2, dichloro-1-(beta-D-ribofuranosyl)benzimidazole (DRB), abolished the cytopathic effect in a dose-dependent manner. Together this set of data demonstrates for the first time that CK2 activity in host cells is required in Mayaro virus infection cycle.

  1. Host sphingomyelin increases West Nile virus infection in vivo

    PubMed Central

    Martín-Acebes, Miguel A.; Gabandé-Rodríguez, Enrique; García-Cabrero, Ana M.; Sánchez, Marina P.; Ledesma, María Dolores; Sobrino, Francisco; Saiz, Juan-Carlos

    2016-01-01

    Flaviviruses, such as the dengue virus and the West Nile virus (WNV), are arthropod-borne viruses that represent a global health problem. The flavivirus lifecycle is intimately connected to cellular lipids. Among the lipids co-opted by flaviviruses, we have focused on SM, an important component of cellular membranes particularly enriched in the nervous system. After infection with the neurotropic WNV, mice deficient in acid sphingomyelinase (ASM), which accumulate high levels of SM in their tissues, displayed exacerbated infection. In addition, WNV multiplication was enhanced in cells from human patients with Niemann-Pick type A, a disease caused by a deficiency of ASM activity resulting in SM accumulation. Furthermore, the addition of SM to cultured cells also increased WNV infection, whereas treatment with pharmacological inhibitors of SM synthesis reduced WNV infection. Confocal microscopy analyses confirmed the association of SM with viral replication sites within infected cells. Our results unveil that SM metabolism regulates flavivirus infection in vivo and propose SM as a suitable target for antiviral design against WNV. PMID:26764042

  2. Innate immune responses in raccoons after raccoon rabies virus infection.

    PubMed

    Srithayakumar, Vythegi; Sribalachandran, Hariharan; Rosatte, Rick; Nadin-Davis, Susan A; Kyle, Christopher J

    2014-01-01

    Zoonotic wildlife diseases pose significant health risks not only to their primary vectors but also to humans and domestic animals. Rabies is a lethal encephalitis caused by rabies virus (RV). This RNA virus can infect a range of terrestrial mammals but each viral variant persists in a particular reservoir host. Active management of these host vectors is needed to minimize the negative impacts of this disease, and an understanding of the immune response to RV infection aids strategies for host vaccination. Current knowledge of immune responses to RV infection comes primarily from rodent models in which an innate immune response triggers activation of several genes and signalling pathways. It is unclear, however, how well rodent models represent the immune response of natural hosts. This study investigates the innate immune response of a primary host, the raccoon, to a peripheral challenge using the raccoon rabies virus (RRV). The extent and temporal course of this response during RRV infection was analysed using genes predicted to be upregulated during infection (IFNs; IFN regulatory factors; IL-6; Toll like receptor-3; TNF receptor). We found that RRV activated components of the innate immune system, with changes in levels of transcripts correlated with presence of viral RNA. Our results suggest that natural reservoirs of rabies may not mimic the immune response triggered in rodent models, highlighting the need for further studies of infection in primary hosts.

  3. Alteration of cell cycle progression by Sindbis virus infection

    SciTech Connect

    Yi, Ruirong; Saito, Kengo; Isegawa, Naohisa; Shirasawa, Hiroshi

    2015-07-10

    We examined the impact of Sindbis virus (SINV) infection on cell cycle progression in a cancer cell line, HeLa, and a non-cancerous cell line, Vero. Cell cycle analyses showed that SINV infection is able to alter the cell cycle progression in both HeLa and Vero cells, but differently, especially during the early stage of infection. SINV infection affected the expression of several cell cycle regulators (CDK4, CDK6, cyclin E, p21, cyclin A and cyclin B) in HeLa cells and caused HeLa cells to accumulate in S phase during the early stage of infection. Monitoring SINV replication in HeLa and Vero cells expressing cell cycle indicators revealed that SINV which infected HeLa cells during G{sub 1} phase preferred to proliferate during S/G{sub 2} phase, and the average time interval for viral replication was significantly shorter in both HeLa and Vero cells infected during G{sub 1} phase than in cells infected during S/G{sub 2} phase. - Highlights: • SINV infection was able to alter the cell cycle progression of infected cancer cells. • SINV infection can affect the expression of cell cycle regulators. • SINV infection exhibited a preference for the timing of viral replication among the cell cycle phases.

  4. Discovery of mammalian genes that participate in virus infection

    PubMed Central

    Organ, Edward L; Sheng, Jinsong; Ruley, H Earl; Rubin, Donald H

    2004-01-01

    Background Viruses are obligate intracellular parasites that rely upon the host cell for different steps in their life cycles. The characterization of cellular genes required for virus infection and/or cell killing will be essential for understanding viral life cycles, and may provide cellular targets for new antiviral therapies. Results Candidate genes required for lytic reovirus infection were identified by tagged sequence mutagenesis, a process that permits rapid identification of genes disrupted by gene entrapment. One hundred fifty-one reovirus resistant clones were selected from cell libraries containing 2 × 105 independently disrupted genes, of which 111 contained mutations in previously characterized genes and functionally anonymous transcription units. Collectively, the genes associated with reovirus resistance differed from genes targeted by random gene entrapment in that known mutational hot spots were under represented, and a number of mutations appeared to cluster around specific cellular processes, including: IGF-II expression/signalling, vesicular transport/cytoskeletal trafficking and apoptosis. Notably, several of the genes have been directly implicated in the replication of reovirus and other viruses at different steps in the viral lifecycle. Conclusions Tagged sequence mutagenesis provides a rapid, genome-wide strategy to identify candidate cellular genes required for virus infection. The candidate genes provide a starting point for mechanistic studies of cellular processes that participate in the virus lifecycle and may provide targets for novel anti-viral therapies. PMID:15522117

  5. Host Factors in the Infection Cycle of Bamboo mosaic virus

    PubMed Central

    Huang, Ying-Ping; Chen, I-Hsuan; Tsai, Ching-Hsiu

    2017-01-01

    To complete the infection cycle efficiently, the virus must hijack the host systems in order to benefit for all the steps and has to face all the defense mechanisms from the host. This review involves a discussion of how these positive and negative factors regulate the viral RNA accumulation identified for the Bamboo mosaic virus (BaMV), a single-stranded RNA virus. The genome of BaMV is approximately 6.4 kb in length, encoding five functional polypeptides. To reveal the host factors involved in the infection cycle of BaMV, a few different approaches were taken to screen the candidates. One of the approaches is isolating the viral replicase-associated proteins by co-immunoprecipitation with the transiently expressed tagged viral replicase in plants. Another approach is using the cDNA-amplified fragment length polymorphism technique to screen the differentially expressed genes derived from N. benthamiana plants after infection. The candidates are examined by knocking down the expression in plants using the Tobacco rattle virus-based virus-induced gene silencing technique following BaMV inoculation. The positive or negative regulators could be described as reducing or enhancing the accumulation of BaMV in plants when the expression levels of these proteins are knocked down. The possible roles of these host factors acting on the accumulation of BaMV will be discussed. PMID:28360904

  6. Potent neutralizing monoclonal antibodies against Ebola virus infection

    PubMed Central

    Zhang, Qi; Gui, Miao; Niu, Xuefeng; He, Shihua; Wang, Ruoke; Feng, Yupeng; Kroeker, Andrea; Zuo, Yanan; Wang, Hua; Wang, Ying; Li, Jiade; Li, Chufang; Shi, Yi; Shi, Xuanling; Gao, George F.; Xiang, Ye; Qiu, Xiangguo; Chen, Ling; Zhang, Linqi

    2016-01-01

    Ebola virus infections cause a deadly hemorrhagic disease for which no vaccines or therapeutics has received regulatory approval. Here we show isolation of three (Q206, Q314 and Q411) neutralizing monoclonal antibodies (mAbs) against the surface glycoprotein (GP) of Ebola virus identified in West Africa in 2014 through sequential immunization of Chinese rhesus macaques and antigen-specific single B cell sorting. These mAbs demonstrated potent neutralizing activities against both pseudo and live Ebola virus independent of complement. Biochemical, single particle EM, and mutagenesis analysis suggested Q206 and Q411 recognized novel epitopes in the head while Q314 targeted the glycan cap in the GP1 subunit. Q206 and Q411 appeared to influence GP binding to its receptor NPC1. Treatment with these mAbs provided partial but significant protection against disease in a mouse model of Ebola virus infection. These novel mAbs could serve as promising candidates for prophylactic and therapeutic interventions against Ebola virus infection. PMID:27181584

  7. Shedding of Hepatitis C Virus in Semen of Human Immunodeficiency Virus-Infected Men

    PubMed Central

    Turner, Samuel S.; Gianella, Sara; Yip, Marcus J-S.; van Seggelen, Wouter O.; Gillies, Robert D.; Foster, Andrew L.; Barbati, Zachary R.; Smith, Davey M.; Fierer, Daniel S.

    2016-01-01

    Background. The epidemic of sexually transmitted hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) has been documented for over a decade. Despite this, there is no consensus as to the risk factors for sexual acquisition of HCV in these men. Methods. We obtained paired semen and blood samples at 2-week intervals from HIV-infected MSM with recent and chronic HCV infection and quantified HCV in semen. Results. Hepatitis C virus was quantified in 59 semen specimens from 33 men. Hepatitis C virus was shed in 16 (27%) of semen specimens from 11 (33%) of the men. Median HCV viral load (VL) in semen was 1.49 log10 IU/mL. Hepatitis C virus VL in blood was significantly higher at the time of HCV shedding in semen than when HCV shedding in semen was not detected (P = .002). Furthermore, there was a significant correlation between the HCV VL in blood and semen overall (rs = 0.41; P = .001), and in the subgroup with recent HCV infection (rs = 0.37; P = .02), but not in the subgroup with chronic HCV infection (rs = 0.34; P = .1). Conclusions. One third of HIV-infected MSM coinfected with HCV shed HCV into their semen. Based on the HCV VL in semen in this study, an average ejaculate would deliver up to 6630 IU of virus into the rectum of the receptive partner. Therefore, our data strongly support that condoms should be used during anal intercourse among MSM to prevent transmission of HCV. PMID:27186582

  8. Spatial analysis of feline immunodeficiency virus infection in cougars.

    PubMed

    Wheeler, David C; Waller, Lance A; Biek, Roman

    2010-07-01

    The cougar (Puma concolor) is a large predatory feline found widely in the Americas that is susceptible to feline immunodeficiency virus (FIV), a fast-evolving lentivirus found in wild feline species that is analogous to simian immunodeficiency viruses in wild primates and belongs to the same family of viruses as human immunodeficiency virus. FIV infection in cougars can lead to a weakened immune system that creates opportunities for other infecting agents. FIV prevalence and lineages have been studied previously in several areas in the western United States, but typically without spatially explicit statistical techniques. To describe the distribution of FIV in a sample of cougars located in the northern Rocky Mountain region of North America, we first used kernel density ratio estimation to map the log relative risk of FIV. The risk surface showed a significant cluster of FIV in northwestern Montana. We also used Bayesian cluster models for genetic data to investigate the spatial structure of the feline immunodeficiency virus with virus genetic sequence data. A result of the models was two spatially distinct FIV lineages that aligned considerably with an interstate highway in Montana. Our results suggest that the use of spatial information and models adds novel insight when investigating an infectious animal disease. The results also suggest that the influence of landscape features likely plays an important role in the spatiotemporal spread of an infectious disease within wildlife populations.

  9. Infection of brain-derived cells with the human immunodeficiency virus.

    PubMed Central

    Chiodi, F; Fuerstenberg, S; Gidlund, M; Asjö, B; Fenyö, E M

    1987-01-01

    A malignant glioma cell line was infected with the human T-lymphotropic virus type IIIB isolate of the human immunodeficiency virus. Infection appeared to be latent rather than productive. Through contact with monocytic or lymphoid cells, the virus present in the glioma cells could be transmitted and gave rise to a fully productive infection. Images PMID:3644020

  10. Evidence of Apis cerana Sacbrood virus Infection in Apis mellifera

    PubMed Central

    Gong, Hong-Ri; Chen, Xiu-Xian; Chen, Yan Ping; Hu, Fu-Liang; Zhang, Jiang-Lin; Lin, Zhe-Guang; Yu, Ji-Wei

    2016-01-01

    Sacbrood virus (SBV) is one of the most destructive viruses in the Asian honeybee Apis cerana but is much less destructive in Apis mellifera. In previous studies, SBV isolates infecting A. cerana (AcSBV) and SBV isolates infecting A. mellifera (AmSBV) were identified as different serotypes, suggesting a species barrier in SBV infection. In order to investigate this species isolation, we examined the presence of SBV infection in 318 A. mellifera colonies and 64 A. cerana colonies, and we identified the genotypes of SBV isolates. We also performed artificial infection experiments under both laboratory and field conditions. The results showed that 38 A. mellifera colonies and 37 A. cerana colonies were positive for SBV infection. Phylogenetic analysis based on RNA-dependent RNA polymerase (RdRp) gene sequences indicated that A. cerana isolates and most A. mellifera isolates formed two distinct clades but two strains isolated from A. mellifera were clustered with the A. cerana isolates. In the artificial-infection experiments, AcSBV negative-strand RNA could be detected in both adult bees and larvae of A. mellifera, although there were no obvious signs of the disease, demonstrating the replication of AcSBV in A. mellifera. Our results suggest that AcSBV is able to infect A. mellifera colonies with low prevalence (0.63% in this study) and pathogenicity. This work will help explain the different susceptibilities of A. cerana and A. mellifera to sacbrood disease and is potentially useful for guiding beekeeping practices. PMID:26801569

  11. Host DNA damage response facilitates African swine fever virus infection.

    PubMed

    Simões, Margarida; Martins, Carlos; Ferreira, Fernando

    2013-07-26

    Studies with different viral infection models on virus interactions with the host cell nucleus have opened new perspectives on our understanding of the molecular basis of these interactions in African swine fever virus (ASFV) infection. The present study aims to characterize the host DNA damage response (DDR) occurring upon in vitro infection with the ASFV-Ba71V isolate. We evaluated protein levels during ASFV time-course infection, of several signalling cascade factors belonging to DDR pathways involved in double strand break repair - Ataxia Telangiectasia Mutated (ATM), ATM-Rad 3 related (ATR) and DNA dependent protein kinase catalytic subunit (DNA-PKcs). DDR inhibitory trials using caffeine and wortmannin and ATR inducible-expression cell lines were used to confirm specific pathway activation during viral infection. Our results show that ASFV specifically elicits ATR-mediated pathway activation from the early phase of infection with increased levels of H2AX, RPA32, p53, ATR and Chk1 phosphorylated forms. Viral p72 synthesis was abrogated by ATR kinase inhibitors and also in ATR-kd cells. Furthermore, a reduction of viral progeny was identified in these cells when compared to the outcome of infection in ATR-wt. Overall, our results strongly suggest that the ATR pathway plays an essential role for successful ASFV infection of host cells.

  12. Epidemiology and natural history of hepatitis C virus infection

    PubMed Central

    Lee, Mei-Hsuan; Yang, Hwai-I; Yuan, Yong; L’Italien, Gilbert; Chen, Chien-Jen

    2014-01-01

    Hepatitis C virus (HCV) affects 130-210 million people worldwide and is one of the major risk factors for hepatocellular carcinoma. Globally, at least one third of hepatocellular carcinoma cases are attributed to HCV infection, and 350000 people died from HCV related diseases per year. There is a great geographical variation of HCV infection globally, with risk factors for the HCV infection differing in various countries. The progression of chronic hepatitis C to end-stage liver disease also varies in different study populations. A long-term follow-up cohort enrolling participants with asymptomatic HCV infection is essential for elucidating the natural history of HCV-caused hepatocellular carcinoma, and for exploring potential seromarkers that have high predictability for risk of hepatocellular carcinoma. However, prospective cohorts comprising individuals with HCV infection are still uncommon. The risk evaluation of viral load elevation and associated liver disease/cancer in HCV (REVEAL-HCV) study has followed a cohort of 1095 residents seropositive for antibodies against hepatitis C virus living in seven townships in Taiwan for more than fifteen years. Most of them have acquired HCV infection through iatrogenic transmission routes. As the participants in the REVEAL-HCV study rarely receive antiviral therapies, it provides a unique opportunity to study the natural history of chronic HCV infection. In this review, the prevalence, risk factors and natural history of HCV infection are comprehensively reviewed. The study cohort, data collection, and findings on liver disease progression of the REVEAL-HCV study are described. PMID:25071320

  13. Inhibition of Mayaro virus infection by bovine lactoferrin.

    PubMed

    Carvalho, Carlos A M; Sousa, Ivanildo P; Silva, Jerson L; Oliveira, Andréa C; Gonçalves, Rafael B; Gomes, Andre M O

    2014-03-01

    Mayaro virus (MAYV) is an arbovirus linked to several sporadic outbreaks of a highly debilitating febrile illness in many regions of South America. MAYV is on the verge of urbanization from the Amazon region and no effective antiviral intervention is available against human infections. Our aim was to investigate whether bovine lactoferrin (bLf), an iron-binding glycoprotein, could hinder MAYV infection. We show that bLf promotes a strong inhibition of virus infection with no cytotoxic effects. Monitoring the effect of bLf on different stages of infection, we observed that virus entry into the cell is the heavily compromised event. Moreover, we found that binding of bLf to the cell is highly dependent on the sulfation of glycosaminoglycans, suggesting that bLf impairs virus entry by blocking these molecules. Our findings highlight the antiviral potential of bLf and reveal an effective strategy against one of the major emerging human pathogens in the neotropics.

  14. Hepatitis E Virus Infection in Solid Organ Transplant Recipients, France

    PubMed Central

    Lhomme, Sebastien; Bardiaux, Laurent; Abravanel, Florence; Gallian, Pierre; Kamar, Nassim

    2017-01-01

    The rate of transfusion-transmitted hepatitis E virus (HEV) in transplant recipients is unknown. We identified 60 HEV-positive solid organ transplant patients and retrospectively assessed their blood transfusions for HEV. Seven of 60 patients received transfusions; 3 received HEV-positive blood products. Transfusion is not the major route of infection in this population. PMID:28098552

  15. Physiological effects of Squash vein yellowing virus infection on watermelon

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Squash vein yellowing virus (SqVYV) is the cause of viral watermelon vine decline. In this study, watermelon plants of different ages were inoculated with SqVYV to characterize the physiological response to infection and provide new insights into watermelon vine decline. Physiological responses to...

  16. Antibody-Dependent Enhancement of Marburg Virus Infection

    PubMed Central

    Nakayama, Eri; Tomabechi, Daisuke; Matsuno, Keita; Kishida, Noriko; Yoshida, Reiko; Feldmann, Heinz

    2011-01-01

    Background. Marburg virus (MARV) and Ebola virus (EBOV) cause severe hemorrhagic fever in primates. Earlier studies demonstrated that antibodies to particular epitopes on the glycoprotein (GP) of EBOV enhanced virus infectivity in vitro. Methods. To investigate this antibody-dependent enhancement (ADE) in MARV infection, we produced mouse antisera and monoclonal antibodies (mAbs) to the GPs of MARV strains Angola and Musoke. Results. The infectivity of vesicular stomatitis virus pseudotyped with Angola GP in K562 cells was significantly enhanced in the presence of Angola GP antisera, whereas only minimal ADE activity was seen with Musoke GP antisera. This difference correlated with the percentage of hybridoma clones producing infectivity-enhancing mAbs. Using mAbs to MARV GP, we identified 3 distinct ADE epitopes in the mucinlike region on Angola GP. Interestingly, some of these antibodies bound to both Angola and Musoke GPs but showed significantly higher ADE activity for strain Angola. ADE activity depended on epitopes in the mucinlike region and glycine at amino acid position 547, present in the Angola but absent in the Musoke GP. Conclusions. These results suggest a possible link between ADE and MARV pathogenicity and provide new insights into the mechanisms underlying ADE entry of filoviruses. PMID:21987779

  17. Descending Mediastinitis in Epstein-Barr Virus Infection

    PubMed Central

    van Driel, E. M.; Janssen, M. J. F. M.

    2015-01-01

    Our case report describes a previously healthy 34-year-old male who develops a descending mediastinitis as a complication of an Epstein-Barr virus (EBV) infection. The mediastinitis was suspected to have developed by a breakthrough of a peritonsillar abscess through the space between the alar and prevertebral space. PMID:25740774

  18. Protective effect of dietary xylitol on influenza A virus infection.

    PubMed

    Yin, Sun Young; Kim, Hyoung Jin; Kim, Hong-Jin

    2014-01-01

    Xylitol has been used as a substitute for sugar to prevent cavity-causing bacteria, and most studies have focused on its benefits in dental care. Meanwhile, the constituents of red ginseng (RG) are known to be effective in ameliorating the symptoms of influenza virus infection when they are administered orally for 14 days. In this study, we investigated the effect of dietary xylitol on influenza A virus infection (H1N1). We designed regimens containing various fractions of RG (RGs: whole extract, water soluble fraction, saponin and polysaccharide) and xylitol, and combination of xylitol with the RG fractions. Mice received the various combinations orally for 5 days prior to lethal influenza A virus infection. Almost all the mice died post challenge when xylitol or RGs were administered separately. Survival was markedly enhanced when xylitol was administered along with RGs, pointing to a synergistic effect. The effect of xylitol plus RG fractions increased with increasing dose of xylitol. Moreover, dietary xylitol along with the RG water soluble fraction significantly reduced lung virus titers after infection. Therefore, we suggest that dietary xylitol is effective in ameliorating influenza-induced symptoms when it is administered with RG fractions, and this protective effect of xylitol should be considered in relation to other diseases.

  19. Protective Effect of Dietary Xylitol on Influenza A Virus Infection

    PubMed Central

    Yin, Sun Young; Kim, Hyoung Jin; Kim, Hong-Jin

    2014-01-01

    Xylitol has been used as a substitute for sugar to prevent cavity-causing bacteria, and most studies have focused on its benefits in dental care. Meanwhile, the constituents of red ginseng (RG) are known to be effective in ameliorating the symptoms of influenza virus infection when they are administered orally for 14 days. In this study, we investigated the effect of dietary xylitol on influenza A virus infection (H1N1). We designed regimens containing various fractions of RG (RGs: whole extract, water soluble fraction, saponin and polysaccharide) and xylitol, and combination of xylitol with the RG fractions. Mice received the various combinations orally for 5 days prior to lethal influenza A virus infection. Almost all the mice died post challenge when xylitol or RGs were administered separately. Survival was markedly enhanced when xylitol was administered along with RGs, pointing to a synergistic effect. The effect of xylitol plus RG fractions increased with increasing dose of xylitol. Moreover, dietary xylitol along with the RG water soluble fraction significantly reduced lung virus titers after infection. Therefore, we suggest that dietary xylitol is effective in ameliorating influenza-induced symptoms when it is administered with RG fractions, and this protective effect of xylitol should be considered in relation to other diseases. PMID:24392148

  20. The mortality of neonatal herpes simplex virus infection.

    PubMed

    Lopez-Medina, Eduardo; Cantey, Joseph B; Sánchez, Pablo J

    2015-06-01

    This retrospective study characterized the clinical course of 13 neonates who died with herpes simplex virus infection from 2001 to 2011, representing a 26% case-fatality rate. Fatal disease developed at ≤ 48 hours of age in one-third of infants, was mostly disseminated disease, and occurred despite early administration of high-dose acyclovir therapy.

  1. Evidence of Apeu Virus Infection in Wild Monkeys, Brazilian Amazon.

    PubMed

    Oliveira, Danilo B; Luiz, Ana Paula Moreira Franco; Fagundes, Alexandre; Pinto, Carla Amaral; Bonjardim, Cláudio A; Trindade, Giliane S; Kroon, Erna G; Abrahão, Jônatas S; Ferreira, Paulo C P

    2016-03-01

    Orthobunyaviruses are arboviruses in which at least 30 members are human pathogens. The members of group C orthobunyaviruses were first isolated in the Brazilian Amazon in 1950, since that time little information is accumulated about ecology and the medical impact of these virus groups in Brazil. Herein, we describe the evidence of Apeu virus (APEUV; an Orthobunyavirus member) infection in wild monkeys from the Brazilian Amazon forest. APEUV was detected by using a neutralizing antibody in serum and its RNA, suggesting past and acute infection of Amazonian monkeys by this virus. These results altogether represent an important contribution of orthobunyavirus ecology in the Amazon and an update about recent circulation and risk for humans with expansion of the cities to Amazon forest.

  2. Evidence of Apeu Virus Infection in Wild Monkeys, Brazilian Amazon

    PubMed Central

    Oliveira, Danilo B.; Luiz, Ana Paula Moreira Franco; Fagundes, Alexandre; Pinto, Carla Amaral; Bonjardim, Cláudio A.; Trindade, Giliane S.; Kroon, Erna G.; Abrahão, Jônatas S.; Ferreira, Paulo C. P.

    2016-01-01

    Orthobunyaviruses are arboviruses in which at least 30 members are human pathogens. The members of group C orthobunyaviruses were first isolated in the Brazilian Amazon in 1950, since that time little information is accumulated about ecology and the medical impact of these virus groups in Brazil. Herein, we describe the evidence of Apeu virus (APEUV; an Orthobunyavirus member) infection in wild monkeys from the Brazilian Amazon forest. APEUV was detected by using a neutralizing antibody in serum and its RNA, suggesting past and acute infection of Amazonian monkeys by this virus. These results altogether represent an important contribution of orthobunyavirus ecology in the Amazon and an update about recent circulation and risk for humans with expansion of the cities to Amazon forest. PMID:26787153

  3. Zika Virus Infection and Microcephaly: Evidence for a Causal Link

    PubMed Central

    Wang, Jin-Na; Ling, Feng

    2016-01-01

    Zika virus (ZIKV) is a flavivirus related to the Dengue, yellow fever and West Nile viruses. Since the explosive outbreaks of ZIKV in Latin America in 2015, a sudden increase in the number of microcephaly cases has been observed in infants of women who were pregnant when they contracted the virus. The severity of this condition raises grave concerns, and extensive studies on the possible link between ZIKV infection and microcephaly have been conducted. There is substantial evidence suggesting that there is a causal link between ZIKV and microcephaly, however, future studies are warranted to solidify this association. To summarize the most recent evidence on this issue and provide perspectives for future studies, we reviewed the literature to identify existing evidence of the causal link between ZIKV infection and microcephaly within research related to the epidemics, laboratory diagnosis, and possible mechanisms. PMID:27775637

  4. Zika Virus Infection and Microcephaly: Evidence for a Causal Link.

    PubMed

    Wang, Jin-Na; Ling, Feng

    2016-10-20

    Zika virus (ZIKV) is a flavivirus related to the Dengue, yellow fever and West Nile viruses. Since the explosive outbreaks of ZIKV in Latin America in 2015, a sudden increase in the number of microcephaly cases has been observed in infants of women who were pregnant when they contracted the virus. The severity of this condition raises grave concerns, and extensive studies on the possible link between ZIKV infection and microcephaly have been conducted. There is substantial evidence suggesting that there is a causal link between ZIKV and microcephaly, however, future studies are warranted to solidify this association. To summarize the most recent evidence on this issue and provide perspectives for future studies, we reviewed the literature to identify existing evidence of the causal link between ZIKV infection and microcephaly within research related to the epidemics, laboratory diagnosis, and possible mechanisms.

  5. Clinical significance of occult hepatitis B virus infection.

    PubMed

    Romero, Miriam; Madejón, Antonio; Fernández-Rodríguez, Conrado; García-Samaniego, Javier

    2011-03-28

    Occult hepatitis B virus (HBV) infection (OBI) is defined as the presence of HBV DNA in the liver (with or without detectable HBV DNA in serum) for individuals testing HBV surface antigen negative. Until recently, the clinical effect of OBI was unclear on the progression of liver disease; on the development of hepatocellular carcinoma; and on the risk for reactivation or transmission of HBV infection. Several studies suggest a high prevalence of OBI among patients with cryptogenic chronic liver disease, but its role in the progression to cirrhosis remains unclear. Although OBI has been well documented in human immunodeficiency virus (HIV)-positive patients, especially among those coinfected with hepatitis C virus, further studies are needed to determine its current clinical impact in HIV setting.

  6. The Variegate Neurological Manifestations of Varicella Zoster Virus Infection

    PubMed Central

    Nagel, Maria A.; Cohrs, Randall J.; Mahalingam, Ravi

    2014-01-01

    Varicella zoster virus (VZV) is an exclusively human neurotropic alphaherpesvirus. Primary infection causes varicella (chickenpox), after which the virus becomes latent in ganglionic neurons along the entire neuraxis. With advancing age or immunosuppression, cell-mediated immunity to VZV declines, and the virus reactivates to cause zoster (shingles), dermatomal distribution, pain, and rash. Zoster is often followed by chronic pain (postherpetic neuralgia), cranial nerve palsies, zoster paresis, vasculopathy, meningoencephalitis, and multiple ocular disorders. This review covers clinical, laboratory, and pathological features of neurological complications of VZV reactivation, including diagnostic testing to verify active VZV infection in the nervous system. Additional perspectives are provided by discussions of VZV latency, animal models to study varicella pathogenesis and immunity, and of the value of vaccination of elderly individuals to boost cell-mediated immunity to VZV and prevent VZV reactivation. PMID:23884722

  7. Hepatitis virus C infection, adipokines and hepatic steato-fibrosis.

    PubMed

    Ciurtin, Coziana; Stoica, Victor

    2008-01-01

    Hepatitis C viral infection is accompanied by various serum alterations that could explain its molecular impact on hepatic structure and metabolic homeostasis. Recently it has been shown that adipocytokines play a pivotal role in development of hepatic steato-fibrosis, different studies giving a support of the hypothesis that the balance of adipocytokine expression is a key regulator for the progression of hepatic steatosis and fibrosis. The association between insulin resistance and hepatitis C virus genotypes and liver fibrosis stage foreshadowed that virus-induced insulin resistance may be a mechanism for fibrogenesis in chronic hepatitis C virus infection. The main importance of adipocytokine profile detection consists in the prediction of steatosis induction that has clinical relevance, being associated with advanced fibrosis and hyporesponsiveness to antiviral therapy.

  8. Current Approaches for Diagnosis of Influenza Virus Infections in Humans

    PubMed Central

    Vemula, Sai Vikram; Zhao, Jiangqin; Liu, Jikun; Wang, Xue; Biswas, Santanu; Hewlett, Indira

    2016-01-01

    Despite significant advancement in vaccine and virus research, influenza continues to be a major public health concern. Each year in the United States of America, influenza viruses are responsible for seasonal epidemics resulting in over 200,000 hospitalizations and 30,000–50,000 deaths. Accurate and early diagnosis of influenza viral infections are critical for rapid initiation of antiviral therapy to reduce influenza related morbidity and mortality both during seasonal epidemics and pandemics. Several different approaches are currently available for diagnosis of influenza infections in humans. These include viral isolation in cell culture, immunofluorescence assays, nucleic acid amplification tests, immunochromatography-based rapid diagnostic tests, etc. Newer diagnostic approaches are being developed to overcome the limitations associated with some of the conventional detection methods. This review discusses diagnostic approaches currently available for detection of influenza viruses in humans. PMID:27077877

  9. A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection.

    PubMed

    Akahata, Wataru; Yang, Zhi-Yong; Andersen, Hanne; Sun, Siyang; Holdaway, Heather A; Kong, Wing-Pui; Lewis, Mark G; Higgs, Stephen; Rossmann, Michael G; Rao, Srinivas; Nabel, Gary J

    2010-03-01

    Chikungunya virus (CHIKV) has infected millions of people in Africa, Europe and Asia since this alphavirus reemerged from Kenya in 2004. The severity of the disease and the spread of this epidemic virus present a serious public health threat in the absence of vaccines or antiviral therapies. Here, we describe a new vaccine that protects against CHIKV infection of nonhuman primates. We show that selective expression of viral structural proteins gives rise to virus-like particles (VLPs) in vitro that resemble replication-competent alphaviruses. Immunization with these VLPs elicited neutralizing antibodies against envelope proteins from alternative CHIKV strains. Monkeys immunized with VLPs produced high-titer neutralizing antibodies that protected against viremia after high-dose challenge. We transferred these antibodies into immunodeficient mice, where they protected against subsequent lethal CHIKV challenge, indicating a humoral mechanism of protection. Immunization with alphavirus VLP vaccines represents a strategy to contain the spread of CHIKV and related pathogenic viruses in humans.

  10. Influenza A virus infections in marine mammals and terrestrial carnivores.

    PubMed

    Harder, Timm C; Siebert, Ursula; Wohlsein, Peter; Vahlenkamp, Thomas

    2013-01-01

    Influenza A viruses (IAV), members of the Orthomyxoviridae, cover a wide host spectrum comprising a plethora of avian and, in comparison, a few mammalian species. The viral reservoir and gene pool are kept in metapopulations of aquatic wild birds. The mammalian-adapted IAVs originally arose by transspecies transmission from avian sources. In swine, horse and man, species-adapted IAV lineages circulate independently of the avian reservoir and cause predominantly respiratory disease of highly variable severity. Sporadic outbreaks of IAV infections associated with pneumonic clinical signs have repeatedly occurred in marine mammals (harbour seals [Phoca vitulina]) off the New England coast of the U.S.A. due to episodic transmission of avian IAV. However, no indigenous marine mammal IAV lineages are described. In contrast to marine mammals, avian- and equine-derived IAVs have formed stable circulating lineages in terrestrial carnivores: IAVs of subtype H3N2 and H3N8 are found in canine populations in South Korea, China, and the U.S.A. Experimental infections revealed that dogs and cats can be infected with an even wider range of avian IAVs. Cats, in particular, also proved susceptible to native infection with human pandemic H1N1 viruses and, according to serological data, may be vulnerable to infection with further human-adapted IAVs. Ferrets are susceptible to a variety of avian and mammalian IAVs and are an established animal model of human IAV infection. Thus, a potential role of pet cats, dogs and ferrets as mediators of avian-derived viruses to the human population does exist. A closer observation for influenza virus infections and transmissions at this animal-human interface is indicated.

  11. Human Ebola virus infection results in substantial immune activation.

    PubMed

    McElroy, Anita K; Akondy, Rama S; Davis, Carl W; Ellebedy, Ali H; Mehta, Aneesh K; Kraft, Colleen S; Lyon, G Marshall; Ribner, Bruce S; Varkey, Jay; Sidney, John; Sette, Alessandro; Campbell, Shelley; Ströher, Ute; Damon, Inger; Nichol, Stuart T; Spiropoulou, Christina F; Ahmed, Rafi

    2015-04-14

    Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10-50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1-2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients' discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus.

  12. Torque teno virus (TTV) infection in sows and suckling piglets.

    PubMed

    Sibila, M; Martínez-Guinó, L; Huerta, E; Mora, M; Grau-Roma, L; Kekarainen, T; Segalés, J

    2009-06-12

    Torque teno virus (TTV) is a single-stranded DNA virus that has been detected in serum of primate and non-primate species including swine. Little information on swine TTV infection and transmission dynamics is nowadays available. The goal of this study was to gain insight into the potential role of the sow in transmitting TTV to piglets and the infection dynamics of both swine TTV genogroups (TTV1 and TTV2) during the lactation period. Serum samples from 44 sows at 1-week post-farrowing and 215 piglets at 1 and 3 weeks of age were tested using TTV1 and TTV2 PCR methods. Sow parity distribution and the number of delivered piglets (liveborn, stillborn and mummified) per each studied sow were recorded. TTV1 was detected in higher percentages than TTV2 in both sows (75% vs. 43%, respectively) and piglets at 1 (17% vs. 7%, respectively) and 3 (32% vs. 12%, respectively) weeks of age. TTV1 and TTV2 co-infections were observed in higher percentages in sows (34%) than in piglets (2% and 4% at 1 and 3 weeks of age, respectively). Detection of swine TTV genogroups in sows was not associated with their detection in piglets. Moreover, there were piglets infected at 1 week of age with a swine TTV genogroup different from the one detected in their dam. The number of sows delivering stillborns and the mean number of stillborns per sow tended to be higher in the TTV2 infected sows; this value was significantly higher when co-infected sows (TTV1 and TTV2) were compared with non-co-infected ones. Old parity sows had a higher percentage of TTV1 infected 1-week-old piglets. Results of the present study showed that the TTV infection occurs early in the production system and that these viruses may be transmitted from sow-to-piglet but also from piglet-to-piglet in farrowing facilities.

  13. Emerging, novel, and known influenza virus infections in humans.

    PubMed

    Tang, Julian W; Shetty, Nandini; Lam, Tommy T Y; Hon, K L Ellis

    2010-09-01

    Influenza viruses continue to cause yearly epidemics and occasional pandemics in humans. In recent years, the threat of a possible influenza pandemic arising from the avian influenza A(H5N1) virus has prompted the development of comprehensive pandemic preparedness programs in many countries. The recent emergence of the pandemic influenza A(H1N1) 2009 virus from the Americas in early 2009, although surprising in its geographic and zoonotic origins, has tested these preparedness programs and revealed areas in which further work is necessary. Nevertheless, the plethora of epidemiologic, diagnostic, mathematical and phylogenetic modeling, and investigative methodologies developed since the severe acute respiratory syndrome outbreak of 2003 and the subsequent sporadic human cases of avian influenza have been applied effectively and rapidly to the emergence of this novel pandemic virus. This article summarizes some of the findings from such investigations, including recommendations for the management of patients infected with this newly emerged pathogen.

  14. Neurologic Complications of Influenza B Virus Infection in Adults, Romania

    PubMed Central

    Florescu, Simin A.; Lupulescu, Emilia; Zaharia, Mihaela; Tardei, Gratiela; Lazar, Mihaela; Ceausu, Emanoil; Ruta, Simona M.

    2017-01-01

    We characterized influenza B virus–related neurologic manifestations in an unusually high number of hospitalized adults at a tertiary care facility in Romania during the 2014–15 influenza epidemic season. Of 32 patients with a confirmed laboratory diagnosis of influenza B virus infection, neurologic complications developed in 7 adults (median age 31 years). These complications were clinically diagnosed as confirmed encephalitis (4 patients), possible encephalitis (2 patients), and cerebellar ataxia (1 patient). Two of the patients died. Virus sequencing identified influenza virus B (Yam)-lineage clade 3, which is representative of the B/Phuket/3073/2013 strain, in 4 patients. None of the patients had been vaccinated against influenza. These results suggest that influenza B virus can cause a severe clinical course and should be considered as an etiologic factor for encephalitis. PMID:28322689

  15. Antiviral Activity of HPMPC (Cidofovir) Against ORF Virus Infected Lambs

    PubMed Central

    Scagliarini, A.; McInnes, C.J.; Gallina, L.; Dal, Pozzo F.; Scagliarini, L.; Snoeck, R.; Prosperi, S.; Sales, J.; Gilray, J.A.; Nettleton, P.F.

    2007-01-01

    (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]-2,6-diaminopurine (HPMPC, cidofovir, CDV, Vistide®) is an acyclic nucleoside analogue with a potent and selective activity against a broad spectrum of DNA viruses including the poxviruses. In this study we present the results of different treatment regimens in lambs experimentally infected with orf virus with different cidofovir formulations prepared in Beeler basis and Unguentum M. Our results show that choice of excipient, concentration of cidofovir and treatment regimen were all important to the clinical outcome of the therapy. Whilst one particular regimen appeared to exacerbate the lesion, treatment with 1% w/v cidofovir cream, prepared in Beeler Basis, for 4 consecutive days did result in milder lesions that resolved more quickly than untreated lesions. Furthermore the scabs of the treated animals contained significantly lower amounts of viable virus meaning there should be less contamination of the environment with virus than would normally occur. PMID:17049627

  16. Cryo-Electron Microscopy of Viruses Infecting Bacterium

    NASA Astrophysics Data System (ADS)

    Chiu, Wah

    2010-03-01

    Single particle cryo-EM can yield structures of infectious bacterial viruses with and without imposed icosahedral symmetry at subnanometer resolution. Reconstructions of infectious and empty phage particles show substantial differences in the portal vertex protein complex at one of the 12 pentameric vertices in the icosahedral virus particle through which the viral genomes are packaged or released. In addition, electron cryo-tomography of viruses during infecting its bacterial host cell displayed multiple conformations of the tail fiber of the virus. Our structural observations by single particle and tomographic reconstructions suggest a mechanism whereby the viral tail fibers, upon binding to the host cell, induce a cascade of structural alterations of the portal vertex protein complex that triggers DNA release.

  17. Experimental infection of nonhuman primates with sandfly fever virus.

    PubMed

    McClain, D J; Summers, P L; Pratt, W D; Davis, K J; Jennings, G B

    1997-05-01

    Due to the lack of an animal model, previous studies of sandfly fever have relied upon human challenge trials. We examined the infectivity and potential pathogenicity of sandfly fever virus in cynomolgus monkeys (Macaca fascicularis). Three different preparations of sandfly fever virus. Sicilian strain, and a placebo were compared by different routes of administration. The most notable postchallenge clinical event was a decrease in lymphocytes in the intramuscularly challenged monkeys. Plaque-reduction neutralization responses peaked earlier in animals challenged intravenously as compared with those in animals challenged intramuscularly. There was no evidence for neurotropism or meningeal inflammation. Sandfly fever virus was infectious for cynomolgus monkeys, but produced no detectable clinical disease that might serve as a marker for animal modeling studies. On the other hand, the preclinical data provide supportive evidence for safe parenteral administration of a Sicilian strain of sandfly fever virus inoculum to humans as a challenge model for sandfly fever disease.

  18. Human immunodeficiency virus and hepatitis C virus/hepatitis B virus co-infection in Southern Brazil: clinical and epidemiological evaluation.

    PubMed

    Raboni, Sonia Mara; Tuon, Felipe Francisco; Beloto, Nayara Carvalho Polido; Demeneck, Henrique; Oliveira, Andre; Largura, Denis; Sagrado, Andressa Gervasoni; Lima, Bárbara Perdonsini; Franzoni, João Paulo; Pedroso, Maria Lucia

    2014-01-01

    Hepatitis B virus, hepatitis C virus and human immunodeficiency virus share a similar transmission pathway and are often diagnosed in the same patient. These patients tend to have a faster progression of hepatic fibrosis. This cross-sectional study describes the demographic features and clinical profile of human immunodeficiency virus/hepatitis co-infected patients in Paraná, Southern Brazil. A total of 93 human immunodeficiency virus-infected patients attending a tertiary care academic hospital in Southern Brazil were included. Clinical, demographic and epidemiological data were evaluated. Hepatitis B virus and/or hepatitis C virus positive serology was found in 6.6% of patients. The anti-hepatitis C virus serum test was positive in 85% (79/93) of patients, and the infection was confirmed in 72% of the cases. Eighteen patients (19%) were human immunodeficiency virus/hepatitis B virus positive (detectable HBsAg). Among co-infected patients, there was a high frequency of drug use, and investigations for the detection of co-infection were conducted late. A low number of patients were eligible for treatment and, although the response to antiretroviral therapy was good, there was a very poor response to hepatitis therapy. Our preliminary findings indicate the need for protocols aimed at systematic investigation of hepatitis B virus and hepatitis C virus in human immunodeficiency virus-infected patients, thus allowing for early detection and treatment of co-infected patients.

  19. A conservation law for virus infection kinetics in vitro.

    PubMed

    Kakizoe, Yusuke; Morita, Satoru; Nakaoka, Shinji; Takeuchi, Yasuhiro; Sato, Kei; Miura, Tomoyuki; Beauchemin, Catherine A A; Iwami, Shingo

    2015-07-07

    Conservation laws are among the most important properties of a physical system, but are not commonplace in biology. We derived a conservation law from the basic model for viral infections which consists in a small set of ordinary differential equations. We challenged the conservation law experimentally for the case of a virus infection in a cell culture. We found that the derived, conserved quantity remained almost constant throughout the infection period, implying that the derived conservation law holds in this biological system. We also suggest a potential use for the conservation law in evaluating the accuracy of experimental measurements.

  20. Human papilloma virus (HPV) infection in children and adolescents.

    PubMed

    Mammas, Ioannis N; Sourvinos, George; Spandidos, Demetrios A

    2009-03-01

    Human papilloma viruses (HPV) are common pathogens associated with a wide range of cutaneous and mucosal infections in childhood. Different HPV types can cause common warts, genital warts, low-grade as well as high-grade squamous intraepithelial lesions. Anogenital warts represent an issue with legal and clinical implications and evaluation of children for the possibility of sexual abuse should be considered in all cases. Recurrent respiratory papillomatosis has also been associated with HPV infection in a variety of studies. The recently introduced HPV vaccination is expected to prevent HPV-related cervical cancer in adulthood; however, HPV infection will continue to affect children.

  1. UNA virus: first report of human infection in Argentina.

    PubMed

    Diaz, Luis Adrián; Spinsanti, Lorena Ivana; Almiron, Walter Ricardo; Contigiani, Marta Silvia

    2003-01-01

    Una virus (UNAV), Togaviridae family, is widely distributed in South America, where infections have been detected in mosquitoes and vertebrate hosts (humans, birds and horses). We analyzed human sera from Córdoba inhabitants aged 44 to 89 years and using a neutralization test, we found a prevalence of UNAV antibodies of 3.8% (3/79). The low titers detected suggest past infections probably acquired in rural areas of the Province of Córdoba (central Argentina). None sera were found positive for MAYV neutralizing antibodies. This is the first report of human infections by UNAV in Argentina.

  2. THE INFECTION OF FERRETS WITH SWINE INFLUENZA VIRUS

    PubMed Central

    Shope, Richard E.

    1934-01-01

    The experiments described confirm the earlier observation of Smith, Andrewes, and Laidlaw that the swine influenza virus is pathogenic for ferrets when administered intranasally. A disease that is clinically more severe and pathologically more extensive than that described by the above workers is obtained if inoculation with the virus is performed under ether anesthesia. Animals infected in this way show at autopsy an edematous type of pneumonia of lobar distribution which may terminate fatally. The virus maintains its pathogenicity for ferrets when stored in 50 per cent glycerol at refrigerator temperature for as long as 75 days. After serial passage through 16 ferrets the virus is still capable of inducing swine influenza when mixed with H. influenzae suis and administered intranasally to swine. Ferret passage causes no apparent attenuation of the virus for swine. Serum from pigs recovered from swine influenza is capable of neutralizing the ferret-passaged virus for either swine or ferrets. Likewise serum from recovered ferrets neutralizes the swine influenza virus for either ferrets or swine. PMID:19870285

  3. Early pathogenesis of transmucosal feline immunodeficiency virus infection.

    PubMed

    Obert, Leslie A; Hoover, Edward A

    2002-06-01

    To identify the early target cells and tissues in transmucosal feline immunodeficiency virus (FIV) infection, cats were exposed to a clade C FIV isolate via the oral-nasal or vaginal mucosa and multiple tissues were examined by virus isolation coculture (VI), DNA PCR, catalyzed tyramide signal-amplified in situ hybridization (TSA-ISH), and immunohistochemistry between days 1 and 12 postinoculation (p.i.). FIV RNA was detected in tonsil and oral or vaginal mucosa as early as 1 day p.i. by TSA-ISH and in retropharyngeal, tracheobronchial, or external iliac lymph nodes and sometimes in spleen or blood mononuclear cells by day 2, indicating that regional and distant spread of virus-infected cells occurred rapidly after mucosal exposure. By day 8, viral RNA, DNA, and culturable virus were uniformly detected in regional and distant tissues, connoting systemic infection. TSA-ISH proved more sensitive than DNA PCR in detecting early FIV-infected cells. In mucosal tissues, the earliest demonstrable FIV-bearing cells were either within or subjacent to the mucosal epithelium or were in germinal centers of regional lymph nodes. The FIV(+) cells were of either of two morphological types, large stellate or small round. Those FIV RNA(+) cells which could be colabeled for a phenotype marker, were labeled for either dendritic-cell-associated protein p55 or T-lymphocyte receptor antigen CD3. These studies indicate that FIV crosses mucous membranes within hours after exposure and rapidly traffics via dendritic and T cells to systemic lymphoid tissues, a pathway similar to that thought to occur in the initial phase of infection by the human and simian immunodeficiency viruses.

  4. Hepatitis B virus and hepatitis C virus infection among HIV-1-infected injection drug users in Dali, China: prevalence and infection status in a cross-sectional study.

    PubMed

    Dong, Yuan; Qiu, Chao; Xia, Xueshan; Wang, Jing; Zhang, Haiyan; Zhang, Xiaoyan; Xu, Jianqing

    2015-04-01

    To assess the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and to investigate their mutual influences on infection status among human immunodeficiency virus type 1 (HIV-1)-seropositive injection drug users (IDUs). A cross-sectional study was conducted among HIV infected IDUs in Dali, China. The participants were tested for serological markers of HBV and HCV infection, alanine transaminase (ALT) activity and CD4(+) T cell count. HCV genotype was determined by sequencing. Of 529 patients, 498 (94.1 %) HIV infected IDUs agreed to participate. The overall prevalence of HCV infection (anti-HCV antibody positive) and spontaneous HCV clearance were 90.8 % (452/498) and 21.5 % (97/452), respectively. Of 411 subjects who had not received HBV vaccine, 296 (72.0 %) were positive for antibody against HBV core antigen (HBcAb), while 274 (66.7 %) were positive for both HCV antibody and HBcAb. HBV antigens were detected in 52 of the HBV-infected subjects (17.6 %). HCV clearance was associated with HBV antigenemia (p = 0.0002) and higher CD4(+) T cell count (p = 0.0294). Resolved HBV infection was associated with HCV genotype 3 (p = 0.0365). HBV and HCV infection are highly prevalent and mutually influence infection status in HIV-1 infected IDUs in Dali, China.

  5. Complex Dynamics of Virus Spread from Low Infection Multiplicities: Implications for the Spread of Oncolytic Viruses

    PubMed Central

    Rodriguez-Brenes, Ignacio A.; Hofacre, Andrew; Fan, Hung; Wodarz, Dominik

    2017-01-01

    While virus growth dynamics have been well-characterized in several infections, data are typically collected once the virus population becomes easily detectable. Earlier dynamics, however, remain less understood. We recently reported unusual early dynamics in an experimental system using adenovirus infection of human embryonic kidney (293) cells. Under identical experimental conditions, inoculation at low infection multiplicities resulted in either robust spread, or in limited spread that eventually stalled, with both outcomes occurring with approximately equal frequencies. The reasons underlying these observations have not been understood. Here, we present further experimental data showing that inhibition of interferon-induced antiviral states in cells results in a significant increase in the percentage of robust infections that are observed, implicating a race between virus replication and the spread of the anti-viral state as a central mechanism. Analysis of a variety of computational models, however, reveals that this alone cannot explain the simultaneous occurrence of both viral growth outcomes under identical conditions, and that additional biological mechanisms have to be invoked to explain the data. One such mechanism is the ability of the virus to overcome the antiviral state through multiple infection of cells. If this is included in the model, two outcomes of viral spread are found to be simultaneously stable, depending on initial conditions. In stochastic versions of such models, the system can go by chance to either state from identical initial conditions, with the relative frequency of the outcomes depending on the strength of the interferon-based anti-viral response, consistent with the experiments. This demonstrates considerable complexity during the early phase of the infection that can influence the ability of a virus to become successfully established. Implications for the initial dynamics of oncolytic virus spread through tumors are discussed

  6. In vivo imaging of cidofovir treatment of cowpox virus infection.

    PubMed

    Goff, Arthur; Twenhafel, Nancy; Garrison, Aura; Mucker, Eric; Lawler, James; Paragas, Jason

    2007-09-01

    Variola virus and other members of the genus Orthopoxviruses constitute a prominent bioterrorism and public health threat. Treatment with the anti-viral drug cidofovir inhibits replication of orthopoxviruses in vitro and in vivo. In this study, we visualized the effect of cidofovir on viral kinetics in orthopoxvirus infected mice by using whole-body fluorescence imaging (FI). We engineered a cowpox virus (CPV) expressing the enhanced green fluorescent protein (GFP). Single-step growth curves and calculated 50% lethal doses (LD(50)) of wild-type CPX (Wt-CPV) and GFP-expressing CPX (GFP-CPV) were comparable. Whole-body FI first detected GFP fluorescence in the mesenteric tissue of untreated animals on post-infection day (PID) 1. On PID 3 GFP signal was detected throughout the mesentery, in all abdominal organs by PID 5 and in most major organs, except for the heart and brain by PID 6. Infected animals treated with 25mg/kg of cidofovir also began showing signs of viral replication on PID 1, however, the fluorescent signal was limited only to discrete foci throughout the course of the infection. This work describes the first use of an established Orthopox model of infection to evaluate drug efficacy and track virus progression on a macroscopic level.

  7. IL-6 ameliorates acute lung injury in influenza virus infection

    PubMed Central

    Yang, Mei-Lin; Wang, Chung-Teng; Yang, Shiu-Ju; Leu, Chia-Hsing; Chen, Shun-Hua; Wu, Chao-Liang; Shiau, Ai-Li

    2017-01-01

    Interleukin 6 (IL-6) is involved in innate and adaptive immune responses to defend against pathogens. It also participates in the process of influenza infection by affecting viral clearance and immune cell responses. However, whether IL-6 impacts lung repair in influenza pathogenesis remains unclear. Here, we studied the role of IL-6 in acute influenza infection in mice. IL-6-deficient mice infected with influenza virus exhibited higher lethality, lost more body weight and had higher fibroblast accumulation and lower extracellular matrix (ECM) turnover in the lung than their wild-type counterparts. Deficiency in IL-6 enhanced proliferation, migration and survival of lung fibroblasts, as well as increased virus-induced apoptosis of lung epithelial cells. IL-6-deficient lung fibroblasts produced elevated levels of TGF-β, which may contribute to their survival. Furthermore, macrophage recruitment to the lung and phagocytic activities of macrophages during influenza infection were reduced in IL-6-deficient mice. Collectively, our results indicate that IL-6 is crucial for lung repair after influenza-induced lung injury through reducing fibroblast accumulation, promoting epithelial cell survival, increasing macrophage recruitment to the lung and enhancing phagocytosis of viruses by macrophages. This study suggests that IL-6 may be exploited for lung repair during influenza infection. PMID:28262742

  8. Co-infection with Influenza Viruses and Influenza-Like Virus During the 2015/2016 Epidemic Season.

    PubMed

    Szymański, Karol; Cieślak, K; Kowalczyk, D; Brydak, L B

    2017-02-09

    Concerning viral infection of the respiratory system, a single virus can cause a variety of clinical symptoms and the same set of symptoms can be caused by different viruses. Moreover, infection is often caused by a combination of viruses acting at the same time. The present study demonstrates, using multiplex RT-PCR and real-time qRT-PCR, that in the 2015/2016 influenza season, co-infections were confirmed in patients aged 1 month to 90 years. We found 73 co-infections involving influenza viruses, 17 involving influenza viruses and influenza-like viruses, and six involving influenza-like viruses. The first type of co-infections above mentioned was the most common, amounting to 51 cases, with type A and B viruses occurring simultaneously. There also were four cases of co-infections with influenza virus A/H1N1/pdm09 and A/H1N1/ subtypes and two cases with A/H1N1/pdm09 and A/H3N2/ subtypes. The 2015/2016 epidemic season was characterized by a higher number of confirmed co-infections compared with the previous seasons. Infections by more than one respiratory virus were most often found in children and in individuals aged over 65.

  9. The cycle of human herpes simplex virus infection: virus transport and immune control.

    PubMed

    Cunningham, Anthony L; Diefenbach, Russell J; Miranda-Saksena, Monica; Bosnjak, Lidija; Kim, Min; Jones, Cheryl; Douglas, Mark W

    2006-09-15

    After infection of skin or mucosa, herpes simplex virus enters the sensory nerve endings and is conveyed by retrograde axonal transport to the dorsal root ganglion, where the virus develops lifelong latency. Intermittent reactivation, which is spontaneous in humans, leads to anterograde transport of virus particles and proteins to the skin or mucosa, where the virus is shed and/or causes disease. Immune control of viral infection and replication occurs at the level of skin or mucosa during initial or recurrent infection and also within the dorsal root ganglion, where immune mechanisms control latency and reactivation. This article examines current views on the mechanisms of retrograde and anterograde transport of the virus in axons and the mechanisms of innate and adaptive immunity that control infection in the skin or mucosa and in the dorsal root ganglion--in particular, the role of interferons, myeloid and plasmacytoid dendritic cells, CD4(+) and CD8(+) T cells, and interferon- gamma and other cytokines, including their significance in the development of vaccines for genital herpes.

  10. Natural Vaccinia Virus Infection: Diagnosis, Isolation, and Characterization.

    PubMed

    Geessien Kroon, Erna; Santos Abrahão, Jônatas; de Souza Trindade, Giliane; Pereira Oliveira, Graziele; Moreira Franco Luiz, Ana Paula; Barbosa Costa, Galileu; Teixeira Lima, Mauricio; Silva Calixto, Rafael; de Oliveira, Danilo Bretas; Drumond, Betânia Paiva

    2016-08-12

    Natural infections of Vaccinia virus (VACV)-the prototype species of the Orthopoxvirus genus, from the family Poxviridae and subfamily Chordopoxvirinae-cause an occupational emergent zoonotic disease that is primarily associated with the handling of infected dairy cattle. In humans, VACV infection is characterized by skin lesions, primarily on the hands, and accompanied by systemic symptoms such as fever, myalgia, headache, and lymphadenopathy. The diagnosis of VACV is usually performed according to the methods described for other orthopoxviruses. This unit describes the methods utilized to obtain clinical samples, the serological and molecular techniques used for diagnosis, and the isolation methods and techniques used for molecular and biological characterization of the viruses. © 2016 by John Wiley & Sons, Inc.

  11. Chromatin dynamics during herpes simplex virus-1 lytic infection.

    PubMed

    Placek, Brandon J; Berger, Shelley L

    2010-01-01

    Herpes simplex virus type 1 is a DNA virus that can establish lytic infections in epithelial cells and latent infections in sensory neurons. Upon entry into the nucleus the genome of HSV-1 rapidly associates with histone proteins. Similar to the genomes of the cellular host, HSV-1 is subject to chromatin-based regulation of transcription and replication. However, unlike the host genome, nucleosomes appear to be underrepresented on the HSV genome. During lytic infection, when the genome is transcribed, the HSV-1 chromatin structure appears to be disorganized, and characterized by histone variant sub-types and post-translational modifications representative of active chromatin. In contrast, during latency, when the majority of the viral genome is transcriptionally silent, the chromatin is compacted into a regularly repeating, compact heterochromatic structure. Here we discuss recent studies that underscore the importance of chromatin regulation during the lytic phase of the HSV-1 life-cycle.

  12. Animal Models of Zika Virus Infection, Pathogenesis, and Immunity.

    PubMed

    Morrison, Thomas E; Diamond, Michael S

    2017-04-15

    Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that now causes epidemics affecting millions of people on multiple continents. The virus has received global attention because of some of its unusual epidemiological and clinical features, including persistent infection in the male reproductive tract and sexual transmission, an ability to cross the placenta during pregnancy and infect the developing fetus to cause congenital malformations, and its association with Guillain-Barré syndrome in adults. This past year has witnessed an intensive effort by the global scientific community to understand the biology of ZIKV and to develop pathogenesis models for the rapid testing of possible countermeasures. Here, we review the recent advances in and utility and limitations of newly developed mouse and nonhuman primate models of ZIKV infection and pathogenesis.

  13. Hepatitis B virus infection and primary hepatocellular carcinoma.

    PubMed Central

    Feitelson, M

    1992-01-01

    For many years, epidemiological studies have demonstrated a strong link between chronic hepatitis B virus (HBV) infection and the development of primary hepatocellular carcinoma (PHC). Other hepatocarcinogens such as hepatitis C virus and aflatoxin also contribute to hepatocarcinogenesis either in conjunction with HBV infection or alone. Cellular and molecular biological studies are providing explanations for the HBV-PHC relationship, and models are now being formulated to further test the relative importance of various factors such as viral DNA integration, activation of oncogenes, genetic instability, loss of tumor suppressor genes, and trans-activating properties of HBV to the pathogenesis of PHC. Further research will probably define more than a single mechanism whereby chronic HBV infection results in PHC. PMID:1323384

  14. Treatment of feline leukemia virus (FeLV) infection.

    PubMed

    Hartmann, K; Block, A; Ferk, G; Beer, B; Vollmar, A; Lutz, H

    1999-09-01

    FeLV infection is still considered to account for most disease-related deaths in pet cats. Different treatment attempts with various drugs were performed in the past but none resulted in healing or complete virus elimination. Therefore, it caused a sensation when Horber and Mayr [Horber, D., Mayr, B., 1991. Prax. 19, 311-314; Horber, D., Schnabl, W., Mayr, B., 1992. Tierarztl. Umschau 47, 556-560; Mayr, B., Horber, D., 1992. Kleintierprax. 37, 515-518] published that they were able to cure 80 to 100% FeLV-infected cats from viremia by using an immunomodulating compound. Articles in cat breeder and cat owner journals appeared assuming that obviously there is a rescue for FeLV-infected cats suffering from this deadly infection. The immunomodulator [Buttner, M., 1993. Comp. Immun. Microbiol. Infect. Dis. 18, 1-10] used in those studies was the so-called 'paramunity inducer' PIND-ORF (Baypamun, Bayer, Leverkusen, Germany) consisting of inactivated parapox ovis virus. Since that time, Baypamun is the most commonly used drug for treatment of FeLV infection in Germany and other European countries. Four placebo-controlled double-blind trials were performed to determine the therapeutic efficacy of Baypamun and other compounds in naturally FeLV-infected cats under controlled conditions.

  15. Prevalence of avian respiratory viruses in broiler flocks in Egypt.

    PubMed

    Hassan, Kareem E; Shany, Salama A S; Ali, A; Dahshan, Al-Hussien M; El-Sawah, Azza A; El-Kady, Magdy F

    2016-06-01

    In this study, respiratory viral pathogens were screened using real-time RT-PCR in 86 broiler chicken flocks suffering from respiratory diseases problems in 4 Egyptian governorates between January 2012 and February 2014. The mortality rates in the investigated flocks ranged from 1 to 47%. Results showed that mixed infection represented 66.3% of the examined flocks. Mixed infectious bronchitis (IBV) and avian influenza (AI)-H9N2 viruses were the most common infection (41.7%). Lack of AI-H9N2 vaccination and high rates of mixed infections in which AI-H9N2 is involved indicate an early AI-H9N2 infection with a potential immunosuppressive effect that predisposes for other viral infections. High pathogenic AI-H5N1 and virulent Newcastle disease virus (vNDV) infections were also detected (26.7% and 8.1%, respectively). Interestingly, co-infection of AI-H9N2 with either AIV-H5N1 or vNDV rarely resulted in high mortality. Partial cell-mediated immunity against similar internal AI genes, as well as virus interference between AI and vNDV, could be an explanation for this. Highly prevalent IBV and AI-H9N2 were isolated and were molecularly characterized based on S1 gene hypervariable region 3 ( HVR3: ) and hemagglutinin gene (HA) sequences, respectively. IBV strains were related to the variant group of IBV with multiple mutations in HVR3. Though AI-H9N2 viruses showed low rate of evolution in comparison to recent strains, few amino acid substitutions indicative of antibody selection pressure were observed in the HA gene. In conclusion, mixed viral infections, especially with IBV and AI-H9N2 viruses, are the predominant etiology of respiratory disease problems in broiler chickens in Egypt. Further investigations of the role of AI, IBV, and ND viruses' co-infections and interference in terms of altering the severity of clinical signs and lesions and/or generating novel reassortants within each virus are needed.

  16. [The diagnosis of hepatitis C virus infection].

    PubMed

    Gervain, Judit

    2014-06-29

    The successful therapy of hepatitis C viral infection requires that the illness is diagnosed before the development of structural changes of the liver. Testing is stepwise consisting of screening, diagnosis, and anti-viral therapy follow-up. For these steps there are different biochemical, serological, histological and molecular biological methods available. For screening, alanine aminotransferase and anti-HCV tests are used. The diagnosis of infection is confirmed using real-time polymerase chain reaction of the viral nucleic acid. Before initiation of the therapy liver biopsy is recommended to determine the level of structural changes in the liver. Alternatively, transient elastography or blood biomarkers may be also used for this purpose. Differential diagnosis should exclude the co-existence of other viral infections and chronic hepatitis due to other origin, with special attention to the presence of autoantibodies. The outcome of the antiviral therapy and the length of treatment are mainly determined by the viral genotype. In Hungary, most patients are infected with genotype 1, subtype b. The polymorphism type that occurs in the single nucleotide located next to the interleukin 28B region in chromosome 19 and the viral polymorphism type Q80K for infection with HCV 1a serve as predictive therapeutic markers. The follow-up of therapy is based on the quantitative determination of viral nucleic acid according to national and international protocols and should use the same method and laboratory throughout the treatment of an individual patient.

  17. ISG15 Is Upregulated in Respiratory Syncytial Virus Infection and Reduces Virus Growth through Protein ISGylation

    PubMed Central

    González-Sanz, Rubén; Mata, Manuel; Bermejo-Martín, Jesús; Álvarez, Amparo; Cortijo, Julio; Melero, José A.

    2016-01-01

    ABSTRACT Human respiratory syncytial virus (RSV), for which neither a vaccine nor an effective therapeutic treatment is currently available, is the leading cause of severe lower respiratory tract infections in children. Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like protein that is highly increased during viral infections and has been reported to have an antiviral or a proviral activity, depending on the virus. Previous studies from our laboratory demonstrated strong ISG15 upregulation during RSV infection in vitro. In this study, an in-depth analysis of the role of ISG15 in RSV infection is presented. ISG15 overexpression and small interfering RNA (siRNA)-silencing experiments, along with ISG15 knockout (ISG15−/−) cells, revealed an anti-RSV effect of the molecule. Conjugation inhibition assays demonstrated that ISG15 exerts its antiviral activity via protein ISGylation. This antiviral activity requires high levels of ISG15 to be present in the cells before RSV infection. Finally, ISG15 is also upregulated in human respiratory pseudostratified epithelia and in nasopharyngeal washes from infants infected with RSV, pointing to a possible antiviral role of the molecule in vivo. These results advance our understanding of the innate immune response elicited by RSV and open new possibilities to control infections by the virus. IMPORTANCE At present, no vaccine or effective treatment for human respiratory syncytial virus (RSV) is available. This study shows that interferon-stimulated gene 15 (ISG15) lowers RSV growth through protein ISGylation. In addition, ISG15 accumulation highly correlates with the RSV load in nasopharyngeal washes from children, indicating that ISG15 may also have an antiviral role in vivo. These results improve our understanding of the innate immune response to RSV and identify ISG15 as a potential target for virus control. PMID:26763998

  18. Success and failure of virus-specific T cell responses in hepatitis C virus infection.

    PubMed

    Neumann-Haefelin, Christoph; Thimme, Robert

    2011-01-01

    Hepatitis C virus (HCV) infection is only cleared in a minority of infected individuals, the majority of patients develop chronic infection. Chronic HCV infection potentially leads to liver fibrosis, cirrhosis and finally hepatocellular carcinoma. The host immune response is an important determinant in the outcome of HCV infection. Innate as well as adaptive cellular and humoral immune responses mediate important antiviral actions; however, virus-specific T cell responses appear to be most critical. Indeed, strong and multispecific CD4+ as well as CD8+ T cell responses are required for viral clearance. Interestingly, individuals who express certain HLA alleles (which are important for antigen presentation to CD4+ and CD8+ T cells) have a higher chance to clear the virus. The mechanisms of protection by HLA class I alleles such as HLA-B27 have been characterized recently. In most individuals, however, the HCV-specific immune response fails to clear the virus. Several mechanisms underlying this HCV-specific T cell failure have been identified. These include viral factors such as viral escape mutations and immunological factors such as the expression of inhibitory receptors, which lead to CD8+ T cell dysfunction. An in-depth understanding of the determinants of success or failure of the HCV-specific T cell response is critical for the development of prophylactic as well as therapeutic vaccination regimes against HCV. Here, we will discuss the virological and immunological determinants of HCV clearance and persistence.

  19. Atypical serological profiles in hepatitis B virus infection.

    PubMed

    Pondé, Robério A A

    2013-04-01

    During hepatitis B virus (HBV) infection, at least four antigen-antibody systems are observed: HBsAg and anti-HBs; preS antigen and anti-preS antibody; HBcAg and anti-HBc; and HBeAg and anti-HBe. Through the examination of these antigen-antibody systems, hepatitis B infection is diagnosed and the course of the disorder may be observed. Although the serologic findings that allow both the diagnosis of HBV infection as well as assessing of its clinical course are already well established, the dynamics of viral proteins expression and of the antibodies production may vary during the infection natural course. This causes the HBV infection to be occasionally associated with the presence of uncommon serological profiles, which could lead to doubts in the interpretation of results or suspicion of a serological result being incorrect. This paper is dedicated to the discussion of some of these profiles and their significance.

  20. Proteasome Inhibition Suppresses Dengue Virus Egress in Antibody Dependent Infection

    PubMed Central

    Costa, Vivian V.; Tan, Hwee Cheng; Horrevorts, Sophie; Ooi, Eng Eong

    2015-01-01

    The mosquito-borne dengue virus (DENV) is a cause of significant global health burden, with an estimated 390 million infections occurring annually. However, no licensed vaccine or specific antiviral treatment for dengue is available. DENV interacts with host cell factors to complete its life cycle although this virus-host interplay remains to be fully elucidated. Many studies have identified the ubiquitin proteasome pathway (UPP) to be important for successful DENV production, but how the UPP contributes to DENV life cycle as host factors remains ill defined. We show here that proteasome inhibition decouples infectious virus production from viral RNA replication in antibody-dependent infection of THP-1 cells. Molecular and imaging analyses in β-lactone treated THP-1 cells suggest that proteasome function does not prevent virus assembly but rather DENV egress. Intriguingly, the licensed proteasome inhibitor, bortezomib, is able to inhibit DENV titers at low nanomolar drug concentrations for different strains of all four serotypes of DENV in primary monocytes. Furthermore, bortezomib treatment of DENV-infected mice inhibited the spread of DENV in the spleen as well as the overall pathological changes. Our findings suggest that preventing DENV egress through proteasome inhibition could be a suitable therapeutic strategy against dengue. PMID:26565697

  1. Individual Correlates of Infectivity of Influenza A Virus Infections in Households

    PubMed Central

    Tsang, Tim K.; Fang, Vicky J.; Chan, Kwok-Hung; Ip, Dennis K. M.; Leung, Gabriel M.; Peiris, J. S. Malik; Cauchemez, Simon

    2016-01-01

    Background Identifying individual correlates of infectivity of influenza virus is important for disease control and prevention. Viral shedding is used as a proxy measure of infectivity in many studies. However, the evidence for this is limited. Methods In a detailed study of influenza virus transmission within households in 2008–12, we recruited index cases with confirmed influenza infection from outpatient clinics, and followed up their household contacts for 7–10 days to identify secondary infections. We used individual-based hazard models to characterize the relationship between individual viral shedding and individual infectivity. Results We analyzed 386 households with 1147 household contacts. Index cases were separated into 3 groups according to their estimated level of viral shedding at symptom onset. We did not find a statistically significant association of virus shedding with transmission. Index cases in medium and higher viral shedding groups were estimated to have 21% (95% CI: -29%, 113%) and 44% (CI: -16%, 167%) higher infectivity, compared with those in the lower viral shedding group. Conclusions Individual viral load measured by RT-PCR in the nose and throat was at most weakly correlated with individual infectivity in households. Other correlates of infectivity should be examined in future studies. PMID:27153194

  2. Avian influenza virus RNA extraction.

    PubMed

    Spackman, Erica; Lee, Scott A

    2014-01-01

    The efficient extraction and purification of viral RNA is critical for down-stream molecular applications whether it is the sensitive and specific detection of virus in clinical samples, virus gene cloning and expression, or quantification of avian influenza (AI) virus by molecular methods from experimentally infected birds. Samples can generally be divided into two types; enriched (e.g. virus stocks) and clinical. Clinical type samples, which may be tissues or swab material, are the most difficult to process due to the complex sample composition and possibly low virus titers. In this chapter two well established procedures for the isolation of AI virus RNA from common clinical specimen types and enriched virus stocks for further molecular applications will be presented.

  3. Modelling Virus and Antibody Dynamics during Dengue Virus Infection Suggests a Role for Antibody in Virus Clearance.

    PubMed

    Clapham, Hannah E; Quyen, Than Ha; Kien, Duong Thi Hue; Dorigatti, Ilaria; Simmons, Cameron P; Ferguson, Neil M

    2016-05-01

    Dengue is an infection of increasing global importance, yet uncertainty remains regarding critical aspects of its virology, immunology and epidemiology. One unanswered question is how infection is controlled and cleared during a dengue infection. Antibody is thought to play a role, but little past work has examined the kinetics of both virus and antibody during natural infections. We present data on multiple virus and antibody titres measurements recorded sequentially during infection from 53 Vietnamese dengue patients. We fit mechanistic mathematical models of the dynamics of viral replication and the host immune response to these data. These models fit the data well. The model with antibody removing virus fits the data best, but with a role suggested for ADCC or other infected cell clearance mechanisms. Our analysis therefore shows that the observed viral and antibody kinetics are consistent with antibody playing a key role in controlling viral replication. This work gives quantitative insight into the relationship between antibody levels and the efficiency of viral clearance. It will inform the future development of mechanistic models of how vaccines and antivirals might modify the course of natural dengue infection.

  4. Health care-associated hepatitis C virus infection

    PubMed Central

    Pozzetto, Bruno; Memmi, Meriam; Garraud, Olivier; Roblin, Xavier; Berthelot, Philippe

    2014-01-01

    Hepatitis C virus (HCV) is a blood-borne pathogen that has a worldwide distribution and infects millions of people. Care-associated HCV infections represented a huge part of hepatitis C burden in the past via contaminated blood and unsafe injections and continue to be a serious problem of public health. The present review proposes a panorama of health care-associated HCV infections via the three mode of contamination that have been identified: (1) infected patient to non-infected patient; (2) infected patient to non-infected health care worker (HCW); and (3) infected HCW to non infected patient. For each condition, the circumstances of contamination are described together with the means to prevent them. As a whole, the more important risk is represented by unsafe practices regarding injections, notably with the improper use of multidose vials used for multiple patients. The questions of occupational exposures and infected HCWs are also discussed. In terms of prevention and surveillance, the main arm for combating care-associated HCV infections is the implementation of standard precautions in all the fields of cares, with training programs and audits to verify their good application. HCWs must be sensitized to the risk of blood-borne pathogens, notably by the use of safety devices for injections and good hygiene practices in the operating theatre and in all the invasive procedures. The providers performing exposed-prone procedures must monitor their HCV serology regularly in order to detect early any primary infection and to treat it without delay. With the need to stay vigilant because HCV infection is often a hidden risk, it can be hoped that the number of people infected by HCV via health care will decrease very significantly in the next years. PMID:25516637

  5. Health care-associated hepatitis C virus infection.

    PubMed

    Pozzetto, Bruno; Memmi, Meriam; Garraud, Olivier; Roblin, Xavier; Berthelot, Philippe

    2014-12-14

    Hepatitis C virus (HCV) is a blood-borne pathogen that has a worldwide distribution and infects millions of people. Care-associated HCV infections represented a huge part of hepatitis C burden in the past via contaminated blood and unsafe injections and continue to be a serious problem of public health. The present review proposes a panorama of health care-associated HCV infections via the three mode of contamination that have been identified: (1) infected patient to non-infected patient; (2) infected patient to non-infected health care worker (HCW); and (3) infected HCW to non infected patient. For each condition, the circumstances of contamination are described together with the means to prevent them. As a whole, the more important risk is represented by unsafe practices regarding injections, notably with the improper use of multidose vials used for multiple patients. The questions of occupational exposures and infected HCWs are also discussed. In terms of prevention and surveillance, the main arm for combating care-associated HCV infections is the implementation of standard precautions in all the fields of cares, with training programs and audits to verify their good application. HCWs must be sensitized to the risk of blood-borne pathogens, notably by the use of safety devices for injections and good hygiene practices in the operating theatre and in all the invasive procedures. The providers performing exposed-prone procedures must monitor their HCV serology regularly in order to detect early any primary infection and to treat it without delay. With the need to stay vigilant because HCV infection is often a hidden risk, it can be hoped that the number of people infected by HCV via health care will decrease very significantly in the next years.

  6. Feline immunodeficiency virus infection in cats of Japan.

    PubMed

    Ishida, T; Washizu, T; Toriyabe, K; Motoyoshi, S; Tomoda, I; Pedersen, N C

    1989-01-15

    A seroepidemiologic survey for feline immunodeficiency virus (FIV) infection was conducted in Japan. Between June and December 1987, individual sera (n = 3,323) were submitted by veterinary practitioners from many parts of the country. Specimens were from 1,739 cats with clinical signs suggestive of FIV infection and from 1,584 healthy-appearing cats seen by the same practitioners. The overall FIV infection rate among cats in Japan was 960/3,323 cats (28.9%). The infection rate was more than 3 times higher in the clinically ill cats, compared with that in the healthy cats of the same cohort (43.9 vs 12.4%). Male cats were 1.5 times as likely to be infected as were females. Almost all FIV-infected cats were domestic cats (as opposed to purebred cats). Complete clinical history was available for 700 of 960 FIV-infected cats. Of these 700 FIV-infected cats, 626 (89.4%) were clinically ill, and the remainder did not have clinical signs of disease. The mean age at the time of FIV diagnosis for the 700 cats was 5.2 years, with younger mean age for males (4.9 years) than for females (5.8 years). Most of the infected cats (94.7%) were either allowed to run outdoors or had lived outdoors before being brought into homes. The mortality for FIV-infected cats during the 6 months after diagnosis was 14.7%, and the mean age at the time of death was 5.7 years. Concurrent FeLV infection was seen in 12.4% of the FIV-infected cats, but this was not much different from the historical incidence of FeLV infection in similar groups of cats not infected with FIV.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Hepatitis B virus and its sexually transmitted infection - an update

    PubMed Central

    Inoue, Takako; Tanaka, Yasuhito

    2016-01-01

    Epidemiology: incidence and prevalence: About 5% of the world’s population has chronic hepatitis B virus (HBV) infection, and nearly 25% of carriers develop chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The prevalence of chronic HBV infection in human immunodeficiency virus (HIV)-infected individuals is 5%-15%; HIV/HBV coinfected individuals have a higher level of HBV replication, with higher rates of chronicity, reactivation, occult infection, and HCC than individuals with HBV only. The prevalence of HBV genotype A is significantly higher among men who have sex with men (MSM), compared with the rest of the population. Molecular mechanisms of infection, pathology, and symptomatology: HBV replication begins with entry into the hepatocyte. Sodium taurocholate cotransporting polypeptide was identified in 2012 as the entry receptor of HBV. Although chronic hepatitis B develops slowly, HIV/HBV coinfected individuals show more rapid progression to cirrhosis and HCC. Transmission and protection: The most common sources of HBV infection are body fluids. Hepatitis B (HB) vaccination is recommended for all children and adolescents, and all unvaccinated adults at risk for HBV infection (sexually active individuals such as MSM, individuals with occupational risk, and immunosuppressed individuals). Although HB vaccination can prevent clinical infections (hepatitis), it cannot prevent 100% of subclinical infections. Treatment and curability: The goal of treatment is reducing the risk of complications (cirrhosis and HCC). Pegylated interferon alfa and nucleos(t)ide analogues (NAs) are the current treatments for chronic HBV infection. NAs have improved the outcomes of patients with cirrhosis and HCC, and decreased the incidence of acute liver failure. PMID:28357379

  8. Treatment of mucocutaneous presentations of herpes simplex virus infections.

    PubMed

    Nikkels, Arjen F; Pièrard, Gérald E

    2002-01-01

    Infections by herpes simplex virus (HSV) types I and II are diverse and quite frequent. After primary infection, the virus establishes a life-long latency in the sensory ganglia and recrudescences may occur at an unpredictable rate. Recurrent labial and genital herpes infections represent the majority of clinical manifestations of HSV infections. Their management is currently well established using evidence-based medicine data. Primary labial herpes is generally not treated with antivirals in otherwise healthy children, although intravenous aciclovir may be offered in severe primary infections, particularly in the immunocompromised patient. The decision whether or not to treat recurrent labial herpes should be evaluated individually and depends on the frequency and severity of relapses, the impairment of the quality of life, and the cost of therapy. Patients with mild disease may benefit from topical therapy, and those with severe and frequent recurrences may be considered for intermittent or long-term oral antiviral therapy. Primary genital herpes is treated with oral or intravenous antivirals, depending on the severity of the infection and associated symptoms. Recurrent genital herpes can be managed with episodic short courses of oral antivirals in patients whose recurrences are moderate to severe and rare, and have a clear prodrome. Patients with >5 episodes/year, severe recurrences or unrecognisable prodromes may be best managed with long-term suppressive antiviral prophylaxis. HSV is also responsible for a variety of other clinical manifestations, including herpetic whitlow, neonatal infection, disseminated and atypical cutaneous infections, traumatic herpes, eczema herpeticum, and HSV-associated erythema multiforme. HSV infection may also represent a complication following cosmetic procedures of the oro-facial region, surgical and dental interventions, sun exposure and burns. Precise treatment guidelines for these HSV infections are not firmly established.

  9. Characterization of Lethal Zika Virus Infection in AG129 Mice

    PubMed Central

    Walker, Emma C.; Larkin, Katrina E.; Camacho, Erwin; Osorio, Jorge E.

    2016-01-01

    Background Mosquito-borne Zika virus (ZIKV) typically causes a mild and self-limiting illness known as Zika fever, which often is accompanied by maculopapular rash, headache, and myalgia. During the current outbreak in South America, ZIKV infection during pregnancy has been hypothesized to cause microcephaly and other diseases. The detection of ZIKV in fetal brain tissue supports this hypothesis. Because human infections with ZIKV historically have remained sporadic and, until recently, have been limited to small-scale epidemics, neither the disease caused by ZIKV nor the molecular determinants of virulence and/or pathogenicity have been well characterized. Here, we describe a small animal model for wild-type ZIKV of the Asian lineage. Methodology/Principal Findings Using mice deficient in interferon α/β and Ɣ receptors (AG129 mice), we report that these animals were highly susceptible to ZIKV infection and disease, succumbing within seven to eight days. Rapid viremic dissemination was observed in visceral organs and brain; but only was associated with severe pathologies in the brain and muscle. Finally, these results were consistent across challenge routes, age of mice, and inoculum doses. These data represent a mouse model for ZIKV that is not dependent on adapting ZIKV to intracerebral passage in mice. Conclusions/Significance Foot pad injection of AG129 mice with ZIKV represents a biologically relevant model for studying ZIKV infection and disease development following wild-type virus inoculation without the requirement for adaptation of the virus or intracerebral delivery of the virus. This newly developed Zika disease model can be exploited to identify determinants of ZIKV virulence and reveal molecular mechanisms that control the virus-host interaction, providing a framework for rational design of acute phase therapeutics and for vaccine efficacy testing. PMID:27093158

  10. Early events associated with infection of Epstein-Barr virus infection of primary B-cells.

    PubMed

    Halder, Sabyasachi; Murakami, Masanao; Verma, Subhash C; Kumar, Pankaj; Yi, Fuming; Robertson, Erle S

    2009-09-28

    Epstein Barr virus (EBV) is closely associated with the development of a vast number of human cancers. To develop a system for monitoring early cellular and viral events associated with EBV infection a self-recombining BAC containing 172-kb of the Epstein Barr virus genome BAC-EBV designated as MD1 BAC (Chen et al., 2005, J.Virology) was used to introduce an expression cassette of green fluorescent protein (GFP) by homologous recombination, and the resultant BAC clone, BAC-GFP-EBV was transfected into the HEK 293T epithelial cell line. The resulting recombinant GFP EBV was induced to produce progeny virus by chemical inducer from the stable HEK 293T BAC GFP EBV cell line and the virus was used to immortalize human primary B-cell as monitored by green fluorescence and outgrowth of the primary B cells. The infection, B-cell activation and cell proliferation due to GFP EBV was monitored by the expression of the B-cell surface antigens CD5, CD10, CD19, CD23, CD39, CD40 , CD44 and the intercellular proliferation marker Ki-67 using Flow cytometry. The results show a dramatic increase in Ki-67 which continues to increase by 6-7 days post-infection. Likewise, CD40 signals showed a gradual increase, whereas CD23 signals were increased by 6-12 hours, maximally by 3 days and then decreased. Monitoring the viral gene expression pattern showed an early burst of lytic gene expression. This up-regulation of lytic gene expression prior to latent genes during early infection strongly suggests that EBV infects primary B-cell with an initial burst of lytic gene expression and the resulting progeny virus is competent for infecting new primary B-cells. This process may be critical for establishment of latency prior to cellular transformation. The newly infected primary B-cells can be further analyzed for investigating B cell activation due to EBV infection.

  11. Antiviral therapy for human immunodeficiency virus infections.

    PubMed Central

    De Clercq, E

    1995-01-01

    Depending on the stage of their intervention with the viral replicative cycle, human immunodeficiency virus inhibitors could be divided into the following groups: (i) adsorption inhibitors (i.e., CD4 constructs, polysulfates, polysulfonates, polycarboxylates, and polyoxometalates), (ii) fusion inhibitors (i.e., plant lectins, succinylated or aconitylated albumins, and betulinic acid derivatives), (iii) uncoating inhibitors (i.e., bicyclams), (iv) reverse transcription inhibitors acting either competitively with the substrate binding site (i.e., dideoxynucleoside analogs and acyclic nucleoside phosphonates) or allosterically with a nonsubstrate binding site (i.e., non-nucleoside reverse transcriptase inhibitors), (v) integration inhibitors, (vi) DNA replication inhibitors, (vii) transcription inhibitors (i.e., antisense oligodeoxynucleotides and Tat antagonists), (viii) translation inhibitors (i.e., antisense oligodeoxynucleotides and ribozymes), (ix) maturation inhibitors (i.e., protease inhibitors, myristoylation inhibitors, and glycosylation inhibitors), and finally, (x) budding (assembly/release) inhibitors. Current knowledge, including the therapeutic potential, of these various inhibitors is discussed. In view of their potential clinical the utility, the problem of virus-drug resistance and possible strategies to circumvent this problem are also addressed. PMID:7542558

  12. Serological evidence of Ebola virus infection in Indonesian orangutans.

    PubMed

    Nidom, Chairul A; Nakayama, Eri; Nidom, Reviany V; Alamudi, Mohamad Y; Daulay, Syafril; Dharmayanti, Indi N L P; Dachlan, Yoes P; Amin, Mohamad; Igarashi, Manabu; Miyamoto, Hiroko; Yoshida, Reiko; Takada, Ayato

    2012-01-01

    Ebola virus (EBOV) and Marburg virus (MARV) belong to the family Filoviridae and cause severe hemorrhagic fever in humans and nonhuman primates. Despite the discovery of EBOV (Reston virus) in nonhuman primates and domestic pigs in the Philippines and the serological evidence for its infection of humans and fruit bats, information on the reservoirs and potential amplifying hosts for filoviruses in Asia is lacking. In this study, serum samples collected from 353 healthy Bornean orangutans (Pongo pygmaeus) in Kalimantan Island, Indonesia, during the period from December 2005 to December 2006 were screened for filovirus-specific IgG antibodies using a highly sensitive enzyme-linked immunosorbent assay (ELISA) with recombinant viral surface glycoprotein (GP) antigens derived from multiple species of filoviruses (5 EBOV and 1 MARV species). Here we show that 18.4% (65/353) and 1.7% (6/353) of the samples were seropositive for EBOV and MARV, respectively, with little cross-reactivity among EBOV and MARV antigens. In these positive samples, IgG antibodies to viral internal proteins were also detected by immunoblotting. Interestingly, while the specificity for Reston virus, which has been recognized as an Asian filovirus, was the highest in only 1.4% (5/353) of the serum samples, the majority of EBOV-positive sera showed specificity to Zaire, Sudan, Cote d'Ivoire, or Bundibugyo viruses, all of which have been found so far only in Africa. These results suggest the existence of multiple species of filoviruses or unknown filovirus-related viruses in Indonesia, some of which are serologically similar to African EBOVs, and transmission of the viruses from yet unidentified reservoir hosts into the orangutan populations. Our findings point to the need for risk assessment and continued surveillance of filovirus infection of human and nonhuman primates, as well as wild and domestic animals, in Asia.

  13. Parameters of Mosquito-Enhanced West Nile Virus Infection

    PubMed Central

    Moser, Lindsey A.; Lim, Pei-Yin; Styer, Linda M.; Kramer, Laura D.

    2015-01-01

    ABSTRACT The arthropod-borne West Nile virus (WNV) emerged in New York State in 1999 and quickly spread throughout the United States. Transmission is maintained in an enzootic cycle in which infected mosquitoes transmit the virus to susceptible hosts during probing and feeding. Arthropod-derived components within the viral inoculum are increasingly acknowledged to play a role in infection of vertebrate hosts. We previously showed that Culex tarsalis mosquito saliva and salivary gland extract (SGE) enhance the in vivo replication of WNV. Here, we characterized the effective dose, timing, and proximity of saliva and SGE administration necessary for enhancement of WNV viremia using a mouse model. Mosquito saliva and SGE enhanced viremia in a dose-dependent manner, and a single mosquito bite or as little as 0.01 μg of SGE was effective at enhancing viremia, suggesting a potent active salivary factor. Viremia was enhanced when SGE was injected in the same location as virus inoculation from 24 h before virus inoculation through 12 h after virus inoculation. These results were confirmed with mosquito saliva deposited by uninfected mosquitoes. When salivary treatment and virus inoculation were spatially separated, viremia was not enhanced. In summary, the effects of mosquito saliva and SGE were potent, long lasting, and localized, and these studies have implications for virus transmission in nature, where vertebrate hosts are fed upon by both infected and uninfected mosquitoes over time. Furthermore, our model provides a robust system to identify the salivary factor(s) responsible for enhancement of WNV replication. IMPORTANCE Mosquito-borne viruses are a significant class of agents causing emerging infectious diseases. WNV has caused over 18,000 cases of neuroinvasive disease in the United States since its emergence. We have shown that Culex tarsalis mosquito saliva and SGE enhance the replication of WNV. We now demonstrate that saliva and SGE have potent, long

  14. IL-27 Limits Type 2 Immunopathology Following Parainfluenza Virus Infection

    PubMed Central

    Wagage, Sagie; Sun, Yan; Christian, David A.; Harms Pritchard, Gretchen; Fang, Qun; Buza, Elizabeth L.; Jain, Deepika; Elloso, M. Merle; López, Carolina B.; Hunter, Christopher A.

    2017-01-01

    Respiratory paramyxoviruses are important causes of morbidity and mortality, particularly of infants and the elderly. In humans, a T helper (Th)2-biased immune response to these infections is associated with increased disease severity; however, little is known about the endogenous regulators of these responses that may be manipulated to ameliorate pathology. IL-27, a cytokine that regulates Th2 responses, is produced in the lungs during parainfluenza infection, but its role in disease pathogenesis is unknown. To determine whether IL-27 limits the development of pathogenic Th2 responses during paramyxovirus infection, IL-27-deficient or control mice were infected with the murine parainfluenza virus Sendai virus (SeV). Infected IL-27-deficient mice experienced increased weight loss, more severe lung lesions, and decreased survival compared to controls. IL-27 deficiency led to increased pulmonary eosinophils, alternatively activated macrophages (AAMs), and the emergence of Th2 responses. In control mice, IL-27 induced a population of IFN-γ+/IL-10+ CD4+ T cells that was replaced by IFN-γ+/IL-17+ and IFN-γ+/IL-13+ CD4+ T cells in IL-27-deficient mice. CD4+ T cell depletion in IL-27-deficient mice attenuated weight loss and decreased AAMs. Elimination of STAT6 signaling in IL-27-deficient mice reduced Th2 responses and decreased disease severity. These data indicate that endogenous IL-27 limits pathology during parainfluenza virus infection by regulating the quality of CD4+ T cell responses and therefore may have therapeutic potential in paramyxovirus infections. PMID:28129374

  15. Herpes simplex virus 2 infection impacts stress granule accumulation.

    PubMed

    Finnen, Renée L; Pangka, Kyle R; Banfield, Bruce W

    2012-08-01

    Interference with stress granule (SG) accumulation is gaining increased appreciation as a common strategy used by diverse viruses to facilitate their replication and to cope with translational arrest. Here, we examined the impact of infection by herpes simplex virus 2 (HSV-2) on SG accumulation by monitoring the localization of the SG components T cell internal antigen 1 (TIA-1), Ras-GTPase-activating SH3-domain-binding protein (G3BP), and poly(A)-binding protein (PABP). Our results indicate that SGs do not accumulate in HSV-2-infected cells and that HSV-2 can interfere with arsenite-induced SG accumulation early after infection. Surprisingly, SG accumulation was inhibited despite increased phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), implying that HSV-2 encodes previously unrecognized activities designed to maintain translation initiation downstream of eIF2α. SG accumulation was not inhibited in HSV-2-infected cells treated with pateamine A, an inducer that works independently of eIF2α phosphorylation. The SGs that accumulated following pateamine A treatment of infected cells contained G3BP and PABP but were largely devoid of TIA-1. We also identified novel nuclear structures containing TIA-1 that form late in infection. These structures contain the RNA binding protein 68-kDa Src-associated in mitosis (Sam68) and were noticeably absent in infected cells treated with inhibitors of viral DNA replication, suggesting that they arise as a result of late events in the virus replicative cycle.

  16. Preparation and efficacy of an inactivated subunit vaccine (NFUIBHK) against type 2 Herpes simplex virus infection.

    PubMed

    Skinner, G R; Williams, D R; Buchan, A; Whitney, J; Harding, M; Bodfish, K

    1978-11-17

    A vaccine against Herpes simplex virus infection was prepared by Nonidet NP 40 and formalin treatment of a type 1, infected-cell extract; virus particles were removed by ultracentrifugation over sucrose. These procedures were not detrimental to the antigenic quality of the vaccine preparation. The vaccine afforded significant protection to experimental type 2 genital herpes virus infection in mice, as adjudged by clinical observations, cytopathological change, and virus yields.

  17. Inhibition of Bim enhances replication of varicella-zoster virus and delays plaque formation in virus-infected cells.

    PubMed

    Liu, Xueqiao; Cohen, Jeffrey I

    2014-01-01

    Programmed cell death (apoptosis) is an important host defense mechanism against intracellular pathogens, such as viruses. Accordingly, viruses have evolved multiple mechanisms to modulate apoptosis to enhance replication. Varicella-zoster virus (VZV) induces apoptosis in human fibroblasts and melanoma cells. We found that VZV triggered the phosphorylation of the proapoptotic proteins Bim and BAD but had little or no effect on other Bcl-2 family members. Since phosphorylation of Bim and BAD reduces their proapoptotic activity, this may prevent or delay apoptosis in VZV-infected cells. Phosphorylation of Bim but not BAD in VZV-infected cells was dependent on activation of the MEK/extracellular signal-regulated kinase (ERK) pathway. Cells knocked down for Bim showed delayed VZV plaque formation, resulting in longer survival of VZV-infected cells and increased replication of virus, compared with wild-type cells infected with virus. Conversely, overexpression of Bim resulted in earlier plaque formation, smaller plaques, reduced virus replication, and increased caspase 3 activity. Inhibition of caspase activity in VZV-infected cells overexpressing Bim restored levels of virus production similar to those seen with virus-infected wild-type cells. Previously we showed that VZV ORF12 activates ERK and inhibits apoptosis in virus-infected cells. Here we found that VZV ORF12 contributes to Bim and BAD phosphorylation. In summary, VZV triggers Bim phosphorylation; reduction of Bim levels results in longer survival of VZV-infected cells and increased VZV replication.

  18. Molecular Biology and Infection of Hepatitis E Virus

    PubMed Central

    Nan, Yuchen; Zhang, Yan-Jin

    2016-01-01

    Hepatitis E virus (HEV) is a viral pathogen transmitted primarily via fecal-oral route. In humans, HEV mainly causes acute hepatitis and is responsible for large outbreaks of hepatitis across the world. The case fatality rate of HEV-induced hepatitis ranges from 0.5 to 3% in young adults and up to 30% in infected pregnant women. HEV strains infecting humans are classified into four genotypes. HEV strains from genotypes 3 and 4 are zoonotic, whereas those from genotypes 1 and 2 have no known animal reservoirs. Recently, notable progress has been accomplished for better understanding of HEV biology and infection, such as chronic HEV infection, in vitro cell culture system, quasi-enveloped HEV virions, functions of the HEV proteins, mechanism of HEV antagonizing host innate immunity, HEV pathogenesis and vaccine development. However, further investigation on the cross-species HEV infection, host tropism, vaccine efficacy, and HEV-specific antiviral strategy is still needed. This review mainly focuses on molecular biology and infection of HEV and offers perspective new insight of this enigmatic virus. PMID:27656178

  19. Frontiers in the Treatment of Hepatitis C Virus Infection

    PubMed Central

    Ahn, Joseph

    2014-01-01

    In the United States, chronic hepatitis C virus (HCV) infection is the leading cause of blood-borne, virus-associated death related to advanced liver disease and the leading indication for liver transplantation. Although the diagnostic test for HCV has been available for more than 20 years, the majority of persons with HCV infection still have not received a diagnosis. This has led to a recent change in screening recommendations by the Centers for Disease Control and Prevention. Moreover, new medications were approved in 2011 after nearly a decade of minimal progress in the development of treatments for HCV infection. This was followed by the highly anticipated approval of sofosbuvir and simeprevir in 201 3. In the past 3 years, there has been an explosion of reports on medications from different classes, promising a dramatic expansion to an all-oral regimen for the treatment of HCV genotype 1 infection within the next few years. This article reviews the current screening recommendations and standard of care for treatment of HCV infection and highlights specific agents in the pipeline that should change the landscape of how HCV infection is treated in the near future. PMID:24803873

  20. Modeling Powassan virus infection in Peromyscus leucopus, a natural host

    PubMed Central

    Meade-White, Kimberly; Saturday, Greg; Scott, Dana; Bloom, Marshall E.

    2017-01-01

    The tick-borne flavivirus, Powassan virus (POWV) causes life-threatening encephalitis in humans in North America and Europe. POWV is transmitted by ixodid tick vectors that feed on small to medium-sized mammals, such as Peromyscus leucopus mice, which may serve as either reservoir, bridge or amplification hosts. Intraperitoneal and intracranial inoculation of 4-week old Peromyscus leucopus mice with 103 PFU of POWV did not result in overt clinical signs of disease. However, following intracranial inoculation, infected mice seroconverted to POWV and histopathological examinations revealed that the mice uniformly developed mild lymphocytic perivascular cuffing and microgliosis in the brain and spinal cord from 5 to 15 days post infection (dpi), suggesting an early inflammatory response. In contrast, intracranial inoculation of 4-week old C57BL/6 and BALB/c mice was lethal by 5 dpi. Intraperitoneal inoculation was lethal in BALB/c mice, but 40% (2/5) of C57BL/6 mice survived. We concluded that Peromyscus leucopus mice infected i.c. with a lethal dose of POWV support a limited infection, restricted to the central nervous system and mount an antibody response to the virus. However, they fail to develop clinical signs of disease and are able to control the infection. These results suggest the involvement of restriction factors, and the mechanism by which Peromyscus leucopus mice restrict POWV infection remains under study. PMID:28141800

  1. Chayote mosaic virus, a New Tymovirus Infecting Cucurbitaceae.

    PubMed

    Bernal, J J; Jiménez, I; Moreno, M; Hord, M; Rivera, C; Koenig, R; Rodríguez-Cerezo, E

    2000-10-01

    ABSTRACT Chayote mosaic virus (ChMV) is a putative tymovirus isolated from chayote crops in Costa Rica. ChMV was characterized at the host range, serological, and molecular levels. ChMV was transmitted mechanically and induced disease symptoms mainly in Cucurbitaceae hosts. Asymptomatic infections were detected in other host families. Serologically, ChMV is related to the Andean potato latent virus (APLV) and the Eggplant mosaic virus (EMV), both members of the genus Tymovirus infecting solanaceous hosts in the Caribbean Basin and South America. The sequence of the genomic RNA of ChMV was determined and its genetic organization was typical of tymoviruses. Comparisons with other tymoviral sequences showed that ChMV was a new member of the genus Tymovirus. The phylogenetic analyses of the coat protein gene were consistent with serological comparisons and positioned ChMV within a cluster of tymoviruses infecting mainly cucurbit or solanaceous hosts, including APLV and EMV. Phylogenetic analyses of the replicase protein gene confirmed the close relationship of ChMV and EMV. Our results suggest that ChMV is related to two tymoviruses (APLV and EMV) of proximal geographical provenance but with different natural host ranges. ChMV is the first cucurbit-infecting tymovirus to be fully characterized at the genomic level.

  2. Activated mouse eosinophils protect against lethal respiratory virus infection.

    PubMed

    Percopo, Caroline M; Dyer, Kimberly D; Ochkur, Sergei I; Luo, Janice L; Fischer, Elizabeth R; Lee, James J; Lee, Nancy A; Domachowske, Joseph B; Rosenberg, Helene F

    2014-01-30

    Eosinophils are recruited to the airways as a prominent feature of the asthmatic inflammatory response where they are broadly perceived as promoting pathophysiology. Respiratory virus infections exacerbate established asthma; however, the role of eosinophils and the nature of their interactions with respiratory viruses remain uncertain. To explore these questions, we established acute infection with the rodent pneumovirus, pneumonia virus of mice (PVM), in 3 distinct mouse models of Th2 cytokine-driven asthmatic inflammation. We found that eosinophils recruited to the airways of otherwise naïve mice in response to Aspergillus fumigatus, but not ovalbumin sensitization and challenge, are activated by and degranulate specifically in response to PVM infection. Furthermore, we demonstrate that activated eosinophils from both Aspergillus antigen and cytokine-driven asthma models are profoundly antiviral and promote survival in response to an otherwise lethal PVM infection. Thus, although activated eosinophils within a Th2-polarized inflammatory response may have pathophysiologic features, they are also efficient and effective mediators of antiviral host defense.

  3. Zika virus infection damages the testes in mice.

    PubMed

    Govero, Jennifer; Esakky, Prabagaran; Scheaffer, Suzanne M; Fernandez, Estefania; Drury, Andrea; Platt, Derek J; Gorman, Matthew J; Richner, Justin M; Caine, Elizabeth A; Salazar, Vanessa; Moley, Kelle H; Diamond, Michael S

    2016-12-15

    Infection of pregnant women with Zika virus (ZIKV) can cause congenital malformations including microcephaly, which has focused global attention on this emerging pathogen. In addition to transmission by mosquitoes, ZIKV can be detected in the seminal fluid of affected males for extended periods of time and transmitted sexually. Here, using a mouse-adapted African ZIKV strain (Dakar 41519), we evaluated the consequences of infection in the male reproductive tract of mice. We observed persistence of ZIKV, but not the closely related dengue virus (DENV), in the testis and epididymis of male mice, and this was associated with tissue injury that caused diminished testosterone and inhibin B levels and oligospermia. ZIKV preferentially infected spermatogonia, primary spermatocytes and Sertoli cells in the testis, resulting in cell death and destruction of the seminiferous tubules. Less damage was caused by a contemporary Asian ZIKV strain (H/PF/2013), in part because this virus replicates less efficiently in mice. The extent to which these observations in mice translate to humans remains unclear, but longitudinal studies of sperm function and viability in ZIKV-infected humans seem warranted.

  4. Virus-neutralizing antibody response of mice to consecutive infection with human and avian influenza A viruses.

    PubMed

    Janulíková, J; Stropkovská, A; Bobišová, Z; Košík, I; Mucha, V; Kostolanský, F; Varečková, E

    2015-06-01

    In this work we simulated in a mouse model a naturally occurring situation of humans, who overcame an infection with epidemic strains of influenza A, and were subsequently exposed to avian influenza A viruses (IAV). The antibody response to avian IAV in mice previously infected with human IAV was analyzed. We used two avian IAV (A/Duck/Czechoslovakia/1956 (H4N6) and the attenuated virus rA/Viet Nam/1203-2004 (H5N1)) as well as two human IAV isolates (virus A/Mississippi/1/1985 (H3N2) of medium virulence and A/Puerto Rico/8/1934 (H1N1) of high virulence). Two repeated doses of IAV of H4 or of H5 virus elicited virus-specific neutralizing antibodies in mice. Exposure of animals previously infected with human IAV (of H3 or H1 subtype) to IAV of H4 subtype led to the production of antibodies neutralizing H4 virus in a level comparable with the level of antibodies against the human IAV used for primary infection. In contrast, no measurable levels of virus-neutralizing (VN) antibodies specific to H5 virus were detected in mice infected with H5 virus following a previous infection with human IAV. In both cases the secondary infection with avian IAV led to a significant increase of the titer of VN antibodies specific to the corresponding human virus used for primary infection. Moreover, cross-reactive HA2-specific antibodies were also induced by sequential infection. By virtue of these results we suggest that the differences in the ability of avian IAV to induce specific antibodies inhibiting virus replication after previous infection of mice with human viruses can have an impact on the interspecies transmission and spread of avian IAV in the human population.

  5. Raman spectroscopy-based screening of IgM positive and negative sera for dengue virus infection

    NASA Astrophysics Data System (ADS)

    Bilal, M.; Saleem, M.; Bilal, Maria; Ijaz, T.; Khan, Saranjam; Ullah, Rahat; Raza, A.; Khurram, M.; Akram, W.; Ahmed, M.

    2016-11-01

    A statistical method based on Raman spectroscopy for the screening of immunoglobulin M (IgM) in dengue virus (DENV) infected human sera is presented. In total, 108 sera samples were collected and their antibody indexes (AI) for IgM were determined through enzyme-linked immunosorbent assay (ELISA). Raman spectra of these samples were acquired using a 785 nm wavelength excitation laser. Seventy-eight Raman spectra were selected randomly and unbiasedly for the development of a statistical model using partial least square (PLS) regression, while the remaining 30 were used for testing the developed model. An R-square (r 2) value of 0.929 was determined using the leave-one-sample-out (LOO) cross validation method, showing the validity of this model. It considers all molecular changes related to IgM concentration, and describes their role in infection. A graphical user interface (GUI) platform has been developed to run a developed multivariate model for the prediction of AI of IgM for blindly tested samples, and an excellent agreement has been found between model predicted and clinically determined values. Parameters like sensitivity, specificity, accuracy, and area under receiver operator characteristic (ROC) curve for these tested samples are also reported to visualize model performance.

  6. Temporal Analysis of Andes Virus and Sin Nombre Virus Infections of Syrian Hamsters▿

    PubMed Central

    Wahl-Jensen, Victoria; Chapman, Jennifer; Asher, Ludmila; Fisher, Robert; Zimmerman, Michael; Larsen, Tom; Hooper, Jay W.

    2007-01-01

    Andes virus (ANDV) and Sin Nombre virus (SNV) are rodent-borne hantaviruses that cause a highly lethal hemorrhagic fever in humans known as hantavirus pulmonary syndrome (HPS). There are no vaccines or specific drugs to prevent or treat HPS, and the pathogenesis is not understood. Syrian hamsters infected with ANDV, but not SNV, develop a highly lethal disease that closely resembles HPS in humans. Here, we performed a temporal pathogenesis study comparing ANDV and SNV infections in hamsters. SNV was nonpathogenic and viremia was not detected despite the fact that all animals were infected. ANDV was uniformly lethal with a mean time to death of 11 days. The first pathology detected was lymphocyte apoptosis starting on day 4. Animals were viremic and viral antigen was first observed in multiple organs by days 6 and 8, respectively. Levels of infectious virus in the blood increased 4 to 5 logs between days 6 and 8. Pulmonary edema was first detected ultrastructurally on day 6. Ultrastructural analysis of lung tissues revealed the presence of large inclusion bodies and substantial numbers of vacuoles within infected endothelial cells. Paraendothelial gaps were not observed, suggesting that fluid leakage was transcellular and directly attributable to infecting virus. Taken together, these data imply that HPS treatment strategies aimed at preventing virus replication and dissemination will have the greatest probability of success if administered before the viremic phase; however, because vascular leakage is associated with infected endothelial cells, a therapeutic strategy targeting viral replication might be effective even at later times (e.g., after disease onset). PMID:17475651

  7. Tuberculous meningitis in patients infected with human immunodeficiency virus.

    PubMed

    Garg, Ravindra Kumar; Sinha, Manish Kumar

    2011-01-01

    Tuberculosis is the most common opportunistic infection in human immunodeficiency virus (HIV) infected persons. HIV-infected patients have a high incidence of tuberculous meningitis as well. The exact incidence and prevalence of tuberculous meningitis in HIV-infected patients are not known. HIV infection does not significantly alter the clinical manifestations, laboratory, radiographic findings, or the response to therapy. Still, some differences have been noted. For example, the histopathological examination of exudates in HIV-infected patients shows fewer lymphocytes, epithelioid cells, and Langhan's type of giant cells. Larger numbers of acid-fast bacilli may be seen in the cerebral parenchyma and meninges. The chest radiograph is abnormal in up to 46% of patients with tuberculous meningitis. Tuberculous meningitis is likely to present with cerebral infarcts and mass lesions. Cryptococcal meningitis is important in differential diagnosis. The recommended duration of treatment in HIV-infected patients is 9-12 months. The benefit of adjunctive corticosteroids is uncertain. Antiretroviral therapy and antituberculosis treatment should be initiated at the same time, regardless of CD4 cell counts. Tuberculous meningitis may be a manifestation of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome. Some studies have demonstrated a significant impact of HIV co-infection on mortality from tuberculous meningitis. HIV-infected patients with multidrug-resistant tuberculous meningitis have significantly higher mortality. The best way to prevent HIV-associated tuberculous meningitis is to diagnose and isolate infectious cases of tuberculosis promptly and administer appropriate treatment.

  8. The Relationships between Respiratory Virus Infection and Aminotransferase in Children

    PubMed Central

    Oh, Jun Suk; Choi, Jun Sik; Lee, Young Hyuk; Ko, Kyung Og; Lim, Jae Woo; Cheon, Eun Jung; Lee, Gyung Min

    2016-01-01

    Purpose We sought to examine the relationship between the clinical manifestations of nonspecific reactive hepatitis and respiratory virus infection in pediatric patients. Methods Patients admitted to the pediatric unit of Konyang University Hospital for lower respiratory tract disease between January 1, 2014 and December 31, 2014 and who underwent reverse transcriptase polymerase chain reaction tests were examined. The patients were divided into those with increased levels of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) and those with normal ALT or AST levels. Further, patients with increased ALT and AST levels were individually compared with patients in the normal group, and the blood test results were compared according to the type of respiratory virus. Results Patients with increased ALT or AST levels had one more day of hospital stay, on average, compared with patients in the normal group (5.3±3.1 days vs. 4.4±3.0 days, p=0.019). Patients in the increased ALT level group were younger and had a longer mean hospital stay, compared with patients in the normal group (p=0.022 and 0.003, respectively). The incidences of increased ALT or AST were the highest in adenovirus infections (6/24, 25.0%), followed by enterovirus (2/11, 18.2%) and respiratory syncytial virus A (21/131, 16.0%) infections. Conclusion Nonspecific reactive hepatitis is more common among patients with adenovirus, enterovirus and respiratory syncytial virus infection, as well as among those infected at a younger age. Compared with AST levels, ALT levels are better indicators of the severity of nonspecific reactive hepatitis. PMID:28090469

  9. Begomoviruses infecting weeds in Cuba: increased host range and a novel virus infecting Sida rhombifolia.

    PubMed

    Fiallo-Olivé, Elvira; Navas-Castillo, Jesús; Moriones, Enrique; Martínez-Zubiaur, Yamila

    2012-01-01

    As a result of surveys conducted during the last few years to search for wild reservoirs of begomoviruses in Cuba, we detected a novel bipartite begomovirus, sida yellow mottle virus (SiYMoV), infecting Sida rhombifolia plants. The complete genome sequence was obtained, showing that DNA-A was 2622 nucleotides (nt) in length and that it was most closely related (87.6% nucleotide identity) to DNA-A of an isolate of sida golden mosaic virus (SiGMV) that infects snap beans (Phaseolus vulgaris) in Florida. The DNA-B sequence was 2600 nt in length and shared the highest nucleotide identity (75.1%) with corchorus yellow spot virus (CoYSV). Phylogenetic relationship analysis showed that both DNA components of SiYMoV were grouped in the Abutilon clade, along with begomoviruses from Florida and the Caribbean islands. We also present here the complete nucleotide sequence of a novel strain of sida yellow vein virus found infecting Malvastrum coromandelianum and an isolate of euphorbia mosaic virus that was found for the first time infecting Euphorbia heterophylla in Cuba.

  10. Considerations in the Use of Nonhuman Primate Models of Ebola Virus and Marburg Virus Infection.

    PubMed

    Geisbert, Thomas W; Strong, James E; Feldmann, Heinz

    2015-10-01

    The filoviruses, Ebola virus and Marburg virus, are zoonotic pathogens that cause severe hemorrhagic fever in humans and nonhuman primates (NHPs), with case-fatality rates ranging from 23% to 90%. The current outbreak of Ebola virus infection in West Africa, with >26 000 cases, demonstrates the long-underestimated public health danger that filoviruses pose as natural human pathogens. Currently, there are no vaccines or treatments licensed for human use. Licensure of any medical countermeasure may require demonstration of efficacy in the gold standard cynomolgus or rhesus macaque models of filovirus infection. Substantial progress has been made over the last decade in characterizing the filovirus NHP models. However, there is considerable debate over a variety of experimental conditions, including differences among filovirus isolates used, routes and doses of exposure, and euthanasia criteria, all of which may contribute to variability of results among different laboratories. As an example of the importance of understanding these differences, recent data with Ebola virus shows that an addition of a single uridine residue in the glycoprotein gene at the editing site attenuates the virus. Here, we draw on decades of experience working with filovirus-infected NHPs to provide a perspective on the importance of various experimental conditions.

  11. Hepatitis A virus infections in Voyvodina.

    PubMed Central

    Vuković, B. S.; Rončević, N.; Borota, R.; Terzin, A. L.

    1981-01-01

    Sera of 1000 persons in Voyvodina were tested with radioimmunoassay for antibodies against hepatitis A virus (HAV). The morbidity and age incidence of positive findings have been analysed and compared with relevant findings in other countries. Below the age of 19 years the morbidity rates are higher (0.138 to 0.595 per mill) and the prevalences of seropositives are lower (17.1-64.0%) than the respective frequencies above that age (0.011 to 0.052 per mill and 85.7-98.7% respectively). Below the first year of life seropositivity is more frequent than in 1- to 14-year old children. After the first year until the age of 30-39 years the frequency of seropositives increases with increasing age up to a maximum of about 90%. PMID:6257777

  12. West Nile virus infection of birds, Mexico.

    PubMed

    Guerrero-Sánchez, Sergio; Cuevas-Romero, Sandra; Nemeth, Nicole M; Trujillo-Olivera, María Teresa Jesús; Worwa, Gabriella; Dupuis, Alan; Brault, Aaron C; Kramer, Laura D; Komar, Nicholas; Estrada-Franco, José Guillermo

    2011-12-01

    West Nile virus (WNV) has caused disease in humans, equids, and birds at lower frequency in Mexico than in the United States. We hypothesized that the seemingly reduced virulence in Mexico was caused by attenuation of the Tabasco strain from southeastern Mexico, resulting in lower viremia than that caused by the Tecate strain from the more northern location of Baja California. During 2006-2008, we tested this hypothesis in candidate avian amplifying hosts: domestic chickens, rock pigeons, house sparrows, great-tailed grackles, and clay-colored thrushes. Only great-tailed grackles and house sparrows were competent amplifying hosts for both strains, and deaths occurred in each species. Tecate strain viremia levels were higher for thrushes. Both strains produced low-level viremia in pigeons and chickens. Our results suggest that certain avian hosts within Mexico are competent for efficient amplification of both northern and southern WNV strains and that both strains likely contribute to bird deaths.

  13. Neuropathology of H5N1 virus infection in ferrets.

    PubMed

    Peng, Bi-Hung; Yun, Nadezhda; Chumakova, Olga; Zacks, Michele; Campbell, Gerald; Smith, Jeanon; Smith, Jennifer; Linde, Seth; Linde, Jenna; Paessler, Slobodan

    2012-05-04

    Highly pathogenic H5N1 virus remains a potential threat to humans. Over 289 fatalities have been reported in WHO confirmed human cases since 2003, and lack of effective vaccines and early treatments contribute to increasing numbers of cases and fatalities. H5N1 encephalitis is a recognized cause of death in Vietnamese cases, and brain pathology is described in other human cases and naturally infected animals. However, neither pathogenesis of H5N1 viral infection in human brain nor post-infection effects in survivors have been fully investigated. We report the brain pathology in a ferret model for active infection and 18-day survival stages. This model closely resembles the infection pattern and progression in human cases of influenza A, and our report is the first description of brain pathology for longer term (18-day) survival in ferrets. We analyzed viral replication, type and severity of meningoencephalitis, infected cell types, and cellular responses to infection. We found viral replication to very high titers in ferret brain, closely correlating with severity of meningoencephalitis. Viral antigens were detected predominantly in neurons, correlating with inflammatory lesions, and less frequently in astrocytes and ependymal cells during active infection. Mononuclear cell infiltrates were observed in early stages predominantly in cerebral cortex, brainstem, and leptomeninges, and less commonly in cerebellum and other areas. Astrogliosis was mild at day 4 post-infection, but robust by day 18. Early and continuous treatment with an antiviral agent (peramivir) inhibited virus production to non-detectable levels, reduced severity of brain injury, and promoted higher survival rates.

  14. Hepatitis B virus coinfection in human immunodeficiency virus-infected patients: A review

    PubMed Central

    Sun, Hsin-Yun; Sheng, Wang-Huei; Tsai, Mao-Song; Lee, Kuan-Yeh; Chang, Sui-Yuan; Hung, Chien-Ching

    2014-01-01

    Hepatitis B virus (HBV) infection is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Due to the shared modes of transmission, coinfection with HBV and human immunodeficiency virus (HIV) is not uncommon. It is estimated that 10% of HIV-infected patients worldwide are coinfected with HBV. In areas where an HBV vaccination program is implemented, the HBV seroprevalence has declined significantly. In HIV/HBV-coinfected patients, HBV coinfection accelerates immunologic and clinical progression of HIV infection and increases the risk of hepatotoxicity when combination antiretroviral therapy (cART) is initiated, while HIV infection increases the risk of hepatitis events, cirrhosis, and end-stage liver disease related to chronic HBV infection. With the advances in antiviral therapy, concurrent, successful long-term suppression of HIV and HBV replication can be achieved in the cART era. To reduce the disease burden of HBV infection among HIV-infected patients, adoption of safe sex practices, avoidance of sharing needles and diluent, HBV vaccination and use of cART containing tenofovir disoproxil fumarate plus emtricitabine or lamivudine are the most effective approaches. However, due to HIV-related immunosuppression, using increased doses of HBV vaccine and novel approaches to HBV vaccination are needed to improve the immunogenicity of HBV vaccine among HIV-infected patients. PMID:25356024

  15. Ferrets Infected with Bundibugyo Virus or Ebola Virus Recapitulate Important Aspects of Human Filovirus Disease

    PubMed Central

    Kozak, Robert; He, Shihua; Kroeker, Andrea; de La Vega, Marc-Antoine; Audet, Jonathan; Wong, Gary; Urfano, Chantel; Antonation, Kym; Embury-Hyatt, Carissa; Kobinger, Gary P.

    2016-01-01

    ABSTRACT Bundibugyo virus (BDBV) is the etiological agent of a severe hemorrhagic fever in humans with a case-fatality rate ranging from 25 to 36%. Despite having been known to the scientific and medical communities for almost 1 decade, there is a dearth of studies on this pathogen due to the lack of a small animal model. Domestic ferrets are commonly used to study other RNA viruses, including members of the order Mononegavirales. To investigate whether ferrets were susceptible to filovirus infections, ferrets were challenged with a clinical isolate of BDBV. Animals became viremic within 4 days and succumbed to infection between 8 and 9 days, and a petechial rash was observed with moribund ferrets. Furthermore, several hallmarks of human filoviral disease were recapitulated in the ferret model, including substantial decreases in lymphocyte and platelet counts and dysregulation of key biochemical markers related to hepatic/renal function, as well as coagulation abnormalities. Virological, histopathological, and immunohistochemical analyses confirmed uncontrolled BDBV replication in the major organs. Ferrets were also infected with Ebola virus (EBOV) to confirm their susceptibility to another filovirus species and to potentially establish a virus transmission model. Similar to what was seen with BDBV, important hallmarks of human filoviral disease were observed in EBOV-infected ferrets. This study demonstrates the potential of this small animal model for studying BDBV and EBOV using wild-type isolates and will accelerate efforts to understand filovirus pathogenesis and transmission as well as the development of specific vaccines and antivirals. IMPORTANCE The 2013-2016 outbreak of Ebola virus in West Africa has highlighted the threat posed by filoviruses to global public health. Bundibugyo virus (BDBV) is a member of the genus Ebolavirus and has caused outbreaks in the past but is relatively understudied, likely due to the lack of a suitable small animal model. Such

  16. Immunological aspects of antiviral therapy of chronic hepatitis B virus and hepatitis C virus infections.

    PubMed

    Rehermann, Barbara; Bertoletti, Antonio

    2015-02-01

    Hepatitis B virus (HBV) and hepatitis C virus (HCV) cause a large proportion of acute and chronic liver disease worldwide. Over the past decades many immunological studies defined host immune responses that mediate spontaneous clearance of acute HBV and HCV infection. However, host immune responses are also relevant in the context of treatment-induced clearance of chronic HBV and HCV infection. First, the pretreatment level of interferon-stimulated genes as well as genetic determinants of innate immune responses, such as single nucleotide polymorphisms near the IFNL3 gene, are strong predictors of the response to interferon-alpha (IFN-α)-based therapy. Second, IFN-α, which has been a mainstay of HBV and HCV therapy over decades, and ribavirin, which has also been included in interferon-free direct antiviral therapy for HCV, modulate host immune responses. Third, both IFN-α-based and IFN-α-free treatment regimens of HBV and HCV infection alter the short-term and long-term adaptive immune response against these viruses. Finally, treatment studies have not just improved the clinical outcomes, but also provided opportunities to study virus-host interaction. This review summarizes our current knowledge on how a patient's immune response affects the treatment outcome of HBV and HCV infection and how innate and adaptive immune responses themselves are altered by the different treatment regimens.

  17. Seroprevalence of feline leukemia virus and feline immunodeficiency virus infection among cats in Canada.

    PubMed

    Little, Susan; Sears, William; Lachtara, Jessica; Bienzle, Dorothee

    2009-06-01

    The purposes of this study were to determine the seroprevalence of feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) infection among cats in Canada and to identify risk factors for seropositivity. Signalment, lifestyle factors, and test results for FeLV antigen and FIV antibody were analyzed for 11 144 cats from the 10 Canadian provinces. Seroprevalence for FIV antibody was 4.3% and seroprevalence for FeLV antigen was 3.4%. Fifty-eight cats (0.5%) were seropositive for both viruses. Seroprevalence varied geographically. Factors such as age, gender, health status, and lifestyle were significantly associated with risk of FeLV and FIV seropositivity. The results suggest that cats in Canada are at risk of retrovirus infection and support current recommendations that the retrovirus status of all cats should be known.

  18. Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with zika virus

    PubMed Central

    Dejnirattisai, Wanwisa; Supasa, Piyada; Wongwiwat, Wiyada; Rouvinski, Alexander; Barba-Spaeth, Giovanna; Duangchinda, Thaneeya; Sakuntabhai, Anavaj; Cao-Lormeau, Van-Mai; Malasit, Prida; Rey, Felix A; Mongkolsapaya, Juthathip; Screaton, Gavin R

    2016-01-01

    Zika virus (ZIKV) was discovered in 1947 and was thought to lead to relatively mild disease. The recent explosive outbreak of ZIKV in South America has led to widespread concern with reports of neurological sequelae ranging from Guillain Barré syndrome to microcephaly. ZIKV infection has occurred in areas previously exposed to dengue, a flavivirus closely related to ZIKV. Here we investigate the serological crossreaction between the two viruses. Dengue immune plasma substantially crossreacted with ZIKV and could drive antibody-dependent enhancement of ZIKV infection. Using a panel of human anti-dengue monoclonal antibodies we showed that most antibodies reacting to dengue envelope protein also reacted to ZIKV. Antibodies to linear epitopes including the immunodominant fusion loop epitope while able to bind ZIKV could not neutralize the virus but instead promoted ADE. These data indicate that dengue immunity may drive higher ZIKV replication and have clear implications for disease pathogenesis and future ZIKV and dengue vaccine programs. PMID:27339099

  19. Predominant Infection of CD150+ Lymphocytes and Dendritic Cells during Measles Virus Infection of Macaques

    PubMed Central

    de Swart, Rik L; Yanagi, Yusuke; van Amerongen, Geert; McQuaid, Stephen; Yüksel, Selma; Geijtenbeek, Teunis B. H; Duprex, W. Paul; Osterhaus, Albert D. M. E

    2007-01-01

    Measles virus (MV) is hypothesized to enter the host by infecting epithelial cells of the respiratory tract, followed by viremia mediated by infected monocytes. However, neither of these cell types express signaling lymphocyte activation molecule (CD150), which has been identified as the receptor for wild-type MV. We have infected rhesus and cynomolgus macaques with a recombinant MV strain expressing enhanced green fluorescent protein (EGFP); thus bringing together the optimal animal model for measles and a virus that can be detected with unprecedented sensitivity. Blood samples and broncho-alveolar lavages were collected every 3 d, and necropsies were performed upon euthanasia 9 or 15 d after infection. EGFP production by MV-infected cells was visualized macroscopically, in both living and sacrificed animals, and microscopically by confocal microscopy and FACS analysis. At the peak of viremia, EGFP fluorescence was detected in skin, respiratory and digestive tract, but most intensely in all lymphoid tissues. B- and T-lymphocytes expressing CD150 were the major target cells for MV infection. Highest percentages (up to 30%) of infected lymphocytes were detected in lymphoid tissues, and the virus preferentially targeted cells with a memory phenotype. Unexpectedly, circulating monocytes did not sustain productive MV infection. In peripheral tissues, large numbers of MV-infected CD11c+ MHC class-II+ myeloid dendritic cells were detected in conjunction with infected T-lymphocytes, suggesting transmission of MV between these cell types. Fluorescent imaging of MV infection in non-human primates demonstrated a crucial role for lymphocytes and dendritic cells in the pathogenesis of measles and measles-associated immunosuppression. PMID:18020706

  20. Is virus coinfection a predictor of severity in children with viral respiratory infections?

    PubMed

    Asner, S A; Rose, W; Petrich, A; Richardson, S; Tran, D J

    2015-03-01

    Molecular assays have resulted in increased detection of viral respiratory infections, including virus coinfection, from children with acute respiratory infections. Yet the clinical severity of virus coinfection compared to single virus infection remains uncertain. We performed a retrospective study of children presenting with acute respiratory infections comparing clinical severity of single respiratory virus infection to virus coinfection, detected on midturbinate swabs by molecular assays. Patient characteristics and measures of clinical severity were abstracted from health records. A total of 472 virus-infected children were included, 391 with a single virus infection and 81 with virus coinfection. Virus status did not affect admission to hospital (odds ratio (OR) = 0.8; 95 % confidence interval (CI) 0.5-1.4; p 0.491) or clinical disease severity among inpatients (OR = 0.8; 95% CI 0.5-1.5; p 0.515) after adjusting for age and underlying comorbidities. However, children infected with rhinovirus/enterovirus (HRV/ENT) alone were more likely to be admitted to the hospital compared to those coinfected with HRV/ENT and at least another virus, although this was not significant in multivariable analyses (OR 0.47; 95% CI 0.22-1.0; p 0.051). In multivariable analyses, children coinfected with respiratory syncytial virus (RSV) and other viruses were significantly more likely to present with radiologically confirmed pneumonia compared to those with an isolated RSV infection (OR 3.16, 95% CI 1.07-9.34, p 0.037). Equivalent clinical severity was observed between children with single virus infection and virus coinfection, although children coinfected with RSV and other viruses presented more frequently with pneumonia than those with single RSV infection. Increased disease severity observed among children with single HRV/ENT infection requires further investigation.

  1. Fluorescent tagging of herpes simplex virus tegument protein VP13/14 in virus infection.

    PubMed

    Donnelly, M; Elliott, G

    2001-03-01

    The cellular site of herpesvirus tegument assembly has yet to be defined. We have previously used a recombinant herpes simplex virus type 1 expressing a green fluorescent protein (GFP)-tagged tegument protein, namely VP22, to show that VP22 is localized exclusively to the cytoplasm during infection. Here we have constructed a similar virus expressing another fluorescent tegument protein, YFP-VP13/14, and have visualized the intracellular localization of this second tegument protein in live infected cells. In contrast to VP22, VP13/14 is targeted predominantly to the nuclei of infected cells at both early and late times in infection. More specifically, YFP-13/14 localizes initially to the nuclear replication compartments and then progresses into intense punctate domains that appear at around 12 h postinfection. At even later times this intranuclear punctate fluorescence is gradually replaced by perinuclear micropunctate and membranous fluorescence. While the vast majority of YFP-13/14 seems to be targeted to the nucleus, a minor subpopulation also appears in a vesicular pattern in the cytoplasm that closely resembles the pattern previously observed for GFP-22. Moreover, at late times weak fluorescence appears at the cell periphery and in extracellular virus particles, confirming that YFP-13/14 is assembled into virions. This predominantly nuclear targeting of YFP-13/14 together with the cytoplasmic targeting of VP22 may imply that there are multiple sites of tegument protein incorporation along the virus maturation pathway. Thus, our YFP-13/14-expressing virus has revealed the complexity of the intracellular targeting of VP13/14 and provides a novel insight into the mechanism of tegument, and hence virus, assembly.

  2. Annual Incidence of Lassa Virus Infection in Southern Mali.

    PubMed

    Safronetz, David; Sogoba, Nafomon; Diawara, Sory Ibrahim; Bane, Sidy; Rosenke, Kyle; Maiga, Ousmane; Boisen, Matt; Garry, Robert F; Branco, Luis M; Lindsay, L Robbin; Traoré, Sékou F; Feldmann, Heinz; Doumbia, Seydou

    2017-01-16

    Previously, we reported a high seroprevalence rate of Lassa virus antibodies in inhabitants of three villages in southern Mali where infected rodents have been demonstrated. Herein, we report a 1-year follow-up study in which we were able to collect a second blood samples from 88.7% of participants of the same cohort. We identified 23 seroconversions for IgG antibodies reactive against Lassa virus, representing an incidence of 6.3% (95% confidence interval = 3.8-8.8%). Seroconversion was frequently seen in preteenage children (12/23, 51.7%) and two household/familial clusters were identified. These results confirm active transmission of Lassa virus is occurring in southern Mali and appropriate diagnostic testing should be established for this often severe etiological agent viral hemorrhagic fever.

  3. Systems biology unravels interferon responses to respiratory virus infections.

    PubMed

    Kroeker, Andrea L; Coombs, Kevin M

    2014-02-26

    Interferon production is an important defence against viral replication and its activation is an attractive therapeutic target. However, it has long been known that viruses perpetually evolve a multitude of strategies to evade these host immune responses. In recent years there has been an explosion of information on virus-induced alterations of the host immune response that have resulted from data-rich omics technologies. Unravelling how these systems interact and determining the overall outcome of the host response to viral infection will play an important role in future treatment and vaccine development. In this review we focus primarily on the interferon pathway and its regulation as well as mechanisms by which respiratory RNA viruses interfere with its signalling capacity.

  4. Viruses infecting marine picoplancton encode functional potassium ion channels.

    PubMed

    Siotto, Fenja; Martin, Corinna; Rauh, Oliver; Van Etten, James L; Schroeder, Indra; Moroni, Anna; Thiel, Gerhard

    2014-10-01

    Phycodnaviruses are dsDNA viruses, which infect algae. Their large genomes encode many gene products, like small K(+) channels, with homologs in prokaryotes and eukaryotes. Screening for K(+) channels revealed their abundance in viruses from fresh-water habitats. Recent sequencing of viruses from marine algae or from salt water in Antarctica revealed sequences with the predicted characteristics of K(+) channels but with some unexpected features. Two genes encode either 78 or 79 amino acid proteins, which are the smallest known K(+) channels. Also of interest is an unusual sequence in the canonical α-helixes in K(+) channels. Structural prediction algorithms indicate that the new channels have the conserved α-helix folds but the algorithms failed to identify the expected transmembrane domains flanking the K(+) channel pores. In spite of these unexpected properties electophysiological studies confirmed that the new proteins are functional K(+) channels.

  5. Tomato bushy stunt virus (TBSV) infecting Lycopersicon esculentum.

    PubMed

    Hafez, El Sayed E; Saber, Ghada A; Fattouh, Faiza A

    2010-01-01

    Tomato bushy stunt virus (TBSV) was detected in tomato crop (Lycopersicon esculentum) in Egypt with characteristic mosaic leaf deformation, stunting, and bushy growth symptoms. TBSV infection was confirmed serologically by ELISA and calculated incidence was 25.5%. Basic physicochemical properties of a purified TBSV Egh isolate were identical to known properties of tombusviruses of isometric 30-nm diameter particles, 41-kDa coat protein and the genome of approximately 4800 nt. This is the first TBSV isolate reported in Egypt. Cloning and partial sequencing of the isolate showed that it is more closely related to TBSV-P and TBSV-Ch than TBSV-Nf and TBSV-S strains of the virus. However, it is distinct from the above strains and could be a new strain of the virus which further confirms the genetic diversity of tombusviruses.

  6. Dynein Regulators Are Important for Ecotropic Murine Leukemia Virus Infection

    PubMed Central

    Valle-Tenney, Roger; Opazo, Tatiana; Cancino, Jorge; Goff, Stephen P.

    2016-01-01

    ABSTRACT During the early steps of infection, retroviruses must direct the movement of the viral genome into the nucleus to complete their replication cycle. This process is mediated by cellular proteins that interact first with the reverse transcription complex and later with the preintegration complex (PIC), allowing it to reach and enter the nucleus. For simple retroviruses, such as murine leukemia virus (MLV), the identities of the cellular proteins involved in trafficking of the PIC in infection are unknown. To identify cellular proteins that interact with the MLV PIC, we developed a replication-competent MLV in which the integrase protein was tagged with a FLAG epitope. Using a combination of immunoprecipitation and mass spectrometry, we established that the microtubule motor dynein regulator DCTN2/p50/dynamitin interacts with the MLV preintegration complex early in infection, suggesting a direct interaction between the incoming viral particles and the dynein complex regulators. Further experiments showed that RNA interference (RNAi)-mediated silencing of either DCTN2/p50/dynamitin or another dynein regulator, NudEL, profoundly reduced the efficiency of infection by ecotropic, but not amphotropic, MLV reporters. We propose that the cytoplasmic dynein regulators are a critical component of the host machinery needed for infection by the retroviruses entering the cell via the ecotropic envelope pathway. IMPORTANCE Retroviruses must access the chromatin of host cells to integrate the viral DNA, but before this crucial event, they must reach the nucleus. The movement through the cytoplasm—a crowded environment where diffusion is slow—is thought to utilize retrograde transport along the microtubule network by the dynein complex. Different viruses use different components of this multisubunit complex. We found that the preintegration complex of murine leukemia virus (MLV) interacts with the dynein complex and that regulators of this complex are essential for

  7. High Seroprevalence of Herpes Simplex Virus Type 2 Infection in French Human Immunodeficiency Virus Type 1-Infected Outpatients

    PubMed Central

    Andréoletti, Laurent; Piednoir, Emmanuel; Legoff, Jérôme; Brodard, Véronique; Beguinot, Isabelle; Strady, Christophe; Rouger, Christine; Piketty, Christophe; Si-Mohamed, Ali; Kazatchkine, Michel Daniel; Malkin, Jean-Elie; Bélec, Laurent

    2005-01-01

    Using commercially available herpes simplex virus (HSV) type-specific serological diagnostic tests, HSV type 2 (HSV-2) antibody prevalence was assessed in two parallel prospective studies including 534 human immunodeficiency virus type 1 (HIV-1)-infected outpatients living in two areas of northern France. In the first cohort of 434 subjects, 223 (51%) individuals demonstrated a positive HSV-2 serological status while 66 (66%) of 100 subjects in the second cohort were seropositive for HSV-2 (51 versus 66%; P = 0.08). Among the 223 HSV-2-seropositive subjects identified in the first study cohort, only 22 (10%) had suffered from recurrent anogenital lesions during the past 12 months while 154 (69%) had no clinical history of herpesvirus infection. Our findings demonstrate high proportions of subclinical and undiagnosed HSV-2 infection in HIV-1-infected individuals and suggest that HSV type-specific serological testing in the French HIV-1-infected subpopulation could be an efficient strategy to diagnose clinically asymptomatic HSV-2 infections. PMID:16081982

  8. High seroprevalence of herpes simplex virus type 2 infection in French human immunodeficiency virus type 1-infected outpatients.

    PubMed

    Andréoletti, Laurent; Piednoir, Emmanuel; Legoff, Jérôme; Brodard, Véronique; Beguinot, Isabelle; Strady, Christophe; Rouger, Christine; Piketty, Christophe; Si-Mohamed, Ali; Kazatchkine, Michel Daniel; Malkin, Jean-Elie; Bélec, Laurent

    2005-08-01

    Using commercially available herpes simplex virus (HSV) type-specific serological diagnostic tests, HSV type 2 (HSV-2) antibody prevalence was assessed in two parallel prospective studies including 534 human immunodeficiency virus type 1 (HIV-1)-infected outpatients living in two areas of northern France. In the first cohort of 434 subjects, 223 (51%) individuals demonstrated a positive HSV-2 serological status while 66 (66%) of 100 subjects in the second cohort were seropositive for HSV-2 (51 versus 66%; P = 0.08). Among the 223 HSV-2-seropositive subjects identified in the first study cohort, only 22 (10%) had suffered from recurrent anogenital lesions during the past 12 months while 154 (69%) had no clinical history of herpesvirus infection. Our findings demonstrate high proportions of subclinical and undiagnosed HSV-2 infection in HIV-1-infected individuals and suggest that HSV type-specific serological testing in the French HIV-1-infected subpopulation could be an efficient strategy to diagnose clinically asymptomatic HSV-2 infections.

  9. Treatment of Hepatitis C Virus Infection in Liver Transplant Recipients

    PubMed Central

    Suraweera, Duminda; Sundaram, Vinay

    2016-01-01

    Chronic hepatitis C virus (HCV) infection is the leading cause of liver transplantation in adults. Although the recurrence of HCV infection after liver transplantation is nearly universal, the recent advances in direct-acting antiviral (DAA) agents have revolutionized the management of HCV infection in the posttransplant setting. A number of these agents have been evaluated in recent clinical trials and have shown high sustained virologic response rates, shorter durations of treatment, and decreased adverse events when compared with the previous treatment of pegylated interferon and ribavirin. This article will review the current literature on the efficacy, tolerability, and potential drug interactions of various DAA agents in patients with recurrent HCV infection posttransplant. PMID:27330501

  10. Epidemiology of hepatitis A virus infections, Germany, 2007-2008.

    PubMed

    Faber, Mirko S; Stark, Klaus; Behnke, Susanne C; Schreier, Eckart; Frank, Christina

    2009-11-01

    Approximately 60% of hepatitis A virus infections in Germany occur in persons without a travel history to disease-endemic areas and for whom sources of infection are unknown. Recommendation of pretravel vaccination fails to prevent the remaining imported infections. Using enhanced surveillance in 2007-2008, we analyzed epidemiologic patterns of hepatitis A in Germany and appropriateness and adequacy of current immunization recommendations. Young patients with a migration background who had visited friends and family in their ancestral countries accounted for most imported cases. Phylogenetic analysis showed high diversity of sequence data and clustering of strains with similar regions of origin or patient migration backgrounds. Virologic findings are compatible with those of low-incidence countries, where virtually all infections are directly or indirectly imported from other regions. Germans with a migration background are seen as a special risk group so far insufficiently reached by pretravel vaccination advice.

  11. Systemic fungal infections in patients with human inmunodeficiency virus.

    PubMed

    Rodríguez-Cerdeira, C; Arenas, R; Moreno-Coutiño, G; Vásquez, E; Fernández, R; Chang, P

    2014-01-01

    Histoplasmosis is a systemic infection caused by the dimorphic fungus Histoplasma capsulatum. In immunocompromised patients, primary pulmonary infection can spread to the skin and meninges. Clinical manifestations appear in patients with a CD4(+) lymphocyte count of less than 150 cells/μL. Coccidioidomycosis is a systemic mycosis caused by Coccidioides immitis and Coccidioides posadasii. It can present as diffuse pulmonary disease or as a disseminated form primarily affecting the central nervous system, the bones, and the skin. Cryptococcosis is caused by Cryptococcus neoformans (var. neoformans and var. grubii) and Cryptococcus gattii, which are members of the Cryptococcus species complex and have 5 serotypes: A, B, C, D, and AD. It is a common opportunistic infection in patients with human immunodeficiency virus (HIV)/AIDS, even those receiving antiretroviral therapy. Histopathologic examination and culture of samples from any suspicious lesions are essential for the correct diagnosis of systemic fungal infections in patients with HIV/AIDS.

  12. Prevention and management of neonatal herpes simplex virus infections.

    PubMed

    Allen, Upton D; Robinson, Joan L

    2014-04-01

    Human herpes simplex virus (HSV) infection in neonates can result in devastating outcomes, including mortality and significant morbidity. All infants are potentially at risk for neonatal HSV infection. This position statement reviews epidemiology, transmission and risk factors, with a focus on intrapartum infection. It considers diagnosis and prognosis according to infection category, along with testing modalities and limitations. Recommendations for managing newborns known to have been exposed intrapartum to HSV are based on expert opinion because a randomized trial to compare management options is not feasible. Guidance is provided for the empirical management of infants with suspected clinical sepsis, including those who do not respond to antibacterial therapy. The present statement replaces a 2006 position statement by the Canadian Paediatric Society.

  13. The influence of commensal bacteria on infection with enteric viruses

    PubMed Central

    Karst, Stephanie M.

    2016-01-01

    The intestinal microbiota exerts a marked influence in the mammalian host, both during homeostasis and disease. However, until very recently, there has been relatively little focus on the potential effect of commensal microorganisms on viral infection of the intestinal tract. In this Progress article, I review the recent advances that elucidate the mechanisms by which enteric viruses use commensal bacteria to enhance viral infectivity. These mechanisms segregate into two general categories: the direct facilitation of viral infection, including bacterial stabilization of viral particles and the facilitation of viral attachment to host target cells; and the indirect skewing of the antiviral immune response in a manner that promotes viral infection. Finally, I discuss the implications of these interactions for the development of vaccines and novel therapeutic approaches. PMID:26853118

  14. Public health issues of hepatitis C virus infection.

    PubMed

    Papatheodoridis, George; Hatzakis, Angelos

    2012-08-01

    Hepatitis C virus (HCV) is a leading cause of liver disease worldwide, as 130-170 million individuals are chronically infected and 350,000 patients die every year from HCV infection. The HCV prevalence varies widely among countries being highest in several African and Eastern Mediterranean countries. The incidence of new HCV infections may be declining in developed countries, but there is still a large reservoir of chronic infections. The most important mode of HCV transmission has been injecting drug use in developed countries with low prevalence and unsafe therapeutic injections in developing countries with moderate-high prevalence. Since there are no systematic screening policies, most patients remain undiagnosed. Even among diagnosed patients, a minority receives treatment due to several barriers to therapy. Given the high efficacy of treatment, public health authorities should recognise the importance of HCV and make resources available for the implementation of effective primary prevention, screening and management policies.

  15. The influence of commensal bacteria on infection with enteric viruses.

    PubMed

    Karst, Stephanie M

    2016-04-01

    The intestinal microbiota exerts a marked influence in the mammalian host, both during homeostasis and disease. However, until very recently, there has been relatively little focus on the potential effect of commensal microorganisms on viral infection of the intestinal tract. In this Progress article, I review the recent advances that elucidate the mechanisms by which enteric viruses use commensal bacteria to enhance viral infectivity. These mechanisms segregate into two general categories: the direct facilitation of viral infection, including bacterial stabilization of viral particles and the facilitation of viral attachment to host target cells; and the indirect skewing of the antiviral immune response in a manner that promotes viral infection. Finally, I discuss the implications of these interactions for the development of vaccines and novel therapeutic approaches.

  16. Co-infections with hepatitis B and C viruses in human immunodeficiency virus-infected patients in Morocco.

    PubMed

    Rebbani, K; Ouladlahsen, A; Bensghir, A; Akil, A; Lamdini, H; Issouf, H; Brahim, I; Kitab, B; Fakhir, F Z; Wakrim, L; Marhoum El Filali, K; Himmich, H; Ezzikouri, S; Benjelloun, S

    2013-10-01

    Human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) are major public health concerns. We aimed to determine the prevalence of HBV and HCV infections among HIV-infected patients, and to identify the main circulating hepatitis strains in Morocco. The study was carried out in 503 HIV-infected patients. Our survey indicated that the prevalence of HIV/hepatitis co-infection was 10.6%; 5.2% of patients were HBV surface antigen positive, and 5.4% of patients were anti-HCV positive. Among the HBV surface antigen-positive group, HBV DNA sequencing identified exclusively genotype D (D1: 26.7%; D7: 73.3%) in accordance with what is found in the general population. In contrast, sequencing of HCV isolates produced an unusual subtype distribution with a decreasing order of prevalence: 1a, 3a (both 23.5%), 1b, 4a (both 17.6%), 1c (11.8%) and 6h (6%).

  17. Serologic Evidence of Jamestown Canyon and Keystone Virus Infection in Vertebrates of the Delmarva Peninsula

    DTIC Science & Technology

    1982-01-01

    infected by KEY virus was isolated from female Aedes infir- JC and/or KEY viruses . N antibody prevalence matus and not from several other mosquito species... viruses also was found in raccoons, horses and humans. JC and/or KEY virus N antibodies were not demonstrable in sera of several other species of...antibodies to JC and KEY viruses . Following experimental inoculation with either JC or KEY virus , all goats developed N antibody despite the absence of a

  18. Genetic variation of occult hepatitis B virus infection

    PubMed Central

    Zhu, Hui-Lan; Li, Xu; Li, Jun; Zhang, Zhen-Hua

    2016-01-01

    Occult hepatitis B virus infection (OBI), characterized as the persistence of hepatitis B virus (HBV) surface antigen (HBsAg) seronegativity and low viral load in blood or liver, is a special form of HBV infection. OBI may be related mainly to mutations in the HBV genome, although the underlying mechanism of it remains to be clarified. Mutations especially within the immunodominant “α” determinant of S protein are “hot spots” that could contribute to the occurrence of OBI via affecting antigenicity and immunogenicity of HBsAg or replication and secretion of virion. Clinical reports account for a large proportion of previous studies on OBI, while functional analyses, especially those based on full-length HBV genome, are rare. PMID:27053845

  19. Pathology of Lassa virus infection in the rhesus monkey.

    PubMed

    Callis, R T; Jahrling, P B; DePaoli, A

    1982-09-01

    The clinical signs and gross and microscopic lesions of Lassa virus infection in the rhesus monkey are described. Of 17 monkeys infected with Lassa virus, nine died or were killed when moribund. The clinical signs were lethargy, aphagia, constipation, fever, conjunctivitis, and skin rash. Pulmonary congestion, pleural effusion, pericardial edema, hydropericardium, and a few visceral hemorrhages were present grossly. Major microscopic lesions were necrotizing hepatitis and interstitial pneumonia. Other microscopic changes were present in the heart, small intestine, spleen, lymph nodes, kidney, urinary bladder, adrenal glands, and central nervous system; however, most of these lesions were mild. In fact, death could not always be attributed to the morphologic changes; therefore, function alterations must be examined.

  20. Multiplex PCR for identification of herpes virus infections in adolescents.

    PubMed

    Durzyńska, Julia; Pacholska-Bogalska, Joanna; Kaczmarek, Maria; Hanć, Tomasz; Durda, Magdalena; Skrzypczak, Magdalena; Goździcka-Józefiak, Anna

    2011-02-01

    The aim of the study was to develop a multiplex PCR (mPCR) for a rapid and simultaneous detection of herpes simplex 1 (HSV-1), herpes simplex 2 (HSV-2), and human cytomegalovirus (HCMV) DNA in squamous oral cells obtained from adolescents. Accuracy of the method was tested in a group of 513 adolescents, almost 11% of subjects were positive for infection with herpes viruses. Correlations with gender, age, and place of residence were sought. A similar incidence of HSV-2 and HCMV was found (4.3% and 5.4%, respectively) and the incidence of HSV-1 was the lowest (1%) in the study group. Conversely to HSV-2, HCMV was detected mostly in the youngest individuals. The same occurrence of all viruses was observed in boys and girls. The mPCR method described is suggested as a useful tool for epidemiologic studies of active herpes infections.

  1. HEPATITIS VIRUS C INFECTION, ADIPOKINES AND HEPATIC STEATO–FIBROSIS

    PubMed Central

    Ciurtin, C

    2008-01-01

    Hepatitis C viral infection is accompanied by various serum alterations that could explain its molecular impact on hepatic structure and metabolic homeostasis. Recently it has been shown that adipocytokines play a pivotal role in development of hepatic steato–fibrosis, different studies giving a support of the hypothesis that the balance of adipocytokine expression is a key regulator for the progression of hepatic steatosis and fibrosis. The association between insulin resistance and hepatitis C virus genotypes and liver fibrosis stage foreshadowed that virus–induced insulin resistance may be a mechanism for fibrogenesis in chronic hepatitis C virus infection. The main importance of adipocytokine profile detection consists in the prediction of steatosis induction that has clinical relevance, being associated with advanced fibrosis and hyporesponsiveness to antiviral therapy. PMID:20108479

  2. Immunopathogenesis of Oropharyngeal Candidiasis in Human Immunodeficiency Virus Infection

    PubMed Central

    de Repentigny, Louis; Lewandowski, Daniel; Jolicoeur, Paul

    2004-01-01

    Oropharyngeal and esophageal candidiases remain significant causes of morbidity in human immunodeficiency virus (HIV)-infected patients, despite the dramatic ability of antiretroviral therapy to reconstitute immunity. Notable advances have been achieved in understanding, at the molecular level, the relationships between the progression of HIV infection, the acquisition, maintenance, and clonality of oral candidal populations, and the emergence of antifungal resistance. However, the critical immunological defects which are responsible for the onset and maintenance of mucosal candidiasis in patients with HIV infection have not been elucidated. The devastating impact of HIV infection on mucosal Langerhans' cell and CD4+ cell populations is most probably central to the pathogenesis of mucosal candidiasis in HIV-infected patients. However, these defects may be partly compensated by preserved host defense mechanisms (calprotectin, keratinocytes, CD8+ T cells, and phagocytes) which, individually or together, may limit Candida albicans proliferation to the superficial mucosa. The availability of CD4C/HIV transgenic mice expressing HIV-1 in immune cells has provided the opportunity to devise a novel model of mucosal candidiasis that closely mimics the clinical and pathological features of candidal infection in human HIV infection. These transgenic mice allow, for the first time, a precise cause-and-effect analysis of the immunopathogenesis of mucosal candidiasis in HIV infection under controlled conditions in a small laboratory animal. PMID:15489345

  3. Stability of the gorilla microbiome despite simian immunodeficiency virus infection.

    PubMed

    Moeller, Andrew H; Peeters, Martine; Ayouba, Ahidjo; Ngole, Eitel Mpoudi; Esteban, Amadine; Hahn, Beatrice H; Ochman, Howard

    2015-02-01

    Simian immunodeficiency viruses (SIVs) have been discovered in over 45 primate species; however, the pathogenic potential of most SIV strains remains unknown due to difficulties inherent in observing wild populations. Because those SIV infections that are pathogenic have been shown to induce changes in the host's gut microbiome, monitoring the microbiota present in faecal samples can provide a noninvasive means for studying the effects of SIV infection on the health of wild-living primates. Here, we examine the effects of SIVgor, a close relative of SIVcpz of chimpanzees and HIV-1 of humans, on the gut bacterial communities residing within wild gorillas, revealing that gorilla gut microbiomes are exceptionally robust to SIV infection. In contrast to the microbiomes of HIV-1-infected humans and SIVcpz-infected chimpanzees, SIVgor-infected gorilla microbiomes exhibit neither rises in the frequencies of opportunistic pathogens nor elevated rates of microbial turnover within individual hosts. Regardless of SIV infection status, gorilla microbiomes assort into enterotypes, one of which is compositionally analogous to those identified in humans and chimpanzees. The other gorilla enterotype appears specialized for a leaf-based diet and is enriched in environmentally derived bacterial genera. We hypothesize that the acquisition of this gorilla-specific enterotype was enabled by lowered immune system control over the composition of the microbiome. Our results indicate differences between the pathology of SIVgor and SIVcpz/HIV-1 infections, demonstrating the utility of investigating host microbial ecology as a means for studying disease in wild primates of high conservation priority.

  4. Respiratory syncytial virus infection increases chlorine-induced airway hyperresponsiveness

    PubMed Central

    Song, Weifeng; Yu, Zhihong; Doran, Stephen F.; Ambalavanan, Namasivayam; Steele, Chad; Garantziotis, Stavros

    2015-01-01

    Exposure to chlorine (Cl2) damages airway and alveolar epithelia resulting in acute lung injury and reactive airway hyperresponsiveness (AHR) to methacholine. However, little is known about the effect of preexisting respiratory disease on Cl2-induced lung injury. By using a murine respiratory syncytial virus (RSV) infection model, we found that preexisting RSV infection increases Cl2 (187 ppm for 30 min)-induced lung inflammation and airway AHR at 24 h after exposure (5 days after infection). RSV infection and Cl2 exposure synergistically induced oxygen desaturation and neutrophil infiltration and increased MCP-1, MIP-1β, IL-10, IFN-γ, and RANTES concentrations in the bronchoalveolar lavage fluid (BALF). In contrast, levels of type 2 cytokines (i.e., IL-4, IL-5, IL-9, and IL-13) were not significantly affected by either RSV infection or Cl2 exposure. Cl2 exposure, but not RSV infection, induced AHR to methacholine challenge as measured by flexiVent. Moreover, preexisting RSV infection amplified BALF levels of hyaluronan (HA) and AHR. The Cl2-induced AHR was mitigated by treatment with inter-α-trypsin inhibitor antibody, which inhibits HA signaling, suggesting a mechanism of HA-mediated AHR from exacerbated oxidative injury. Our results show for the first time that preexisting RSV infection predisposes the lung to Cl2-induced injury. These data emphasize the necessity for further research on the effects of Cl2 in vulnerable populations and the development of appropriate treatments. PMID:26071553

  5. Modeling Influenza Virus Infection: A Roadmap for Influenza Research

    PubMed Central

    Boianelli, Alessandro; Nguyen, Van Kinh; Ebensen, Thomas; Schulze, Kai; Wilk, Esther; Sharma, Niharika; Stegemann-Koniszewski, Sabine; Bruder, Dunja; Toapanta, Franklin R.; Guzmán, Carlos A.; Meyer-Hermann, Michael; Hernandez-Vargas, Esteban A.

    2015-01-01

    Influenza A virus (IAV) infection represents a global threat causing seasonal outbreaks and pandemics. Additionally, secondary bacterial infections, caused mainly by Streptococcus pneumoniae, are one of the main complications and responsible for the enhanced morbidity and mortality associated with IAV infections. In spite of the significant advances in our knowledge of IAV infections, holistic comprehension of the interplay between IAV and the host immune response (IR) remains largely fragmented. During the last decade, mathematical modeling has been instrumental to explain and quantify IAV dynamics. In this paper, we review not only the state of the art of mathematical models of IAV infection but also the methodologies exploited for parameter estimation. We focus on the adaptive IR control of IAV infection and the possible mechanisms that could promote a secondary bacterial coinfection. To exemplify IAV dynamics and identifiability issues, a mathematical model to explain the interactions between adaptive IR and IAV infection is considered. Furthermore, in this paper we propose a roadmap for future influenza research. The development of a mathematical modeling framework with a secondary bacterial coinfection, immunosenescence, host genetic factors and responsiveness to vaccination will be pivotal to advance IAV infection understanding and treatment optimization. PMID:26473911

  6. Detection of Zika Virus Infection in Thailand, 2012-2014.

    PubMed

    Buathong, Rome; Hermann, Laura; Thaisomboonsuk, Butsaya; Rutvisuttinunt, Wiriya; Klungthong, Chonticha; Chinnawirotpisan, Piyawan; Manasatienkij, Wudtichai; Nisalak, Ananda; Fernandez, Stefan; Yoon, In-Kyu; Akrasewi, Passakorn; Plipat, Tanarak

    2015-08-01

    Zika virus (ZIKV) is an emerging mosquito-borne pathogen with reported cases in Africa, Asia, and large outbreaks in the Pacific. No autochthonous ZIKV infections have been confirmed in Thailand. However, there have been several cases reported in travelers returning from Thailand. Here we report seven cases of acute ZIKV infection in Thai residents across the country confirmed by molecular or serological testing including sequence data. These endemic cases, combined with previous reports in travelers, provide evidence that ZIKV is widespread throughout Thailand.

  7. Neuromyelitis optica in patients with coexisting human immunodeficiency virus infections.

    PubMed

    Feyissa, Anteneh M; Singh, Parbhdeep; Smith, Robert G

    2013-09-01

    Two patients with known human immunodeficiency virus (HIV) infections and receiving antiretroviral treatment developed neuromyelitis optica (Devic's disease). One patient tested positive for serum aquaporin-4 immunoglobulin G antibodies. Both patients were treated with high dose pulsed intravenous methylprednisolone followed by standard sessions of plasma exchange both at the onset attack and during disease relapses. For maintenance therapy, one patient received rituximab infusions and the second patient received mycophenolate mofetil orally. Despite treatment, both patients are currently wheelchair-bound due to severe paraparesis. Neuromyelitis optica can occur in the course of HIV infection and poses an ongoing therapeutic challenge.

  8. Does Zika virus infection affect mosquito response to repellents?

    PubMed

    Leal, Walter S; Barbosa, Rosângela M R; Zeng, Fangfang; Faierstein, Gabriel B; Tan, Kaiming; Paiva, Marcelo H S; Guedes, Duschinka R D; Crespo, Mônica M; Ayres, Constância F J

    2017-02-16

    The World Health Organization (WHO) recommends that people travelling to or living in areas with Zika virus (ZIKV) outbreaks or epidemics adopt prophylactic measures to reduce or eliminate mosquito bites, including the use of insect repellents. It is, however, unknown whether repellents are effective against ZIKV-infected mosquitoes, in part because of the ethical concerns related to exposing a human subject's arm to infected mosquitoes in the standard arm-in-cage assay. We used a previously developed, human subject-free behavioural assay, which mimics a human subject to evaluate the top two recommended insect repellents. Our measurements showed that DEET provided significantly higher protection than picaridin provided against noninfected, host-seeking females of the southern house mosquito, Culex quinquefasciatus, and the yellow fever mosquito, Aedes aegypti. When tested at lower doses, we observed a significant reduction in DEET-elicited protection against ZIKV-infected yellow fever mosquitoes from old and recent laboratory colonies. The reduction in protection is more likely associated with aging than the virus infection and could be compensated by applying a 5x higher dose of DEET. A substantial protection against ZIKV-infected and old noninfected mosquitoes was achieved with 5% DEET, which corresponds approximately to a 30% dose in the conventional arm-in-cage assays.

  9. Hepatitis B and hepatitis delta virus infection in South America.

    PubMed Central

    Torres, J R

    1996-01-01

    About 100,000 cases of acute hepatitis B virus (HBV) infection occur annually in South America. The overall prevalence of HBV infection in low risk populations ranges from 6.7% to 41%, while hepatitis B surface antigen (HBsAg) rates range from 0.4% to 13%. In high endemicity aboriginal or rural populations, perinatal transmission may play a major part in the spread of HBV. In urban populations, however, horizontal transmission, probably by sexual contact, is the predominant mode of spread, with higher rates of HBV positivity in lower socioeconomic groups. High risk populations such as health care workers and haemodialysis patients show higher rates of HBV infection than comparable populations elsewhere. The risk of posttransfusion hepatitis B remains high in some areas. Concomitant HBV infection may accelerate the chronic liver disease seen in decompensated hepatosplenic schistosomiasis. In the north, the prevalence of hepatitis delta virus (HDV) infection ranks among the highest in the world. In the south, the problem appears negligible although it is increasing within high risk urban communities. HDV superinfection has been the cause of large outbreaks of fulminant hepatitis. The cost of comprehensive or mass vaccination programmes remains unaffordable for most South American countries. Less expensive alternatives such as low dose intradermal schedules of immunisation have been used with success in selected adult subjects. PMID:8786054

  10. Pseudorabies virus infection inhibits autophagy in permissive cells in vitro

    PubMed Central

    Sun, Mingxia; Hou, Linlin; Tang, Yan-dong; Liu, Yonggang; Wang, Shujie; Wang, Jingfei; Shen, Nan; An, Tongqing; Tian, Zhijun; Cai, Xuehui

    2017-01-01

    A large number of studies have demonstrated that autophagy is involved in the infection processes of different pathogens. Autophagy is now recognized as an essential component of innate and adaptive immunity. Several herpesviruses have developed various strategies to evade this antiviral mechanism. Pseudorabies virus (PRV) is a swine herpesvirus with a broad host range that causes devastating disease in infected pigs. In this study, we described the interaction between PRV and autophagy for the first time. PRV infection had a dual effect on the cell autophagy response; during the early period of infection, PRV virions induced autophagy without viral replication, and with viral protein expression, PRV reduced the basal level of autophagy in several permissive cells. We observed that inhibit the level of autophagy could increase the titer of infectious PRV. We also found that the conserved alphaherpesvirus US3 tegument protein may reduce the level of autophagy via