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Sample records for pathogenic virus infection

  1. 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...

  2. High doses of highly pathogenic avian influenza virus in chicken meat are required to infect ferrets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    H5N1 high pathogenicity avian influenza viruses (HPAIV) have caused natural and experimental infections in various animals through consumption of infected bird carcasses and meat. However, little is known about the quantity of virus required and if all HPAIV subtypes can cause infections following c...

  3. Pathogenic simian immunodeficiency virus infection is associated with expansion of the enteric virome.

    PubMed

    Handley, Scott A; Thackray, Larissa B; Zhao, Guoyan; Presti, Rachel; Miller, Andrew D; Droit, Lindsay; Abbink, Peter; Maxfield, Lori F; Kambal, Amal; Duan, Erning; Stanley, Kelly; Kramer, Joshua; Macri, Sheila C; Permar, Sallie R; Schmitz, Joern E; Mansfield, Keith; Brenchley, Jason M; Veazey, Ronald S; Stappenbeck, Thaddeus S; Wang, David; Barouch, Dan H; Virgin, Herbert W

    2012-10-12

    Pathogenic simian immunodeficiency virus (SIV) infection is associated with enteropathy, which likely contributes to AIDS progression. To identify candidate etiologies for AIDS enteropathy, we used next-generation sequencing to define the enteric virome during SIV infection in nonhuman primates. Pathogenic, but not nonpathogenic, SIV infection was associated with significant expansion of the enteric virome. We identified at least 32 previously undescribed enteric viruses during pathogenic SIV infection and confirmed their presence by using viral culture and PCR testing. We detected unsuspected mucosal adenovirus infection associated with enteritis as well as parvovirus viremia in animals with advanced AIDS, indicating the pathogenic potential of SIV-associated expansion of the enteric virome. No association between pathogenic SIV infection and the family-level taxonomy of enteric bacteria was detected. Thus, enteric viral infections may contribute to AIDS enteropathy and disease progression. These findings underline the importance of metagenomic analysis of the virome for understanding AIDS pathogenesis.

  4. Low pathogenicity avian influenza viruses infect chicken layers by different routes of inoculation.

    PubMed

    Pantin-Jackwood, Mary J; Smith, Diane M; Wasilenko, Jamie L; Spackman, Erica

    2012-06-01

    In order to develop better control measures against avian influenza, it is necessary to understand how the virus transmits in poultry. In a previous study in which the infectivity and transmissibility of the pandemic H1N1 influenza virus was examined in different poultry species, we found that no or minimal infection occurred in chicken and turkeys intranasally (IN) inoculated with the virus. However, we demonstrated that the virus can infect laying turkey hens by the intracloacal (IC) and intraoviduct (IO) routes, possibly explaining the drops in egg production observed in turkey breeder farms affected by the virus. Such novel routes of exposure have not been previously examined in chickens and could also explain outbreaks of low pathogenicity avian influenza (LPAI) that cause a decrease in egg production in chicken layers and breeders. In the present study, 46-wk-old specific-pathogen-free chicken layers were infected by the IN, IC, or IO routes with one of two LPAI viruses: a poultry origin virus, A/chicken/CA/1255/02 (H6N2), and a live bird market isolate, A/chicken/NJ/12220/97 (H9N2). Only hens IN inoculated with the H6N2 virus presented mild clinical signs consisting of depression and anorexia. However, a decrease in number of eggs laid was observed in all virus-inoculated groups when compared to control hens. Evidence of infection was found in all chickens inoculated with the H6N2 virus by any of the three routes and the virus transmitted to contact hens. On the other hand, only one or two hens from each of the groups inoculated with the H9N2 virus shed detectable levels of virus, or seroconverted and did not transmit the virus to contacts, regardless of the route of inoculation. In conclusion, LPAI viruses can also infect chickens through other routes besides the IN route, which is considered the natural route of exposure. However, as seen with the H9N2 virus, the infectivity of the virus did not increase when given by these alternate routes.

  5. 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...

  6. Immediate early responses of avian tracheal epithelial cells to infection with highly pathogenic avian invluenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Highly pathogenic (HP) avian influenza viruses (AIV) present an ongoing threat to the world poultry industry. In order to develop new AIV control strategies it is necessary to understand the underlying mechanism of viral infection at mucosal respiratory sites. Chicken and duck tracheal epithelial ...

  7. Effect of Infection with a Mesogenic Strain of Newcastle Disease Virus on Infection with Highly Pathogenic Avian Influenza Virus in Chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Little is known on the interactions between avian influenza virus (AIV) and Newcastle disease virus (NDV) when coinfecting the same poultry host. In a previous study we found that infection of chickens with a mesogenic strain of NDV (mNDV) can reduce highly pathogenic AIV (HPAIV) replication, clinic...

  8. 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...

  9. Experimental co-infections of domestic ducks with a virulent Newcastle disease virus and low or highly pathogenic avian influenza viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Infections with Avian influenza viruses (AIV) of low and high pathogenicity (LP and HP), and Newcastle disease virus (NDV) are commonly reported in domestic ducks in parts of the world. However, it’s not clear if co-infections with these viruses affect the severity of the diseases they produce, the ...

  10. Transcriptomic analysis reveals the potential of highly pathogenic PRRS virus to modulate immune system activation related to host-pathogen and damage associated signaling in infected porcine monocytes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    One of the largest risks to the continued stability of the swine industry is by pathogens like porcine reproductive and respiratory syndrome virus (PRRSV) that can decimate production as it spreads among individuals. These infections can be low or highly pathogenic, and because it infects monocytic ...

  11. [Serologic studies of domestic cats for potential human pathogenic virus infections from wild rodents].

    PubMed

    Nowotny, N

    1996-05-01

    For several viral infections a reservoir in wild rodents has been demonstrated. Some of the agents are known or suspected to be pathogenic for humans. Because improvements in hygiene have reduced direct human contact with rodents, domestic cats could be acting as active transmitters of these viruses from rodents to man. We selected 4 such pathogens--ortho- and parapox-, hanta- and encephalomyocarditis viruses--which, in different ways, may lead to serious human illness: Ortho- and parapoxvirus infections may cause localized pox lesions following direct skin contact. In general, the lesions heal without complications; in immunosuppressed or -deficient individuals, however, infection may generalize and take a dramatic course. Hantaviruses exist in various serotypes with different pathogenicity for human beings, varying from asymptomatic infection to highly fatal disease. In central and northern Europe the Puumala serotype is predominant causing influenza-like symptoms and renal dysfunction. Human infections arise from inhalation of aerosolized excreta of persistently infected rodents. Infections of man associated with encephalomyocarditis virus were demonstrated sporadically in cases of encephalitis and meningitis. In the present study, we investigated in 200 feline serum samples the prevalence of antibodies to ortho- and parapox-, hanta- and encephalomyocarditis virus. All serum samples were from cats that had been allowed to roam outside and to hunt. They were submitted from all parts of Austria for routine diagnosis in 1993. Four per cent of cats showed antibodies to orthopoxviruses with haemagglutination inhibition (HI) titres of 16-512; because of extensive cross-reactivity, positive samples reacted with all investigated orthopoxviruses (a feline orthopoxvirus recently isolated in Vienna, the reference strain of cowpox virus, Brighton, and vaccinia virus, strain IHD), only varying in titre. The specificity of the results was confirmed by virus neutralisation (VN

  12. AXL-dependent infection of human fetal endothelial cells distinguishes Zika virus from other pathogenic flaviviruses

    PubMed Central

    Richard, Audrey Stéphanie; Shim, Byoung-Shik; Kwon, Young-Chan; Zhang, Rong; Otsuka, Yuka; Schmitt, Kimberly; Berri, Fatma; Diamond, Michael S.; Choe, Hyeryun

    2017-01-01

    Although a causal relationship between Zika virus (ZIKV) and microcephaly has been established, it remains unclear why ZIKV, but not other pathogenic flaviviruses, causes congenital defects. Here we show that when viruses are produced in mammalian cells, ZIKV, but not the closely related dengue virus (DENV) or West Nile virus (WNV), can efficiently infect key placental barrier cells that directly contact the fetal bloodstream. We show that AXL, a receptor tyrosine kinase, is the primary ZIKV entry cofactor on human umbilical vein endothelial cells (HUVECs), and that ZIKV uses AXL with much greater efficiency than does DENV or WNV. Consistent with this observation, only ZIKV, but not WNV or DENV, bound the AXL ligand Gas6. In comparison, when DENV and WNV were produced in insect cells, they also infected HUVECs in an AXL-dependent manner. Our data suggest that ZIKV, when produced from mammalian cells, infects fetal endothelial cells much more efficiently than other pathogenic flaviviruses because it binds Gas6 more avidly, which in turn facilitates its interaction with AXL. PMID:28167751

  13. AXL-dependent infection of human fetal endothelial cells distinguishes Zika virus from other pathogenic flaviviruses.

    PubMed

    Richard, Audrey Stéphanie; Shim, Byoung-Shik; Kwon, Young-Chan; Zhang, Rong; Otsuka, Yuka; Schmitt, Kimberly; Berri, Fatma; Diamond, Michael S; Choe, Hyeryun

    2017-02-21

    Although a causal relationship between Zika virus (ZIKV) and microcephaly has been established, it remains unclear why ZIKV, but not other pathogenic flaviviruses, causes congenital defects. Here we show that when viruses are produced in mammalian cells, ZIKV, but not the closely related dengue virus (DENV) or West Nile virus (WNV), can efficiently infect key placental barrier cells that directly contact the fetal bloodstream. We show that AXL, a receptor tyrosine kinase, is the primary ZIKV entry cofactor on human umbilical vein endothelial cells (HUVECs), and that ZIKV uses AXL with much greater efficiency than does DENV or WNV. Consistent with this observation, only ZIKV, but not WNV or DENV, bound the AXL ligand Gas6. In comparison, when DENV and WNV were produced in insect cells, they also infected HUVECs in an AXL-dependent manner. Our data suggest that ZIKV, when produced from mammalian cells, infects fetal endothelial cells much more efficiently than other pathogenic flaviviruses because it binds Gas6 more avidly, which in turn facilitates its interaction with AXL.

  14. Viruses accumulate in aging infection centers of a fungal forest pathogen

    PubMed Central

    Vainio, Eeva J; Müller, Michael M; Korhonen, Kari; Piri, Tuula; Hantula, Jarkko

    2015-01-01

    Fungal viruses (mycoviruses) with RNA genomes are believed to lack extracellular infective particles. These viruses are transmitted laterally among fungal strains through mycelial anastomoses or vertically via their infected spores, but little is known regarding their prevalence and patterns of dispersal under natural conditions. Here, we examined, in detail, the spatial and temporal changes in a mycovirus community and its host fungus Heterobasidion parviporum, the most devastating fungal pathogen of conifers in the Boreal forest region. During the 7-year sampling period, viruses accumulated in clonal host individuals as a result of indigenous viruses spreading within and between clones as well as novel strains arriving via airborne spores. Viral community changes produced pockets of heterogeneity within large H. parviporum clones. The appearance of novel viral infections in aging clones indicated that transient cell-to-cell contacts between Heterobasidion strains are likely to occur more frequently than what was inferred from genotypic analyses. Intraspecific variation was low among the three partitivirus species at the study site, whereas the unassigned viral species HetRV6 was highly polymorphic. The accumulation of point mutations during persistent infections resulted in viral diversification, that is, the presence of nearly identical viral sequence variants within single clones. Our results also suggest that co-infections by distantly related viral species are more stable than those between conspecific strains, and mutual exclusion may play a role in determining mycoviral communities. PMID:25126757

  15. Adaptive Heterosubtypic Immunity to Low Pathogenic Avian Influenza Viruses in Experimentally Infected Mallards

    PubMed Central

    Segovia, Karen M.; Stallknecht, David E.; Kapczynski, Darrell R.; Stabler, Lisa; Berghaus, Roy D.; Fotjik, Alinde; Latorre-Margalef, Neus; França, Monique S.

    2017-01-01

    Mallards are widely recognized as reservoirs for Influenza A viruses (IAV); however, host factors that might prompt seasonality and trends in subtype diversity of IAV such as adaptive heterosubtypic immunity (HSI) are not well understood. To investigate this, we inoculated mallards with a prevailing H3N8 low pathogenic avian influenza virus (LPAIV) subtype in waterfowl to determine if prior infection with this virus would be protective against heterosubtypic infections with the H4N6, H10N7 and H14N5 LPAIV subtypes after one, two and three months, respectively. Also, we investigated the effect of cumulative immunity after sequential inoculation of mallards with these viruses in one-month intervals. Humoral immunity was assessed by microneutralization assays using a subset of representative LPAIV subtypes as antigens. Our results indicate that prior inoculation with the H3N8 virus confers partial protective immunity against subsequent heterosubtypic infections with the robustness of HSI related to the phylogenetic similarity of the HA protein of the strains used. Furthermore, induced HSI was boosted and followed by repeated exposure to more than one LPAIV subtype. Our findings provide further information on the contributions of HSI and its role in the dynamics of IAV subtype diversity in mallards. PMID:28107403

  16. Host immune responses of ducks infected with H5N1 highly pathogenic avian influenza viruses of different pathogenicities.

    PubMed

    Wei, Liangmeng; Jiao, Peirong; Song, Yafen; Cao, Lan; Yuan, Runyu; Gong, Lang; Cui, Jin; Zhang, Shuo; Qi, Wenbao; Yang, Su; Liao, Ming

    2013-10-25

    Our previous studies have illustrated three strains of duck-origin H5N1 highly pathogenic avian influenza viruses (HPAIVs) had varying levels of pathogenicity in ducks (Sun et al., 2011). However, the host immune response of ducks infected with those of H5N1 HPAIVs was unclear. Here, we compared viral distribution and mRNA expression of immune-related genes in ducks following infection with the two HPAIV (A/Duck/Guangdong/212/2004, DK212 and A/Duck/Guangdong/383/2008, DK383). DK383 could replicate in the tested tissue of ducks (brain, spleen, lungs, cloacal bursa, kidney, and pancreas) more rapid and efficiently than DK212 at 1 and 2 days post-inoculation. Quantitative real-time PCR analysis showed that the expression levels of TLR3, IL-6, IL-8, and MHC class II in brains were higher than those of respective genes in lungs during the early stage of post infection. Furthermore, the expression levels of IL-6 and IL-8 in the brain of ducks following infection with DK383 were remarkably higher than those of ducks infected with DK212, respectively. Our results suggest that the shift in the H5N1 HPAIVs to increased virulence in ducks may be associated with efficient and rapid replication of the virus, accompanied by early destruction of host immune responses. These data are helpful to understand the underlying mechanism of the different outcome of H5N1 HPAIVs infection in ducks.

  17. Human infection with highly pathogenic H5N1 influenza virus.

    PubMed

    Gambotto, Andrea; Barratt-Boyes, Simon M; de Jong, Menno D; Neumann, Gabriele; Kawaoka, Yoshihiro

    2008-04-26

    Highly pathogenic H5N1 influenza A viruses have spread relentlessly across the globe since 2003, and they are associated with widespread death in poultry, substantial economic loss to farmers, and reported infections of more than 300 people with a mortality rate of 60%. The high pathogenicity of H5N1 influenza viruses and their capacity for transmission from birds to human beings has raised worldwide concern about an impending human influenza pandemic similar to the notorious H1N1 Spanish influenza of 1918. Since many aspects of H5N1 influenza research are rapidly evolving, we aim in this Seminar to provide an up-to-date discussion on select topics of interest to influenza clinicians and researchers. We summarise the clinical features and diagnosis of infection and present therapeutic options for H5N1 infection of people. We also discuss ideas relating to virus transmission, host restriction, and pathogenesis. Finally, we discuss vaccine development in view of the probable importance of vaccination in pandemic control.

  18. Recent insights into host-pathogen interaction in white spot syndrome virus infected penaeid shrimp.

    PubMed

    Shekhar, M S; Ponniah, A G

    2015-07-01

    Viral disease outbreaks are a major concern impeding the development of the shrimp aquaculture industry. The viral disease due to white spot syndrome virus (WSSV) observed in early 1990s still continues unabated affecting the shrimp farms and cause huge economic loss to the shrimp aquaculture industry. In the absence of effective therapeutics to control WSSV, it is important to understand viral pathogenesis and shrimp response to WSSV at the molecular level. Identification and molecular characterization of WSSV proteins and receptors may facilitate in designing and development of novel therapeutics and antiviral drugs that may inhibit viral replication. Investigations into host-pathogen interactions might give new insights to viral infectivity, tissue tropism and defence mechanism elicited in response to WSSV infection. However, due to the limited information on WSSV gene function and host immune response, the signalling pathways which are associated in shrimp pathogen interaction have also not been elucidated completely. In the present review, the focus is on those shrimp proteins and receptors that are potentially involved in virus infection or in the defence mechanism against WSSV. In addition, the major signalling pathways involved in the innate immune response and the role of apoptosis in host-pathogen interaction is discussed.

  19. Cytokine response in mouse bone marrow derived macrophages after infection with pathogenic and non-pathogenic Rift Valley fever virus.

    PubMed

    Roberts, Kimberly K; Hill, Terence E; Davis, Melissa N; Holbrook, Michael R; Freiberg, Alexander N

    2015-07-01

    Rift Valley fever virus (RVFV) is the most pathogenic member of the genus Phlebovirus within the family Bunyaviridae, and can cause severe disease in humans and livestock. Until recently, limited information has been published on the cellular host response elicited by RVFV, particularly in macrophages and dendritic cells, which play critical roles in stimulating adaptive and innate immune responses to viral infection. In an effort to define the initial response of host immunomodulatory cells to infection, primary mouse bone marrow derived macrophages (BMDM) were infected with the pathogenic RVFV strain ZH501, or attenuated strains MP-12 or MP-12 based Clone13 type (rMP12-C13 type), and cytokine secretion profiles examined. The secretion of T helper (Th)1-associated antiviral cytokines, chemokines and various interleukins increased rapidly after infection with the attenuated rMP12-C13 type RVFV, which lacks a functional NSs virulence gene. In comparison, infection with live-attenuated MP-12 encoding a functional NSs gene appeared to cause a delayed immune response, while pathogenic ZH501 ablates the immune response almost entirely. These data demonstrate that NSs can inhibit components of the BMDM antiviral response and supports previous work indicating that NSs can specifically regulate the type I interferon response in macrophages. Furthermore, our data demonstrate that genetic differences between ZH501 and MP-12 reduce the ability of MP-12 to inhibit antiviral signalling and subsequently reduce virulence in BMDM, demonstrating that viral components other than NSs play a critical role in regulating the host response to RVFV infection.

  20. Cytokine response in mouse bone marrow derived macrophages after infection with pathogenic and non-pathogenic Rift Valley fever virus

    PubMed Central

    Roberts, Kimberly K.; Hill, Terence E.; Davis, Melissa N.; Holbrook, Michael R.

    2015-01-01

    Rift Valley fever virus (RVFV) is the most pathogenic member of the genus Phlebovirus within the family Bunyaviridae, and can cause severe disease in humans and livestock. Until recently, limited information has been published on the cellular host response elicited by RVFV, particularly in macrophages and dendritic cells, which play critical roles in stimulating adaptive and innate immune responses to viral infection. In an effort to define the initial response of host immunomodulatory cells to infection, primary mouse bone marrow derived macrophages (BMDM) were infected with the pathogenic RVFV strain ZH501, or attenuated strains MP-12 or MP-12 based Clone13 type (rMP12-C13 type), and cytokine secretion profiles examined. The secretion of T helper (Th)1-associated antiviral cytokines, chemokines and various interleukins increased rapidly after infection with the attenuated rMP12-C13 type RVFV, which lacks a functional NSs virulence gene. In comparison, infection with live-attenuated MP-12 encoding a functional NSs gene appeared to cause a delayed immune response, while pathogenic ZH501 ablates the immune response almost entirely. These data demonstrate that NSs can inhibit components of the BMDM antiviral response and supports previous work indicating that NSs can specifically regulate the type I interferon response in macrophages. Furthermore, our data demonstrate that genetic differences between ZH501 and MP-12 reduce the ability of MP-12 to inhibit antiviral signalling and subsequently reduce virulence in BMDM, demonstrating that viral components other than NSs play a critical role in regulating the host response to RVFV infection. PMID:25759029

  1. Divergent CD4+ T memory stem cell dynamics in pathogenic and nonpathogenic simian immunodeficiency virus infections.

    PubMed

    Cartwright, Emily K; McGary, Colleen S; Cervasi, Barbara; Micci, Luca; Lawson, Benton; Elliott, Sarah T C; Collman, Ronald G; Bosinger, Steven E; Paiardini, Mirko; Vanderford, Thomas H; Chahroudi, Ann; Silvestri, Guido

    2014-05-15

    Recent studies have identified a subset of memory T cells with stem cell-like properties (T(SCM)) that include increased longevity and proliferative potential. In this study, we examined the dynamics of CD4(+) T(SCM) during pathogenic SIV infection of rhesus macaques (RM) and nonpathogenic SIV infection of sooty mangabeys (SM). Whereas SIV-infected RM show selective numeric preservation of CD4(+) T(SCM), SIV infection induced a complex perturbation of these cells defined by depletion of CD4(+)CCR5(+) T(SCM), increased rates of CD4(+) T(SCM) proliferation, and high levels of direct virus infection. The increased rates of CD4(+) T(SCM) proliferation in SIV-infected RM correlated inversely with the levels of central memory CD4(+) T cells. In contrast, nonpathogenic SIV infection of SM evidenced preservation of both CD4(+) T(SCM) and CD4(+) central memory T cells, with normal levels of CD4(+) T(SCM) proliferation, and lack of selective depletion of CD4(+)CCR5(+) T(SCM). Importantly, SIV DNA was below the detectable limit in CD4(+) T(SCM) from 8 of 10 SIV-infected SM. We propose that increased proliferation and infection of CD4(+) T(SCM) may contribute to the pathogenesis of SIV infection in RM.

  2. Virus interference between H7N2 low pathogenic avian influenza virus and lentogenic Newcastle disease virus in experimental co-infections in chickens and turkeys.

    PubMed

    Costa-Hurtado, Mar; Afonso, Claudio L; Miller, Patti J; Spackman, Erica; Kapczynski, Darrell R; Swayne, David E; Shepherd, Eric; Smith, Diane; Zsak, Aniko; Pantin-Jackwood, Mary

    2014-01-06

    Low pathogenicity avian influenza virus (LPAIV) and lentogenic Newcastle disease virus (lNDV) are commonly reported causes of respiratory disease in poultry worldwide with similar clinical and pathobiological presentation. Co-infections do occur but are not easily detected, and the impact of co-infections on pathobiology is unknown. In this study chickens and turkeys were infected with a lNDV vaccine strain (LaSota) and a H7N2 LPAIV (A/turkey/VA/SEP-67/2002) simultaneously or sequentially three days apart. No clinical signs were observed in chickens co-infected with the lNDV and LPAIV or in chickens infected with the viruses individually. However, the pattern of virus shed was different with co-infected chickens, which excreted lower titers of lNDV and LPAIV at 2 and 3 days post inoculation (dpi) and higher titers at subsequent time points. All turkeys inoculated with the LPAIV, whether or not they were exposed to lNDV, presented mild clinical signs. Co-infection effects were more pronounced in turkeys than in chickens with reduction in the number of birds shedding virus and in virus titers, especially when LPAIV was followed by lNDV. In conclusion, co-infection of chickens or turkeys with lNDV and LPAIV affected the replication dynamics of these viruses but did not affect clinical signs. The effect on virus replication was different depending on the species and on the time of infection. These results suggest that infection with a heterologous virus may result in temporary competition for cell receptors or competent cells for replication, most likely interferon-mediated, which decreases with time.

  3. Sequence of Pathogenic Events in Cynomolgus Macaques Infected with Aerosolized Monkeypox Virus

    PubMed Central

    Hall, G.; Pearson, G.; Rayner, E.; Graham, V. A.; Steeds, K.; Bewley, K. R.; Hatch, G. J.; Dennis, M.; Taylor, I.; Roberts, A. D.; Funnell, S. G. P.; Vipond, J.

    2015-01-01

    ABSTRACT To evaluate new vaccines when human efficacy studies are not possible, the FDA's “Animal Rule” requires well-characterized models of infection. Thus, in the present study, the early pathogenic events of monkeypox infection in nonhuman primates, a surrogate for variola virus infection, were characterized. Cynomolgus macaques were exposed to aerosolized monkeypox virus (105 PFU). Clinical observations, viral loads, immune responses, and pathological changes were examined on days 2, 4, 6, 8, 10, and 12 postchallenge. Viral DNA (vDNA) was detected in the lungs on day 2 postchallenge, and viral antigen was detected, by immunostaining, in the epithelium of bronchi, bronchioles, and alveolar walls. Lesions comprised rare foci of dysplastic and sloughed cells in respiratory bronchioles. By day 4, vDNA was detected in the throat, tonsil, and spleen, and monkeypox antigen was detected in the lung, hilar and submandibular lymph nodes, spleen, and colon. Lung lesions comprised focal epithelial necrosis and inflammation. Body temperature peaked on day 6, pox lesions appeared on the skin, and lesions, with positive immunostaining, were present in the lung, tonsil, spleen, lymph nodes, and colon. By day 8, vDNA was present in 9/13 tissues. Blood concentrations of interleukin 1ra (IL-1ra), IL-6, and gamma interferon (IFN-γ) increased markedly. By day 10, circulating IgG antibody concentrations increased, and on day 12, animals showed early signs of recovery. These results define early events occurring in an inhalational macaque monkeypox infection model, supporting its use as a surrogate model for human smallpox. IMPORTANCE Bioterrorism poses a major threat to public health, as the deliberate release of infectious agents, such smallpox or a related virus, monkeypox, would have catastrophic consequences. The development and testing of new medical countermeasures, e.g., vaccines, are thus priorities; however, tests for efficacy in humans cannot be performed because it

  4. Toll-like receptor pre-stimulation protects mice against lethal infection with highly pathogenic influenza viruses.

    PubMed

    Shinya, Kyoko; Okamura, Tadashi; Sueta, Setsuko; Kasai, Noriyuki; Tanaka, Motoko; Ginting, Teridah E; Makino, Akiko; Eisfeld, Amie J; Kawaoka, Yoshihiro

    2011-03-04

    Since the beginning of the 20th century, humans have experienced four influenza pandemics, including the devastating 1918 'Spanish influenza'. Moreover, H5N1 highly pathogenic avian influenza (HPAI) viruses are currently spreading worldwide, although they are not yet efficiently transmitted among humans. While the threat of a global pandemic involving a highly pathogenic influenza virus strain looms large, our mechanisms to address such a catastrophe remain limited. Here, we show that pre-stimulation of Toll-like receptors (TLRs) 2 and 4 increased resistance against influenza viruses known to induce high pathogenicity in animal models. Our data emphasize the complexity of the host response against different influenza viruses, and suggest that TLR agonists might be utilized to protect against lethality associated with highly pathogenic influenza virus infection in humans.

  5. The nonstructural proteins of Nipah virus play a key role in pathogenicity in experimentally infected animals.

    PubMed

    Yoneda, Misako; Guillaume, Vanessa; Sato, Hiroki; Fujita, Kentaro; Georges-Courbot, Marie-Claude; Ikeda, Fusako; Omi, Mio; Muto-Terao, Yuri; Wild, T Fabian; Kai, Chieko

    2010-09-15

    Nipah virus (NiV) P gene encodes P protein and three accessory proteins (V, C and W). It has been reported that all four P gene products have IFN antagonist activity when the proteins were transiently expressed. However, the role of those accessory proteins in natural infection with NiV remains unknown. We generated recombinant NiVs lacking V, C or W protein, rNiV(V-), rNiV(C-), and rNiV(W-), respectively, to analyze the functions of these proteins in infected cells and the implications in in vivo pathogenicity. All the recombinants grew well in cell culture, although the maximum titers of rNiV(V-) and rNiV(C-) were lower than the other recombinants. The rNiV(V-), rNiV(C-) and rNiV(W-) suppressed the IFN response as well as the parental rNiV, thereby indicating that the lack of each accessory protein does not significantly affect the inhibition of IFN signaling in infected cells. In experimentally infected golden hamsters, rNiV(V-) and rNiV(C-) but not the rNiV(W-) virus showed a significant reduction in virulence. These results suggest that V and C proteins play key roles in NiV pathogenicity, and the roles are independent of their IFN-antagonist activity. This is the first report that identifies the molecular determinants of NiV in pathogenicity in vivo.

  6. Pathogenicity of Highly Pathogenic Avian Influenza Virus H5N1 in Naturally Infected Poultry in Egypt

    PubMed Central

    Hagag, Ibrahim Thabet; Mansour, Shimaa M. G.; Zhang, Zerui; Ali, Ahmed A. H.; Ismaiel, El-Bakry M.; Salama, Ali A.; Cardona, Carol J.; Collins, James; Xing, Zheng

    2015-01-01

    Highly pathogenic avian influenza virus (HPAIV) H5N1 has been endemic in Egypt since 2006, and there is increasing concern for its potential to become highly transmissible among humans. Infection by HPAIV H5N1 has been described in experimentally challenged birds. However, the pathogenicity of the H5N1 isolated in Egypt has never been reported in naturally infected chickens and ducks. Here we report a 2013 outbreak of HPAIV H5N1 in commercial poultry farms and backyards in Sharkia Province, Egypt. The main symptoms were ecchymosis on the shanks and feet, cyanosis of the comb and wattles, subcutaneous edema of the head and neck for chickens, and nervous signs (torticollis) for ducks. Within 48-72 hrs of the onset of illness, the average mortality rates were 22.8-30% and 28.5-40% in vaccinated chickens and non-vaccinated ducks, respectively. Tissue samples of chickens and ducks were collected for analyses with cross-section immunohistochemistry and real-time RT-PCR for specific viral RNA transcripts. While viral RNA was detected in nearly all tissues and sera collected, viral nucleoprotein was detected almost ubiquitously in all tissues, including testis. Interestingly, viral antigen was also observed in endothelial cells of most organs in chickens, and clearly detected in the trachea and brain in particular. Viral nucleoprotein was also detected in mononuclear cells of various organs, especially pulmonary tissue. We performed phylogenetic analyses and compared the genomic sequences of the hemagglutinin (HA) and nonstructural proteins (NS) among the isolated viruses, the HPAIV circulated in Egypt in the past and currently, and some available vaccine strains. Further analysis of deduced amino acids of both HA and NS1 revealed that our isolates carried molecular determinants of HPAIV, including the multibasic amino acids (PQGERRRK/KR*GLF) in the cleavage site in HA and glutamate at position 92 (D92E) in NS1. This is the first report of the pathogenicity of the HPAIVH5N

  7. Pathogenicity of Highly Pathogenic Avian Influenza Virus H5N1 in Naturally Infected Poultry in Egypt.

    PubMed

    Hagag, Ibrahim Thabet; Mansour, Shimaa M G; Zhang, Zerui; Ali, Ahmed A H; Ismaiel, El-Bakry M; Salama, Ali A; Cardona, Carol J; Collins, James; Xing, Zheng

    2015-01-01

    Highly pathogenic avian influenza virus (HPAIV) H5N1 has been endemic in Egypt since 2006, and there is increasing concern for its potential to become highly transmissible among humans. Infection by HPAIV H5N1 has been described in experimentally challenged birds. However, the pathogenicity of the H5N1 isolated in Egypt has never been reported in naturally infected chickens and ducks. Here we report a 2013 outbreak of HPAIV H5N1 in commercial poultry farms and backyards in Sharkia Province, Egypt. The main symptoms were ecchymosis on the shanks and feet, cyanosis of the comb and wattles, subcutaneous edema of the head and neck for chickens, and nervous signs (torticollis) for ducks. Within 48-72 hrs of the onset of illness, the average mortality rates were 22.8-30% and 28.5-40% in vaccinated chickens and non-vaccinated ducks, respectively. Tissue samples of chickens and ducks were collected for analyses with cross-section immunohistochemistry and real-time RT-PCR for specific viral RNA transcripts. While viral RNA was detected in nearly all tissues and sera collected, viral nucleoprotein was detected almost ubiquitously in all tissues, including testis. Interestingly, viral antigen was also observed in endothelial cells of most organs in chickens, and clearly detected in the trachea and brain in particular. Viral nucleoprotein was also detected in mononuclear cells of various organs, especially pulmonary tissue. We performed phylogenetic analyses and compared the genomic sequences of the hemagglutinin (HA) and nonstructural proteins (NS) among the isolated viruses, the HPAIV circulated in Egypt in the past and currently, and some available vaccine strains. Further analysis of deduced amino acids of both HA and NS1 revealed that our isolates carried molecular determinants of HPAIV, including the multibasic amino acids (PQGERRRK/KR*GLF) in the cleavage site in HA and glutamate at position 92 (D92E) in NS1. This is the first report of the pathogenicity of the HPAIVH5N

  8. Three-Dimensional Structure of a Protozoal Double-Stranded RNA Virus That Infects the Enteric Pathogen Giardia lamblia

    PubMed Central

    Janssen, Mandy E. W.; Takagi, Yuko; Parent, Kristin N.; Cardone, Giovanni

    2014-01-01

    ABSTRACT Giardia lamblia virus (GLV) is a small, nonenveloped, nonsegmented double-stranded RNA (dsRNA) virus infecting Giardia lamblia, the most common protozoan pathogen of the human intestine and a major agent of waterborne diarrheal disease worldwide. GLV (genus Giardiavirus) is a member of family Totiviridae, along with several other groups of protozoal or fungal viruses, including Leishmania RNA viruses and Trichomonas vaginalis viruses. Interestingly, GLV is more closely related than other Totiviridae members to a group of recently discovered metazoan viruses that includes penaeid shrimp infectious myonecrosis virus (IMNV). Moreover, GLV is the only known protozoal dsRNA virus that can transmit efficiently by extracellular means, also like IMNV. In this study, we used transmission electron cryomicroscopy and icosahedral image reconstruction to examine the GLV virion at an estimated resolution of 6.0 Å. Its outermost diameter is 485 Å, making it the largest totivirus capsid analyzed to date. Structural comparisons of GLV and other totiviruses highlighted a related “T=2” capsid organization and a conserved helix-rich fold in the capsid subunits. In agreement with its unique capacity as a protozoal dsRNA virus to survive and transmit through extracellular environments, GLV was found to be more thermoresistant than Trichomonas vaginalis virus 1, but no specific protein machinery to mediate cell entry, such as the fiber complexes in IMNV, could be localized. These and other structural and biochemical findings provide a basis for future work to dissect the cell entry mechanism of GLV into a “primitive” (early-branching) eukaryotic host and an important enteric pathogen of humans. IMPORTANCE Numerous pathogenic bacteria, including Corynebacterium diphtheriae, Salmonella enterica, and Vibrio cholerae, are infected with lysogenic bacteriophages that contribute significantly to bacterial virulence. In line with this phenomenon, several pathogenic protozoa

  9. Susceptibility And Adaptation Of A Mallard H5N2 Low Pathogenic Influenza Virus In Chickens Infected With Infectious Bursal Disease Virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The influenza A/Mallard/Pennsylvania/12180/1984 (H5N2) virus is unable to replicate in 2 to 4-week old normal, immunocompetent specific-pathogen-free (SPF) chickens. In contrast, this mallard virus shows limited replication in chickens that had been previously infected with the immunosuppressive age...

  10. Infectivity and pathogenicity of Newcastle disease virus strains of different avian origin and different virulence for mallard ducklings.

    PubMed

    Dai, Yabin; Liu, Mei; Cheng, Xu; Shen, Xinyue; Wei, Yuyong; Zhou, Sheng; Yu, Shengqing; Ding, Chan

    2013-03-01

    Experimental infections of Newcastle disease virus (NDV) strains of different avian origin and different virulence in mallard (Anas platyrhynchos) ducklings were undertaken to evaluate infectivity and pathogenicity of NDV for ducks and the potential role of ducks in the epidemiology of Newcastle disease (ND). Ducklings were experimentally infected with seven NDV strains, and their clinical sign, weight gain, antibody response, virus shedding, and virus distribution in tissues were investigated. The duck origin virulent strain duck/Jiangsu/JSD0812/2008 (JSD0812) and the Chinese standard virulent strain F48E8 were highly pathogenic for ducklings. They caused high morbidity and mortality, and they distributed extensively in various tissues of infected ducklings. Other strains, including pigeon origin virulent strain pigeon/Jiangsu/JSP0204/2002 (JSP0204), chicken origin virulent strain chicken/Jiangsu/JSC0804/2008 (JSC0804), goose origin virulent goose/Jiangsu/JSG0210/2002 (JSG0210), and vaccine strains Mukteswar and LaSota had no pathogenicity to ducklings. They produced neither clinical signs of the disease nor adverse effect on growth of infected ducklings, and they persisted in duck bodies for only a short period. Virus shedding was detectable in all infected ducklings, but its period and route varied with the virulence of NDV strains. The results suggest that NDV with high pathogenicity in ducks may arise from the evolution within its corresponding host, further confirming that the ducks play an important role in the epidemiology of ND.

  11. Evidence of infection by H5N2 highly pathogenic avian influenza viruses in healthy wild waterfowl

    USGS Publications Warehouse

    Gaidet, N.; Cattoli, G.; Hammoumi, S.; Newman, S.H.; Hagemeijer, W.; Takekawa, J.Y.; Cappelle, J.; Dodman, T.; Joannis, T.; Gil, P.; Monne, I.; Fusaro, A.; Capua, I.; Manu, S.; Micheloni, P.; Ottosson, U.; Mshelbwala, J.H.; Lubroth, J.; Domenech, J.; Monicat, F.

    2008-01-01

    The potential existence of a wild bird reservoir for highly pathogenic avian influenza (HPAI) has been recently questioned by the spread and the persisting circulation of H5N1 HPAI viruses, responsible for concurrent outbreaks in migratory and domestic birds over Asia, Europe, and Africa. During a large-scale surveillance programme over Eastern Europe, the Middle East, and Africa, we detected avian influenza viruses of H5N2 subtype with a highly pathogenic (HP) viral genotype in healthy birds of two wild waterfowl species sampled in Nigeria. We monitored the survival and regional movements of one of the infected birds through satellite telemetry, providing a rare evidence of a non-lethal natural infection by an HP viral genotype in wild birds. Phylogenetic analysis of the H5N2 viruses revealed close genetic relationships with H5 viruses of low pathogenicity circulating in Eurasian wild and domestic ducks. In addition, genetic analysis did not reveal known gallinaceous poultry adaptive mutations, suggesting that the emergence of HP strains could have taken place in either wild or domestic ducks or in non-gallinaceous species. The presence of coexisting but genetically distinguishable avian influenza viruses with an HP viral genotype in two cohabiting species of wild waterfowl, with evidence of non-lethal infection at least in one species and without evidence of prior extensive circulation of the virus in domestic poultry, suggest that some strains with a potential high pathogenicity for poultry could be maintained in a community of wild waterfowl.

  12. Early and sustained innate immune response defines pathology and death in nonhuman primates infected by highly pathogenic influenza virus

    PubMed Central

    Baskin, Carole R.; Bielefeldt-Ohmann, Helle; Tumpey, Terrence M.; Sabourin, Patrick J.; Long, James P.; García-Sastre, Adolfo; Tolnay, Airn-E.; Albrecht, Randy; Pyles, John A.; Olson, Pam H.; Aicher, Lauri D.; Rosenzweig, Elizabeth R.; Murali-Krishna, Kaja; Clark, Edward A.; Kotur, Mark S.; Fornek, Jamie L.; Proll, Sean; Palermo, Robert E.; Sabourin, Carol L.; Katze, Michael G.

    2009-01-01

    The mechanisms responsible for the virulence of the highly pathogenic avian influenza (HPAI) and of the 1918 pandemic influenza virus in humans remain poorly understood. To identify crucial components of the early host response during these infections by using both conventional and functional genomics tools, we studied 34 cynomolgus macaques (Macaca fascicularis) to compare a 2004 human H5N1 Vietnam isolate with 2 reassortant viruses possessing the 1918 hemagglutinin (HA) and neuraminidase (NA) surface proteins, known conveyors of virulence. One of the reassortants also contained the 1918 nonstructural (NS1) protein, an inhibitor of the host interferon response. Among these viruses, HPAI H5N1 was the most virulent. Within 24 h, the H5N1 virus produced severe bronchiolar and alveolar lesions. Notably, the H5N1 virus targeted type II pneumocytes throughout the 7-day infection, and induced the most dramatic and sustained expression of type I interferons and inflammatory and innate immune genes, as measured by genomic and protein assays. The H5N1 infection also resulted in prolonged margination of circulating T lymphocytes and notable apoptosis of activated dendritic cells in the lungs and draining lymph nodes early during infection. While both 1918 reassortant viruses also were highly pathogenic, the H5N1 virus was exceptional for the extent of tissue damage, cytokinemia, and interference with immune regulatory mechanisms, which may help explain the extreme virulence of HPAI viruses in humans. PMID:19218453

  13. In vitro and in vivo infectivity and pathogenicity of the lymphoid cell-derived woodchuck hepatitis virus.

    PubMed

    Lew, Y Y; Michalak, T I

    2001-02-01

    Woodchuck hepatitis virus (WHV) and human hepatitis B virus are closely related, highly hepatotropic mammalian DNA viruses that also replicate in the lymphatic system. The infectivity and pathogenicity of hepadnaviruses propagating in lymphoid cells are under debate. In this study, hepato- and lymphotropism of WHV produced by naturally infected lymphoid cells was examined in specifically established woodchuck hepatocyte and lymphoid cell cultures and coculture systems, and virus pathogenicity was tested in susceptible animals. Applying PCR-based assays discriminating between the total pool of WHV genomes and covalently closed circular DNA (cccDNA), combined with enzymatic elimination of extracellular viral sequences potentially associated with the cell surface, our study documents that virus replicating in woodchuck lymphoid cells is infectious to homologous hepatocytes and lymphoid cells in vitro. The productive replication of WHV from lymphoid cells in cultured hepatocytes was evidenced by the appearance of virus-specific DNA, cccDNA, and antigens, transmissibility of the virus through multiple passages in hepatocyte cultures, and the ability of the passaged virus to infect virus-naive animals. The data also revealed that WHV from lymphoid cells can initiate classical acute viral hepatitis in susceptible animals, albeit small quantities (approximately 10(3) virions) caused immunovirologically undetectable (occult) WHV infection that engaged the lymphatic system but not the liver. Our results provide direct in vitro and in vivo evidence that lymphoid cells in the infected host support propagation of infectious hepadnavirus that has the potential to induce hepatitis. They also emphasize a principal role of the lymphatic system in the maintenance and dissemination of hepadnavirus infection, particularly when infection is induced by low virus doses.

  14. Genetic characterization of highly pathogenic avian influenza H5N1 viruses isolated from naturally infected pigeons in Egypt.

    PubMed

    Elgendy, Emad Mohamed; Watanabe, Yohei; Daidoji, Tomo; Arai, Yasuha; Ikuta, Kazuyoshi; Ibrahim, Madiha Salah; Nakaya, Takaaki

    2016-12-01

    Avian influenza viruses impose serious public health burdens with significant mortality and morbidity not only in poultry but also in humans. While poultry susceptibility to avian influenza virus infection is well characterized, pigeons have been thought to have low susceptibility to these viruses. However, recent studies reported natural pigeon infections with highly pathogenic avian influenza H5N1 viruses. In Egypt, which is one of the H5N1 endemic areas for birds, pigeons are raised in towers built on farms in backyards and on house roofs, providing a potential risk for virus transmission from pigeons to humans. In this study, we performed genetic analysis of two H5N1 virus strains that were isolated from naturally infected pigeons in Egypt. Genetic and phylogenetic analyses showed that these viruses originated from Egyptian H5N1 viruses that were circulating in chickens or ducks. Several unique mutations, not reported before in any Egyptian isolates, were detected in the internal genes (i.e., polymerase residues PB1-V3D, PB1-K363R, PA-A369V, and PA-V602I; nucleoprotein residue NP-R38K; and nonstructural protein residues NS1-D120N and NS2-F55C). Our findings suggested that pigeons are naturally infected with H5N1 virus and can be a potential reservoir for transmission to humans, and showed the importance of genetic analysis of H5N1 internal genes.

  15. Experimental co-infections of domestic ducks with a virulent Newcastle disease virus and low or highly pathogenic avian influenza viruses.

    PubMed

    Pantin-Jackwood, Mary J; Costa-Hurtado, Mar; Miller, Patti J; Afonso, Claudio L; Spackman, Erica; Kapczynski, Darrell R; Shepherd, Eric; Smith, Diane; Swayne, David E

    2015-05-15

    Infections with avian influenza viruses (AIV) of low and high pathogenicity (LP and HP) and Newcastle disease virus (NDV) are commonly reported in domestic ducks in many parts of the world. However, it is not clear if co-infections with these viruses affect the severity of the diseases they produce, the amount of virus shed, and transmission of the viruses. In this study we infected domestic ducks with a virulent NDV virus (vNDV) and either a LPAIV or a HPAIV by giving the viruses individually, simultaneously, or sequentially two days apart. No clinical signs were observed in ducks infected or co-infected with vNDV and LPAIV, but co-infection decreased the number of ducks shedding vNDV and the amount of virus shed (P<0.01) at 4 days post inoculation (dpi). Co-infection did not affect the number of birds shedding LPAIV, but more LPAIV was shed at 2 dpi (P<0.0001) from ducks inoculated with only LPAIV compared to ducks co-infected with vNDV. Ducks that received the HPAIV with the vNDV simultaneously survived fewer days (P<0.05) compared to the ducks that received the vNDV two days before the HPAIV. Co-infection also reduced transmission of vNDV to naïve contact ducks housed with the inoculated ducks. In conclusion, domestic ducks can become co-infected with vNDV and LPAIV with no effect on clinical signs but with reduction of virus shedding and transmission. These findings indicate that infection with one virus can interfere with replication of another, modifying the pathogenesis and transmission of the viruses.

  16. Mammalian Innate Resistance to Highly Pathogenic Avian Influenza H5N1 Virus Infection Is Mediated through Reduced Proinflammation and Infectious Virus Release

    PubMed Central

    Nelli, Rahul K.; Dunham, Stephen P.; Kuchipudi, Suresh V.; White, Gavin A.; Baquero-Perez, Belinda; Chang, Pengxiang; Ghaemmaghami, Amir; Brookes, Sharon M.; Brown, Ian H.

    2012-01-01

    Respiratory epithelial cells and macrophages are the key innate immune cells that play an important role in the pathogenesis of influenza A virus infection. We found that these two cell types from both human and pig showed comparable susceptibilities to initial infection with a highly pathogenic avian influenza (HPAI) H5N1 virus (A/turkey/Turkey/1/05) and a moderately pathogenic human influenza H1N1 virus (A/USSR/77), but there were contrasting differences in host innate immune responses. Human cells mounted vigorous cytokine (tumor necrosis factor alpha [TNF-α] and interleukin-6 [IL-6]) and chemokine (CXCL9, CXCL10, and CXCL11) responses to H5N1 virus infection. However, pig epithelial cells and macrophages showed weak or no TNF-α and chemokine induction with the same infections. The apparent lack of a strong proinflammatory response, corroborated by the absence of TNF-α induction in H5N1 virus-challenged pigs, coincided with greater cell death and the reduced release of infectious virus from infected pig epithelial cells. Suppressor of cytokine signaling 3 (SOCS3), a protein suppressor of the JAK-STAT pathway, was constitutively highly expressed and transcriptionally upregulated in H5N1 virus-infected pig epithelial cells and macrophages, in contrast to the corresponding human cells. The overexpression of SOCS3 in infected human macrophages dampened TNF-α induction. In summary, we found that the reported low susceptibility of pigs to contemporary Eurasian HPAI H5N1 virus infections coincides at the level of innate immunity of respiratory epithelial cells and macrophages with a reduced output of viable virus and an attenuated proinflammatory response, possibly mediated in part by SOCS3, which could serve as a target in the treatment or prevention of virus-induced hypercytokinemia, as observed for humans. PMID:22718824

  17. Variability in pathobiology of South Korean H5N1 high-pathogenicity avian influenza virus infection for 5 species of migratory waterfowl

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The biological outcome of H5N1 high pathogenicity avian influenza (HPAI) virus infection in wild waterfowl is poorly understood. This study examined infectivity and pathobiology of A/chicken/Korea/IS/06 (H5N1) HPAI virus infection in Mute swans (Cygnus olor), Greylag geese (Anser anser), Ruddy Sheld...

  18. Human Pulmonary Microvascular Endothelial Cells Support Productive Replication of Highly Pathogenic Avian Influenza Viruses: Possible Involvement in the Pathogenesis of Human H5N1 Virus Infection

    PubMed Central

    Zeng, Hui; Pappas, Claudia; Belser, Jessica A.; Houser, Katherine V.; Zhong, Weiming; Wadford, Debra A.; Stevens, Troy; Balczon, Ron; Katz, Jacqueline M.

    2012-01-01

    Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to cause sporadic human infections with a high fatality rate. Respiratory failure due to acute respiratory distress syndrome (ARDS) is a complication among hospitalized patients. Since progressive pulmonary endothelial damage is the hallmark of ARDS, we investigated host responses following HPAI virus infection of human pulmonary microvascular endothelial cells. Evaluation of these cells for the presence of receptors preferred by influenza virus demonstrated that avian-like (α2-3-linked) receptors were more abundant than human-like (α2-6-linked) receptors. To test the permissiveness of pulmonary endothelial cells to virus infection, we compared the replication of selected seasonal, pandemic (2009 H1N1 and 1918), and potentially pandemic (H5N1) influenza virus strains. We observed that these cells support productive replication only of HPAI H5N1 viruses, which preferentially enter through and are released from the apical surface of polarized human endothelial monolayers. Furthermore, A/Thailand/16/2004 and A/Vietnam/1203/2004 (VN/1203) H5N1 viruses, which exhibit heightened virulence in mammalian models, replicated to higher titers than less virulent H5N1 strains. VN/1203 infection caused a significant decrease in endothelial cell proliferation compared to other subtype viruses. VN/1203 virus was also found to be a potent inducer of cytokines and adhesion molecules known to regulate inflammation during acute lung injury. Deletion of the H5 hemagglutinin (HA) multibasic cleavage site did not affect virus infectivity but resulted in decreased virus replication in endothelial cells. Our results highlight remarkable tropism and infectivity of the H5N1 viruses for human pulmonary endothelial cells, resulting in the potent induction of host inflammatory responses. PMID:22072765

  19. Prevention of immunodeficiency virus induced CD4+ T-cell depletion by prior infection with a non-pathogenic virus

    SciTech Connect

    TerWee, Julie A.; Carlson, Jennifer K.; Sprague, Wendy S.; Sondgeroth, Kerry S.; Shropshire, Sarah B.; Troyer, Jennifer L.; VandeWoude, Sue

    2008-07-20

    Immune dysregulation initiated by a profound loss of CD4+ T-cells is fundamental to HIV-induced pathogenesis. Infection of domestic cats with a non-pathogenic lentivirus prevalent in the puma (puma lentivirus, PLV or FIV{sub PCO}) prevented peripheral blood CD4+ T-cell depletion caused by subsequent virulent FIV infection. Maintenance of this critical population was not associated with a significant decrease in FIV viremia, lending support to the hypothesis that direct viral cytopathic effect is not the primary cause of immunodeficiency. Although this approach was analogous to immunization with a modified live vaccine, correlates of immunity such as a serum-neutralizing antibody or virus-specific T-cell proliferative response were not found in protected animals. Differences in cytokine transcription profile, most notably in interferon gamma, were observed between the protected and unprotected groups. These data provide support for the importance of non-adaptive enhancement of the immune response in the prevention of CD4+ T-cell loss.

  20. Previous infection with virulent strains of Newcastle disease virus reduces highly pathogenic avian influenza virus replication, disease, and mortality in chickens.

    PubMed

    Costa-Hurtado, Mar; Afonso, Claudio L; Miller, Patti J; Shepherd, Eric; Cha, Ra Mi; Smith, Diane; Spackman, Erica; Kapczynski, Darrell R; Suarez, David L; Swayne, David E; Pantin-Jackwood, Mary J

    2015-09-23

    Highly pathogenic avian influenza virus (HPAIV) and Newcastle disease virus (NDV) are two of the most important viruses affecting poultry worldwide and produce co-infections especially in areas of the world where both viruses are endemic; but little is known about the interactions between these two viruses. The objective of this study was to determine if co-infection with NDV affects HPAIV replication in chickens. Only infections with virulent NDV strains (mesogenic Pigeon/1984 or velogenic CA/2002), and not a lentogenic NDV strain (LaSota), interfered with the replication of HPAIV A/chicken/Queretaro/14588-19/95 (H5N2) when the H5N2 was given at a high dose (10(6.9) EID50) two days after the NDV inoculation, but despite this interference, mortality was still observed. However, chickens infected with the less virulent mesogenic NDV Pigeon/1984 strain three days prior to being infected with a lower dose (10(5.3-5.5) EID50) of the same or a different HPAIV, A/chicken/Jalisco/CPA-12283-12/2012 (H7N3), had reduced HPAIV replication and increased survival rates. In conclusion, previous infection of chickens with virulent NDV strains can reduce HPAIV replication, and consequently disease and mortality. This interference depends on the titer of the viruses used, the virulence of the NDV, and the timing of the infections. The information obtained from these studies helps to understand the possible interactions and outcomes of infection (disease and virus shedding) when HPAIV and NDV co-infect chickens in the field.

  1. Different routes of inoculation impact infectivity and pathogenesis of H5N1 high pathogenicity avian influenza virus infection in chickens and domestic ducks.

    PubMed

    Kwon, Y K; Swayne, D E

    2010-12-01

    The H5N1 type A influenza viruses classified as Qinghai-like virus (clade 2.2) are a unique lineage of type A influenza viruses with the capacity to produce significant disease and mortality in gallinaceous and anseriform birds, including domestic and wild ducks. The objective of this study was to determine the susceptibility and pathogenesis of chickens and domestic ducks to A/Whooper Swan/Mongolia/224/05 (H5N1) high pathogenicity avian influenza (HPAI) virus when administered through respiratory or alimentary routes of exposure. The chickens and ducks were more susceptible to the H5N1 HPAI virus, as evidenced by low infectious and lethal viral doses, when exposed by intranasal as compared to alimentary routes of inoculation (intragastric or oral-fed infected chicken meat). In the alimentary exposure pathogenesis study, pathologic changes included hemorrhage, necrosis, and inflammation in association with virus detection. These changes were generally observed in most of the visceral organs of chickens, between 2 and 4 days postinoculation (DPI), and are similar to lesions and virus localization seen in birds in natural cases or in experimental studies using the intranasal route. Alimentary exposure to the virus caused systemic infection in the ducks, characterized by moderate lymphocytic encephalitis, necrotized hepatitis, and pancreatitis with a corresponding demonstration of virus within the lesions. In both chickens and ducks with alimentary exposure, lesions, virus, or both were first demonstrated in the upper alimentary tract on 1 DPI, suggesting that the alimentary tract was the initial site affected upon consumption of infected meat or on gavage of virus in liquid medium. However, as demonstrated in the infectivity study in chickens, alimentary infection required higher exposure doses to produce infection as compared to intranasal exposure in chickens. These data suggest that upper respiratory exposure to H5N1 HPAI virus in birds is more likely to result in

  2. Dengue-specific CD8+ T cells have both protective and pathogenic roles in dengue virus infection.

    PubMed

    An, Jing; Zhou, De-Shan; Zhang, Jun-Lei; Morida, Hatue; Wang, Jia-Li; Yasui, Kotaro

    2004-09-01

    To analyze roles of memory T cells in the pathogenesis of dengue (DEN) virus infection, a DEN virus-specific CD8+ cell clone (2D42 cell) was employed to investigate its in vivo function after DEN virus infection using an animal model. HepG2 grafted severe combined immunodeficient (HepG2-grafted SCID) mice were divided into three groups--group A: HepG2-grafted SCID mice were inoculated intraperitoneally (ip) with 2D42 cells and then ip-infected with DEN virus type 2 (DEN-2); group B: HepG2-grafted SCID mice were inoculated with naive mouse thymocytes (NMT) and then ip-infected with DEN-2; group C: HepG2-grafted SCID mice were ip-infected with DEN-2 alone. Eighty percentage of group A mice died at average day 12.8 post-infection (p.i.) and 20% of them recovered from the disease after showing clinical signs and survived more than 3 months. They showed severe manifestations including dramatically decreased platelet count, decreased hematocrit, anemia, viremia and high frequency of histopathological changes in several organs. All of group B mice also showed the above severe clinical signs. One hundred percentage mortality rate was noted in these mice and death occurred at average day 10.8 p.i., which was the earliest among three groups. Although the mice from group C showed 100% mortality rate and similar clinical signs, death observed in these mice occurred at average day 17.4 p.i. and the manifestations were slight and developed slowly. Our results suggested both protective and pathogenic roles for DEN-specific CD8+ T cell in DEN virus infection, whereas NMT did not provided any protection.

  3. The Chinese highly pathogenic porcine reproductive and respiratory syndrome virus infection suppresses Th17 cells response in vivo.

    PubMed

    Zhang, Long; Zhou, Lei; Ge, Xinna; Guo, Xin; Han, Jun; Yang, Hanchun

    2016-06-30

    Porcine reproductive and respiratory syndrome virus (PRRSV) has been shown to immunomodulate innate and adaptive immunity of pigs. The Chinese highly pathogenic PRRSV (HP-PRRSV) infection causes severe bacterial secondary infection in pigs. However, the mechanism in relation to the bacterial secondary infection induced by HP-PRRSV remains unknown. In the present study, Th17 cells response in peripheral blood, lungs, spleens and lymph nodes of piglets were analyzed, and bacterial loads in lungs of piglets were examined upon HP-PRRSV infection. Meanwhile the changes of CD4(+) and CD8(+) T cells in peripheral blood of the inoculated piglets were analyzed. The results showed that HP-PRRSV-inoculated piglets exhibited a suppressed Th17 cells response in peripheral blood and a reduced number of Th17 cells in lungs, and higher bacterial loads in lungs, compared with low pathogenic PRRSV. Moreover, HP-PRRSV obviously resulted in severe depletion of porcine T cells in peripheral blood at the early stage of infection. These findings indicate that HP-PRRSV infection suppresses the response of Th17 cells that play an important role in combating bacterial infections, suggesting a possible correlation between the suppression of Th17 cells response in vivo and bacterial secondary infection induced by HP-PRRSV. Our present study adds a novel insight into better understanding of the pathogenesis of the Chinese HP-PRRSV.

  4. Highly (H5N1) and Low (H7N2) Pathogenic Avian Influenza Virus Infection in Falcons Via Nasochoanal Route and Ingestion of Experimentally Infected Prey

    PubMed Central

    Bertran, Kateri; Busquets, Núria; Abad, Francesc Xavier; García de la Fuente, Jorge; Solanes, David; Cordón, Iván; Costa, Taiana; Dolz, Roser; Majó, Natàlia

    2012-01-01

    An experimental infection with highly pathogenic avian influenza (HPAI) and low pathogenic avian influenza (LPAI) viruses was carried out on falcons in order to examine the effects of these viruses in terms of pathogenesis, viral distribution in tissues and viral shedding. The distribution pattern of influenza virus receptors was also assessed. Captive-reared gyr-saker (Falco rusticolus x Falco cherrug) hybrid falcons were challenged with a HPAI H5N1 virus (A/Great crested grebe/Basque Country/06.03249/2006) or a LPAI H7N2 virus (A/Anas plathyrhynchos/Spain/1877/2009), both via the nasochoanal route and by ingestion of previously infected specific pathogen free chicks. Infected falcons exhibited similar infection dynamics despite the different routes of exposure, demonstrating the effectiveness of in vivo feeding route. H5N1 infected falcons died, or were euthanized, between 5–7 days post-infection (dpi) after showing acute severe neurological signs. Presence of viral antigen in several tissues was confirmed by immunohistochemistry and real time RT-PCR (RRT-PCR), which were generally associated with significant microscopical lesions, mostly in the brain. Neither clinical signs, nor histopathological findings were observed in any of the H7N2 LPAI infected falcons, although all of them had seroconverted by 11 dpi. Avian receptors were strongly present in the upper respiratory tract of the falcons, in accordance with the consistent oral viral shedding detected by RRT-PCR in both H5N1 HPAI and H7N2 LPAI infected falcons. The present study demonstrates that gyr-saker hybrid falcons are highly susceptible to H5N1 HPAI virus infection, as previously observed, and that they may play a major role in the spreading of both HPAI and LPAI viruses. For the first time in raptors, natural infection by feeding on infected prey was successfully reproduced. The use of avian prey species in falconry husbandry and wildlife rehabilitation facilities could put valuable birds of prey

  5. Host-pathogen dynamics of squirrelpox virus infection in red squirrels (Sciurus vulgaris).

    PubMed

    Fiegna, C; Dagleish, M P; Coulter, L; Milne, E; Meredith, A; Finlayson, J; Di Nardo, A; McInnes, C J

    2016-01-01

    To improve our understanding of squirrelpox virus (SQPV) infection in the susceptible host, three red squirrels were challenged with wild-type SQPV via scarification of the hind-limb skin. All squirrels seroconverted to the infection by the end of the experiment (17 days post-challenge). Challenged animals suffered disease characterised by the development of multiple skin and oral lesions with rapid progression of skin lesions at the infection site by day 10 post-challenge. No internal pathological changes were found at post-mortem examination. A novel SQPV Taqman(®) Real-time PCR detected viral DNA from multiple organs, with the largest amounts consistently associated with the primary and secondary skin and oral lesions where viral replication was most likely occurring. Immunohistochemistry clearly detected viral antigen in the stratified squamous epithelium of the epidermis, tongue and the oropharyngeal mucosa-associated lymphoid tissue and was consistently associated with histological changes resulting from viral replication. The lack of internal pathological changes and the detection of relatively low levels of viral DNA when compared with primary and secondary skin lesions argue against systemic disease, although systemic spread of the virus cannot be ruled out. This study allowed a comprehensive investigation of the clinical manifestation and progression of SQPV infection with a quantitative and qualitative analysis of virus dissemination and shedding. These findings suggest two separate routes of SQPV transmission under natural conditions, with both skin and saliva playing key roles in infected red squirrels.

  6. Infection Risk for Persons Exposed to Highly Pathogenic Avian Influenza A H5 Virus-Infected Birds, United States, December 2014-March 2015.

    PubMed

    Arriola, Carmen S; Nelson, Deborah I; Deliberto, Thomas J; Blanton, Lenee; Kniss, Krista; Levine, Min Z; Trock, Susan C; Finelli, Lyn; Jhung, Michael A

    2015-12-01

    Newly emerged highly pathogenic avian influenza (HPAI) A H5 viruses have caused outbreaks among birds in the United States. These viruses differ genetically from HPAI H5 viruses that previously caused human illness, most notably in Asia and Africa. To assess the risk for animal-to-human HPAI H5 virus transmission in the United States, we determined the number of persons with self-reported exposure to infected birds, the number with an acute respiratory infection (ARI) during a 10-day postexposure period, and the number with ARI who tested positive for influenza by real-time reverse transcription PCR or serologic testing for each outbreak during December 15, 2014-March 31, 2015. During 60 outbreaks in 13 states, a total of 164 persons were exposed to infected birds. ARI developed in 5 of these persons within 10 days of exposure. H5 influenza virus infection was not identified in any persons with ARI, suggesting a low risk for animal-to-human HPAI H5 virus transmission.

  7. Experimental infection of IS/885/00-like infectious bronchitis virus in specific pathogen free and commercial broiler chicks.

    PubMed

    Awad, Faez; Chhabra, Rajesh; Forrester, Anne; Chantrey, Julian; Baylis, Matthew; Lemiere, Stephane; Hussein, Hussein Aly; Ganapathy, Kannan

    2016-04-01

    Pathogenesis of an IS/885/00-like (IS/885) strain of variant infectious bronchitis virus (IBV) was examined in one day old specific pathogen free (SPF) and commercial broiler chicks. Chicks were humanely euthanized at 3, 6, 9, 12, 15, 21 and 28 days post infection (dpi) for necropsy examination, and tissues were collected for histopathology and virus detection by reverse transcription polymerase chain reaction (RT-PCR). Respiratory clinical signs and gross lesions consisting of tracheal caseous exudate and plugs, and swollen kidneys (with or without) urate deposits were observed in SPF and broiler chicks. The onset of disease developed more slowly and were of lesser severity in broiler compared to SPF chicks, reflecting the inhibitory effects of the IBV maternal-antibodies in the broiler chicks or genetic/strain susceptibility, or both. Head swelling was observed in one infected broiler chick at 15 dpi and the virus was recovered by RT-PCR and isolation. In the IS/885-infected SPF chicks, cystic oviducts were found in two female chicks. IS/885 was isolated from the cystic fluid. Using ELISA, low to moderate levels of the antibodies to IBV was detected in the SPF compared to broiler infected chicks.

  8. Experimental infection with low and high pathogenicity H7N3 Chilean avian influenza viruses in Chiloe Wigeon (Anas sibilatrix) and Cinnamon Teal (Anas cyanoptera)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since 2002, H5N1 high pathogenicity avian influenza (HPAI) viruses have been associated with natural, lethal infections in wild aquatic birds which have been reproduced experimentally. Some aquatic bird species have been suggested as potential transporters of H5N1 HPAI virus via migration. However, ...

  9. Impact of vaccination on infection with Vietnam H5N1 high pathogenicity avian influenza virus in hens and the eggs they lay

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Highly pathogenic avian influenza virus (HPAIV) infections in chickens produce a negative impact on egg production, and virus is deposited on surface and internal contents of eggs. Previously, vaccination maintained egg production and reduced egg contamination when challenged with a North American H...

  10. Experimental infection of mandarin duck with highly pathogenic avian influenza A (H5N8 and H5N1) viruses.

    PubMed

    Kang, Hyun-Mi; Lee, Eun-Kyoung; Song, Byung-Min; Heo, Gyeong-Beom; Jung, Joojin; Jang, Il; Bae, You-Chan; Jung, Suk Chan; Lee, Youn-Jeong

    2017-01-01

    A highly pathogenic avian influenza (HPAI) H5N8 virus was first detected in poultry and wild birds in South Korea in January 2014. Here, we determined the pathogenicity and transmissibility of three different clades of H5 viruses in mandarin ducks to examine the potential for wild bird infection. H5N8 (clade 2.3.4.4) replicated more efficiently in the upper and lower respiratory tract of mandarin ducks than two previously identified H5N1 virus clades (clades 2.2 and 2.3.2.1). However, none of the mandarin ducks infected with H5N8 and H5N1 viruses showed severe clinical signs or mortality, and gross lesions were only observed in a few tissues. Viral replication and shedding were greater in H5N8-infected ducks than in H5N1-infected ducks. Recovery of all viruses from control duck in contact with infected ducks indicated that the highly pathogenic H5 viruses spread horizontally through contact. Taken together, these results suggest that H5N8 viruses spread efficiently in mandarin ducks. Further studies of pathogenicity in wild birds are required to examine possible long-distance dissemination via migration routes.

  11. Pathogenesis of highly pathogenic avian influenza A virus (H7N1) infection in chickens inoculated with three different doses.

    PubMed

    Chaves, Aida J; Busquets, Nuria; Campos, Naiana; Ramis, Antonio; Dolz, Roser; Rivas, Raquel; Valle, Rosa; Abad, F Xavier; Darji, Ayub; Majo, Natalia

    2011-04-01

    To study the pathogenesis of a H7N1 highly pathogenic avian influenza virus strain, specific pathogen free chickens were inoculated with decreasing concentrations of virus: 10(5.5) median embryo lethal dose (ELD(50)) (G1), 10(3.5) ELD(50) (G2) and 10(1.5) ELD(50) (G3). Disease progression was monitored over a period of 16 days and sequential necropsies and tissue samples were collected for histological and immunohistochemical examination. Viral RNA loads were also quantified in different tissues, blood, oropharyngeal swabs, and cloacal swabs using quantitative real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). Clinical signs of depression, apathy, listlessness, huddling and ruffled feathers were recorded in G1 and a few G2 birds, whilst neurological signs were only observed in chickens inoculated with the highest dose. Gross lesions of haemorrhages were observed in the unfeathered skin of the comb and legs, and skeletal muscle, lung, pancreas and kidneys of birds inoculated with 10(5.5) ELD(50) and 10(3.5) ELD(50) doses. Microscopic lesions and viral antigen were demonstrated in cells of the nasal cavity, lung, heart, skeletal muscle, brain, spinal cord, gastrointestinal tract, pancreas, liver, bone marrow, thymus, bursa of Fabricius, spleen, kidney, adrenal gland and skin. Viral RNA was detected by RT-qPCR in kidney, lung, intestine, and brain samples of G1 and G2 birds. However, in birds infected with the lowest dose, viral RNA was detected only in brain and lung samples in low amounts at 5 and 7 days post infection. Interestingly, viral shedding was observed in oropharyngeal and cloacal swabs with proportionate decrease with the inoculation dose. We conclude that although an adequate infectious dose is critical in reproducing the clinical infection, chickens exposed to lower doses can be infected and shed virus representing a risk for the dissemination of the viral agent.

  12. Pathobiology of highly pathogenic avian influenza virus H5N2 infection in juvenile ostriches from South Africa.

    PubMed

    Howerth, Elizabeth W; Olivier, Adriaan; França, Monique; Stallknecht, David E; Gers, Sophette

    2012-12-01

    In 2011, over 35,000 ostriches were slaughtered in the Oudtshoorn district of the Western Cape province of South Africa following the diagnosis of highly pathogenic avian influenza virus H5N2. We describe the pathology and virus distribution via immunohistochemistry in juvenile birds that died rapidly in this outbreak after showing signs of depression and weakness. Associated sialic acid (SA) receptor distribution in uninfected birds is also described. At necropsy, enlarged spleens, swollen livers, and generalized congestion were noted. Birds not succumbing to acute influenza infection often became cachectic with serous atrophy of fat, airsacculitis, and secondary infections. Necrotizing hepatitis, splenitis, and airsacculitis were prominent histopathologic findings. Virus was detected via immunohistochemistry in abundance in the liver and spleen but also in the air sac and gastrointestinal tract. Infected cells included epithelium, endothelium, macrophages, circulating leukocytes, and smooth muscle of a variety of organs and vessel walls. Analysis of SA receptor distribution in uninfected juvenile ostriches via lectin binding showed abundant expression of SAalpha2,3Gal (avian type) and little or no expression of SAalpha2,6Gal (human type) in the gastrointestinal and respiratory tracts, as well as leukocytes in the spleen and endothelial cells in all organs, which correlated with H5N2 antigen distribution in these tissues.

  13. 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

  14. Resistant Pathogens, Fungi, and Viruses

    PubMed Central

    Guidry, Christopher A.; Mansfield, Sara A.; Sawyer, Robert G.; Cook, Charles H.

    2014-01-01

    The first reports of antibiotic pathogens occurred a few short years after the introduction of these powerful new agents, heralding a new kind of war between medicine and pathogens. Although originally described in Staphylococcus aureus, resistance among bacteria has now become a grim race to determine which classes of bacteria will become more resistant, pitting the Gram positive staphylococci, enterococci, and streptococci against the increasingly resistant Gram negative pathogens, e. g., carbapenemase-resistant enterobacteriaceae. In addition, the availability of antibacterial agents has allowed the development of whole new kinds of diseases caused by non-bacterial pathogens, related largely to fungi that are inherently resistant to antibacterials. All of these organisms are becoming more prevalent and, ultimately, more clinically relevant for surgeons. It is ironic that despite their ubiquity in our communities, there is seldom a second thought given to viral infections in patients with surgical illness. The extent of most surgeon’s interest in viral infections ends with hepatitis and HIV, no doubt related to transmissibility as well as the implications that these viruses might have in a patient’s hepatic or immune functions. There are chapters and even textbooks written about these viruses so these will not be considered here. Instead, we will present the growing body of knowledge of the herpes family viruses and their occurrence and consequences in patients with concomitant surgical disease or critical illness. We have also chosen to focus this chapter on previously immune competent patients, as the impact of herpes family viruses in immunosuppressed patients such as transplant or AIDS patients has received thorough treatment elsewhere. PMID:25440119

  15. Experimental infection of mallard ducks with different subtype H5 and H7 highly pathogenic avian influenza viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Highly pathogenic avian influenza viruses (HPAIV’s) remain a threat to poultry worldwide. Avian influenza viruses, including HPAIV, are usually non-pathogenic for ducks and other wild aquatic birds, with the exception of some Asian lineage H5N1 HPAIVs which can cause severe disease in ducks. With ...

  16. Multi-Year Pathogen Survey of Biofuel Switchgrass Breeding Plots Reveals High Prevalence of Infections by Panicum mosaic virus and Its Satellite Virus.

    PubMed

    Stewart, Catherine L; Pyle, Jesse D; Jochum, Charlene C; Vogel, Kenneth P; Yuen, Gary Y; Scholthof, Karen-Beth G

    2015-08-01

    Switchgrass (Panicum virgatum) cultivars are currently under development as lignocellulosic feedstock. Here we present a survey of three established switchgrass experimental nurseries in Nebraska in which we identified Panicum mosaic virus (PMV) as the most prevalent virus. In 2012, 72% of 139 symptomatic plants tested positive for PMV. Of the PMV-positive samples, 19% were coinfected with its satellite virus (SPMV). Less than 14% of all sampled plants in 2012 were positive for four additional viruses known to infect switchgrass. In 2013, randomized sampling of switchgrass individuals from the same 2012 breeding plots revealed that infection by PMV or PMV+SPMV was both more prevalent and associated with more severe symptoms in the cultivar Summer, and experimental lines with Summer parentage, than populations derived from the cultivar Kanlow. A 3-year analysis, from 2012 to 2014, showed that previously uninfected switchgrass plants acquire PMV or PMV+SPMV between harvest cycles. In contrast, some plants apparently did not maintain PMV infections at detectable levels from year-to-year. These findings suggest that PMV and SPMV should be considered important pathogens of switchgrass and serious potential threats to biofuel crop production efficiency.

  17. Short-Term Heat Shock Affects Host–Virus Interaction in Mice Infected with Highly Pathogenic Avian Influenza Virus H5N1

    PubMed Central

    Xue, Jia; Fan, Xiaoxu; Yu, Jing; Zhang, Shouping; Xiao, Jin; Hu, Yanxin; Wang, Ming

    2016-01-01

    Highly pathogenic avian influenza virus (HPAIV) H5N1 is a highly contagious virus that can cause acute respiratory infections and high human fatality ratio due to excessive inflammatory response. Short-term heat shock, as a stressful condition, could induce the expression of heat shock proteins that function as molecular chaperones to protect cells against multiple stresses. However, the protective effect of short-term heat shock in influenza infection is far from being understood. In this study, mice were treated at 39°C for 4 h before being infected with HPAIV H5N1. Interestingly, short-term heat shock significantly increased the levels of HSP70 and pro-inflammatory cytokines IL-6, TNF-α, IFN-β, and IFN-γ in the lung tissues of mice. Following HPAIV H5N1 infection, short-term heat shock alleviated immunopathology and viral replication in lung tissue and repressed the weight loss and increased the survival rate of H5N1-infected mice. Our data reported that short-term heat shock provided beneficial anti-HPAIV H5N1 properties in mice model, which offers an alternative strategy for non-drug prevention for influenza infection. PMID:27379054

  18. Short-Term Heat Shock Affects Host-Virus Interaction in Mice Infected with Highly Pathogenic Avian Influenza Virus H5N1.

    PubMed

    Xue, Jia; Fan, Xiaoxu; Yu, Jing; Zhang, Shouping; Xiao, Jin; Hu, Yanxin; Wang, Ming

    2016-01-01

    Highly pathogenic avian influenza virus (HPAIV) H5N1 is a highly contagious virus that can cause acute respiratory infections and high human fatality ratio due to excessive inflammatory response. Short-term heat shock, as a stressful condition, could induce the expression of heat shock proteins that function as molecular chaperones to protect cells against multiple stresses. However, the protective effect of short-term heat shock in influenza infection is far from being understood. In this study, mice were treated at 39°C for 4 h before being infected with HPAIV H5N1. Interestingly, short-term heat shock significantly increased the levels of HSP70 and pro-inflammatory cytokines IL-6, TNF-α, IFN-β, and IFN-γ in the lung tissues of mice. Following HPAIV H5N1 infection, short-term heat shock alleviated immunopathology and viral replication in lung tissue and repressed the weight loss and increased the survival rate of H5N1-infected mice. Our data reported that short-term heat shock provided beneficial anti-HPAIV H5N1 properties in mice model, which offers an alternative strategy for non-drug prevention for influenza infection.

  19. Progression of pathogenic events in cynomolgus macaques infected with variola virus.

    PubMed

    Wahl-Jensen, Victoria; Cann, Jennifer A; Rubins, Kathleen H; Huggins, John W; Fisher, Robert W; Johnson, Anthony J; de Kok-Mercado, Fabian; Larsen, Thomas; Raymond, Jo Lynne; Hensley, Lisa E; Jahrling, Peter B

    2011-01-01

    Smallpox, caused by variola virus (VARV), is a devastating human disease that affected millions worldwide until the virus was eradicated in the 1970 s. Subsequent cessation of vaccination has resulted in an immunologically naive human population that would be at risk should VARV be used as an agent of bioterrorism. The development of antivirals and improved vaccines to counter this threat would be facilitated by the development of animal models using authentic VARV. Towards this end, cynomolgus macaques were identified as adequate hosts for VARV, developing ordinary or hemorrhagic smallpox in a dose-dependent fashion. To further refine this model, we performed a serial sampling study on macaques exposed to doses of VARV strain Harper calibrated to induce ordinary or hemorrhagic disease. Several key differences were noted between these models. In the ordinary smallpox model, lymphoid and myeloid hyperplasias were consistently found whereas lymphocytolysis and hematopoietic necrosis developed in hemorrhagic smallpox. Viral antigen accumulation, as assessed immunohistochemically, was mild and transient in the ordinary smallpox model. In contrast, in the hemorrhagic model antigen distribution was widespread and included tissues and cells not involved in the ordinary model. Hemorrhagic smallpox developed only in the presence of secondary bacterial infections - an observation also commonly noted in historical reports of human smallpox. Together, our results support the macaque model as an excellent surrogate for human smallpox in terms of disease onset, acute disease course, and gross and histopathological lesions.

  20. 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.

  1. Human infection with a highly pathogenic avian influenza A (H5N6) virus in Yunnan province, China.

    PubMed

    Xu, Wen; Li, Hong; Jiang, Li

    2016-01-01

    Highly pathogenic avian influenza A H5N6 virus has caused four human infections in China. This study reports the preliminary findings of the first known human case of H5N6 in Yunnan province. The patient initially developed symptoms of sore throat and coughing on 27 January 2015. The disease rapidly progressed to severe pneumonia, multiple organ dysfunctions and acute respiratory distress syndrome and the patient died on 6 February. Virological analysis determined that the virus belonged to H5 clade 2.3.4.4 and it has obtained partial ability for mammalian adaptation and amantadine resistance. Environmental investigation found H5 in 63% of the samples including poultry faeces, tissues, cage surface swabs and sewage from local live poultry markets by real-time RT-PCR. These findings suggest that the expanding and enhancing of surveillance in both avian and humans are necessary to monitor the evolution of H5 influenza virus and to facilitate early detection of suspected cases.

  2. Previous infection with virulent strains of Newcastle disease virus reduces highly pathogenic avian influenza virus replication, disease, and mortality 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 about the interaction between these two viruses when simultaneously co-infecting the same host, especially in areas of the world where both viruses are...

  3. Replication of 2 subtypes of low-pathogenicity avian influenza virus of duck and gull origins in experimentally infected Mallard ducks.

    PubMed

    Daoust, P-Y; van de Bildt, M; van Riel, D; van Amerongen, G; Bestebroer, T; Vanderstichel, R; Fouchier, R A M; Kuiken, T

    2013-05-01

    Many subtypes of low-pathogenicity avian influenza (LPAI) virus circulate in wild bird reservoirs, but their prevalence may vary among species. We aimed to compare by real-time reverse-transcriptase polymerase chain reaction, virus isolation, histology, and immunohistochemistry the distribution and pathogenicity of 2 such subtypes of markedly different origins in Mallard ducks (Anas platyrhynchos): H2N3 isolated from a Mallard duck and H13N6 isolated from a Ring-billed Gull (Larus delawarensis). Following intratracheal and intraesophageal inoculation, neither virus caused detectable clinical signs, although H2N3 virus infection was associated with a significantly decreased body weight gain during the period of virus shedding. Both viruses replicated in the lungs and air sacs until approximately day 3 after inoculation and were associated with a locally extensive interstitial, exudative, and proliferative pneumonia. Subtype H2N3, but not subtype H13N6, went on to infect the epithelia of the intestinal mucosa and cloacal bursa, where it replicated without causing lesions until approximately day 5 after inoculation. Larger quantities of subtype H2N3 virus were detected in cloacal swabs than in pharyngeal swabs. The possible clinical significance of LPAI virus-associated pulmonary lesions and intestinal tract infection in ducks deserves further evaluation.

  4. 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.

  5. Histopathological characterization and shedding dynamics of guineafowl (Numida meleagris) intravenously infected with a H6N2 low pathogenicity Avian Influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Guineafowl of different ages were inoculated intravenously with an H6N2 wild waterfowl-origin low-pathogenicity type A avian influenza virus (LPAI). No evidence of clinical disease was observed. The examined infected birds had atrophy of the spleen, thymus, and cloacal bursa when compared to the n...

  6. Impact of vaccination on infection with Vietnam H5N1 high pathogenicity avian influenza virus in hens and the eggs they lay

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High pathogenicity avian influenza virus (HPAIV) infections in chickens decrease egg production and eggs that are laid contain HPAIV. Vaccination once or twice was examined as a way to protect chickens from Vietnamese H5N1 HPAIV. Eighty-three percent of hens without vaccination died within 3 days ...

  7. Molecular signatures associated with Mx-1 mediated resistance to highlyl pathogenic influenza virus infections: mechanisms of survival

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Understanding the role of host factors during lethal influenza virus infection is critical to deciphering the events that will determine the fate of the host. One such factor is encoded by the Mx1 gene, which confers resistance to influenza virus infection. Here, we compared pathology and global g...

  8. Encephalitis in a stone marten (Martes foina) after natural infection with highly pathogenic avian influenza virus subtype H5N1.

    PubMed

    Klopfleisch, R; Wolf, P U; Wolf, C; Harder, T; Starick, E; Niebuhr, M; Mettenleiter, T C; Teifke, J P

    2007-01-01

    Recent outbreaks of disease in different avian species, caused by the highly pathogenic avian influenza virus (HPAIV), have involved infection by subtype H5N1 of the virus. This virus has also crossed species barriers and infected felines and humans. Here, we report the natural infection of a stone marten (Martes foina) from an area with numerous confirmed cases of H5N1 HPAIV infection in wild birds. Histopathological examination of tissues from this animal revealed a diffuse nonsuppurative panencephalitis with perivascular cuffing, multifocal gliosis and neuronal necrosis. Additionally, focal necrosis of pancreatic acinar cells was observed. Immunohistochemically, lesions in these organs were associated with avian influenza virus antigen in neurons, glial cells and pancreatic acinar cells. Thus, the microscopical lesions and viral antigen distribution in this stone marten differs from that recently described for cats naturally and experimentally infected with the same virus subtype. This is the first report of natural infection of a mustelid with HPAIV H5N1.

  9. Survival analysis of infected mice reveals pathogenic variations in the genome of avian H1N1 viruses.

    PubMed

    Koçer, Zeynep A; Fan, Yiping; Huether, Robert; Obenauer, John; Webby, Richard J; Zhang, Jinghui; Webster, Robert G; Wu, Gang

    2014-12-12

    Most influenza pandemics have been caused by H1N1 viruses of purely or partially avian origin. Here, using Cox proportional hazard model, we attempt to identify the genetic variations in the whole genome of wild-type North American avian H1N1 influenza A viruses that are associated with their virulence in mice by residue variations, host origins of virus (Anseriformes-ducks or Charadriiformes-shorebirds), and host-residue interactions. In addition, through structural modeling, we predicted that several polymorphic sites associated with pathogenicity were located in structurally important sites, especially in the polymerase complex and NS genes. Our study introduces a new approach to identify pathogenic variations in wild-type viruses circulating in the natural reservoirs and ultimately to understand their infectious risks to humans as part of risk assessment efforts towards the emergence of future pandemic strains.

  10. Experimental infection of bar-headed geese (Anser indicus) and ruddy shelducks (Tadorna ferruginea) with a clade 2.3.2 H5N1 highly pathogenic avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since 2005, clade 2.2 H5N1 highly pathogenic avian influenza (HPAI) viruses have caused infections and disease involving numerous species of wild waterfowl in Eurasia and Africa. However, outbreaks associated with clade 2.3.2 viruses have increased since 2009, and viruses within this clade have beco...

  11. Pathologic Changes in Wild Birds Infected with Highly Pathogenic Avian Influenza A(H5N8) Viruses, South Korea, 2014.

    PubMed

    Kim, Hye-Ryoung; Kwon, Yong-Kuk; Jang, Il; Lee, Youn-Jeong; Kang, Hyun-Mi; Lee, Eun-Kyoung; Song, Byung-Min; Lee, Hee-Soo; Joo, Yi-Seok; Lee, Kyung-Hyun; Lee, Hyun-Kyoung; Baek, Kang-Hyun; Bae, You-Chan

    2015-05-01

    In January 2014, an outbreak of infection with highly pathogenic avian influenza (HPAI) A(H5N8) virus began on a duck farm in South Korea and spread to other poultry farms nearby. During this outbreak, many sick or dead wild birds were found around habitats frequented by migratory birds. To determine the causes of death, we examined 771 wild bird carcasses and identified HPAI A(H5N8) virus in 167. Gross and histologic lesions were observed in pancreas, lung, brain, and kidney of Baikal teals, bean geese, and whooper swans but not mallard ducks. Such lesions are consistent with lethal HPAI A(H5N8) virus infection. However, some HPAI-positive birds had died of gunshot wounds, peritonitis, or agrochemical poisoning rather than virus infection. These findings suggest that susceptibility to HPAI A(H5N8) virus varies among species of migratory birds and that asymptomatic migratory birds could be carriers of this virus.

  12. Pathologic Changes in Wild Birds Infected with Highly Pathogenic Avian Influenza A(H5N8) Viruses, South Korea, 2014

    PubMed Central

    Kim, Hye-Ryoung; Kwon, Yong-Kuk; Jang, Il; Lee, Youn-Jeong; Kang, Hyun-Mi; Lee, Eun-Kyoung; Song, Byung-Min; Lee, Hee-Soo; Joo, Yi-Seok; Lee, Kyung-Hyun; Lee, Hyun-Kyoung; Baek, Kang-Hyun

    2015-01-01

    In January 2014, an outbreak of infection with highly pathogenic avian influenza (HPAI) A(H5N8) virus began on a duck farm in South Korea and spread to other poultry farms nearby. During this outbreak, many sick or dead wild birds were found around habitats frequented by migratory birds. To determine the causes of death, we examined 771 wild bird carcasses and identified HPAI A(H5N8) virus in 167. Gross and histologic lesions were observed in pancreas, lung, brain, and kidney of Baikal teals, bean geese, and whooper swans but not mallard ducks. Such lesions are consistent with lethal HPAI A(H5N8) virus infection. However, some HPAI-positive birds had died of gunshot wounds, peritonitis, or agrochemical poisoning rather than virus infection. These findings suggest that susceptibility to HPAI A(H5N8) virus varies among species of migratory birds and that asymptomatic migratory birds could be carriers of this virus. PMID:25897841

  13. Picturing pathogen infection in plants.

    PubMed

    Barón, Matilde; Pineda, Mónica; Pérez-Bueno, María Luisa

    2016-09-01

    Several imaging techniques have provided valuable tools to evaluate the impact of biotic stress on host plants. The use of these techniques enables the study of plant-pathogen interactions by analysing the spatial and temporal heterogeneity of foliar metabolism during pathogenesis. In this work we review the use of imaging techniques based on chlorophyll fluorescence, multicolour fluorescence and thermography for the study of virus, bacteria and fungi-infected plants. These studies have revealed the impact of pathogen challenge on photosynthetic performance, secondary metabolism, as well as leaf transpiration as a promising tool for field and greenhouse management of diseases. Images of standard chlorophyll fluorescence (Chl-F) parameters obtained during Chl-F induction kinetics related to photochemical processes and those involved in energy dissipation, could be good stress indicators to monitor pathogenesis. Changes on UV-induced blue (F440) and green fluorescence (F520) measured by multicolour fluorescence imaging in pathogen-challenged plants seem to be related with the up-regulation of the plant secondary metabolism and with an increase in phenolic compounds involved in plant defence, such as scopoletin, chlorogenic or ferulic acids. Thermal imaging visualizes the leaf transpiration map during pathogenesis and emphasizes the key role of stomata on innate plant immunity. Using several imaging techniques in parallel could allow obtaining disease signatures for a specific pathogen. These techniques have also turned out to be very useful for presymptomatic pathogen detection, and powerful non-destructive tools for precision agriculture. Their applicability at lab-scale, in the field by remote sensing, and in high-throughput plant phenotyping, makes them particularly useful. Thermal sensors are widely used in crop fields to detect early changes in leaf transpiration induced by both air-borne and soil-borne pathogens. The limitations of measuring photosynthesis by

  14. Metagenomic detection of viral pathogens in Spanish honeybees: co-infection by Aphid Lethal Paralysis, Israel Acute Paralysis and Lake Sinai Viruses.

    PubMed

    Granberg, Fredrik; Vicente-Rubiano, Marina; Rubio-Guerri, Consuelo; Karlsson, Oskar E; Kukielka, Deborah; Belák, Sándor; Sánchez-Vizcaíno, José Manuel

    2013-01-01

    The situation in Europe concerning honeybees has in recent years become increasingly aggravated with steady decline in populations and/or catastrophic winter losses. This has largely been attributed to the occurrence of a variety of known and "unknown", emerging novel diseases. Previous studies have demonstrated that colonies often can harbour more than one pathogen, making identification of etiological agents with classical methods difficult. By employing an unbiased metagenomic approach, which allows the detection of both unexpected and previously unknown infectious agents, the detection of three viruses, Aphid Lethal Paralysis Virus (ALPV), Israel Acute Paralysis Virus (IAPV), and Lake Sinai Virus (LSV), in honeybees from Spain is reported in this article. The existence of a subgroup of ALPV with the ability to infect bees was only recently reported and this is the first identification of such a strain in Europe. Similarly, LSV appear to be a still unclassified group of viruses with unclear impact on colony health and these viruses have not previously been identified outside of the United States. Furthermore, our study also reveals that these bees carried a plant virus, Turnip Ringspot Virus (TuRSV), potentially serving as important vector organisms. Taken together, these results demonstrate the new possibilities opened up by high-throughput sequencing and metagenomic analysis to study emerging new diseases in domestic and wild animal populations, including honeybees.

  15. Experimental infection of highly and low pathogenic avian influenza viruses to chickens, ducks, tree sparrows, jungle crows, and black rats for the evaluation of their roles in virus transmission.

    PubMed

    Hiono, Takahiro; Okamatsu, Masatoshi; Yamamoto, Naoki; Ogasawara, Kohei; Endo, Mayumi; Kuribayashi, Saya; Shichinohe, Shintaro; Motohashi, Yurie; Chu, Duc-Huy; Suzuki, Mizuho; Ichikawa, Takaya; Nishi, Tatsuya; Abe, Yuri; Matsuno, Keita; Tanaka, Kazuyuki; Tanigawa, Tsutomu; Kida, Hiroshi; Sakoda, Yoshihiro

    2016-01-01

    Highly pathogenic avian influenza viruses (HPAIVs) have spread in both poultry and wild birds. Determining transmission routes of these viruses during an outbreak is essential for the control of avian influenza. It has been widely postulated that migratory ducks play crucial roles in the widespread dissemination of HPAIVs in poultry by carrying viruses along with their migrations; however close contacts between wild migratory ducks and poultry are less likely in modern industrial poultry farming settings. Therefore, we conducted experimental infections of HPAIVs and low pathogenic avian influenza viruses (LPAIVs) to chickens, domestic ducks, tree sparrows, jungle crows, and black rats to evaluate their roles in virus transmission. The results showed that chickens, ducks, sparrows, and crows were highly susceptible to HPAIV infection. Significant titers of virus were recovered from the sparrows and crows infected with HPAIVs, which suggests that they potentially play roles of transmission of HPAIVs to poultry. In contrast, the growth of LPAIVs was limited in each of the animals tested compared with that of HPAIVs. The present results indicate that these common synanthropes play some roles in influenza virus transmission from wild birds to poultry.

  16. Derivation and Characterization of Pathogenic Transmitted/Founder Molecular Clones from Simian Immunodeficiency Virus SIVsmE660 and SIVmac251 following Mucosal Infection

    PubMed Central

    Lopker, Michael J.; Del Prete, Gregory Q.; Estes, Jacob D.; Li, Hui; Reid, Carolyn; Newman, Laura; Lipkey, Leslie; Camus, Celine; Easlick, Juliet L.; Wang, Shuyi; Decker, Julie M.; Bar, Katharine J.; Learn, Gerald; Pal, Ranajit; Weiss, Deborah E.; Hahn, Beatrice H.; Lifson, Jeffrey D.; Shaw, George M.

    2016-01-01

    ABSTRACT Currently available simian immunodeficiency virus (SIV) infectious molecular clones (IMCs) and isolates used in nonhuman primate (NHP) models of AIDS were originally derived from infected macaques during chronic infection or end stage disease and may not authentically recapitulate features of transmitted/founder (T/F) genomes that are of particular interest in transmission, pathogenesis, prevention, and treatment studies. We therefore generated and characterized T/F IMCs from genetically and biologically heterogeneous challenge stocks of SIVmac251 and SIVsmE660. Single-genome amplification (SGA) was used to identify full-length T/F genomes present in plasma during acute infection resulting from atraumatic rectal inoculation of Indian rhesus macaques with low doses of SIVmac251 or SIVsmE660. All 8 T/F clones yielded viruses that were infectious and replication competent in vitro, with replication kinetics similar to those of the widely used chronic-infection-derived IMCs SIVmac239 and SIVsmE543. Phenotypically, the new T/F virus strains exhibited a range of neutralization sensitivity profiles. Four T/F virus strains were inoculated into rhesus macaques, and each exhibited typical SIV replication kinetics. The SIVsm T/F viruses were sensitive to TRIM5α restriction. All T/F viruses were pathogenic in rhesus macaques, resulting in progressive CD4+ T cell loss in gastrointestinal tissues, peripheral blood, and lymphatic tissues. The animals developed pathological immune activation; lymphoid tissue damage, including fibrosis; and clinically significant immunodeficiency leading to AIDS-defining clinical endpoints. These T/F clones represent a new molecular platform for the analysis of virus transmission and immunopathogenesis and for the generation of novel “bar-coded” challenge viruses and next-generation simian-human immunodeficiency viruses that may advance the HIV/AIDS vaccine agenda. IMPORTANCE Nonhuman primate research has relied on only a few

  17. Biological characterization of highly pathogenic avian influenza H5N1 viruses that infected humans in Egypt in 2014-2015.

    PubMed

    El-Shesheny, Rabeh; Mostafa, Ahmed; Kandeil, Ahmed; Mahmoud, Sara H; Bagato, Ola; Naguib, Amel; Refaey, Samir El; Webby, Richard J; Ali, Mohamed A; Kayali, Ghazi

    2017-03-01

    Highly pathogenic avian influenza (HPAI) H5N1 influenza viruses emerged as a human pathogen in 1997 with expected potential to undergo sustained human-to-human transmission and pandemic viral spread. HPAI H5N1 is endemic in Egyptian poultry and has caused sporadic human infection. The first outbreak in early 2006 was caused by clade 2.2 viruses that rapidly evolved genetically and antigenically. A sharp increase in the number of human cases was reported in Egypt in the 2014/2015 season. In this study, we analyzed and characterized three isolates of HPAI H5N1 viruses isolated from infected humans in Egypt in 2014/2015. Phylogenetic analysis demonstrated that the nucleotide sequences of eight segments of the three isolates were clustered with those of members of clade 2.2.1.2. We also found that the human isolates from 2014/2015 had a slight, non-significant difference in their affinity for human-like sialic acid receptors. In contrast, they showed significant differences in their replication kinetics in MDCK, MDCK-SIAT, and A549 cells as well as in embryonated chicken eggs. An antiviral bioassay study revealed that all of the isolates were susceptible to amantadine. Therefore, further investigation and monitoring is required to correlate the genetic and/or antigenic changes of the emerging HPAI H5N1 viruses with possible alteration in their characteristics and their potential to become a further threat to public health.

  18. 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

  19. 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.

  20. Genetics and infectivity of H5N1 highly pathogenic avian influenza viruses isolated from chickens and wild birds in Japan during 2010-11.

    PubMed

    Uchida, Yuko; Suzuki, Yasushi; Shirakura, Masayuki; Kawaguchi, Akira; Nobusawa, Eri; Tanikawa, Taichiro; Hikono, Hirokazu; Takemae, Nobuhiro; Mase, Masaji; Kanehira, Katsushi; Hayashi, Tsuyoshi; Tagawa, Yuichi; Tashiro, Masato; Saito, Takehiko

    2012-12-01

    Outbreaks of H5N1 subtype highly pathogenic avian influenza virus (HPAIV) were recorded in chickens, domesticated birds and wild birds throughout Japan from November 2010 to March 2011. Genetic analysis of the Japanese isolates indicated that all gene segments, except the PA gene, were closely related to Japanese wild bird isolates in 2008 and belonged to clade 2.3.2.1 classified by the WHO/OIE/FAO H5N1 Evolution Working Group. Direct ancestors of the PA gene segment of all Japanese viruses analyzed in this study can be found in wild bird strains of several subtypes other than H5N1 isolated between 2007 and 2009. The PA gene of these wild bird isolates share a common ancestor with H5N1 HPAIVs belonging to clades 2.5, 7 and 9, indicating that wild birds were involved in the emergence of the current reassortant 2.3.2.1 viruses. To determine how viruses were maintained in the wild bird population, two isolates derived from chickens (A/chicken/Shimane/1/2010, Ck10 and A/chicken/Miyazaki/S4/2011, CkS411) and one from a wild bird (A/mandarin duck/Miyazaki/22M-765/2011, MandarinD11) were compared in their ability to infect and be transmitted to chickens. There was a significant difference in the survival of chickens that were infected with 10(6)EID(50) of CkS411 compared to those with MandarinD11 and the transmission efficiency of CkS411 was greater than the other viruses. The increased titer of CkS411 excreted from infected chickens contributed to the improved transmission rates. It was considered that reduced virus excretion and transmission of MandarinD11 could have been due to adaptation of the virus in wild birds.

  1. Human microRNA-24 modulates highly pathogenic avian-origin H5N1 influenza A virus infection in A549 cells by targeting secretory pathway furin.

    PubMed

    Loveday, Emma-Kate; Diederich, Sandra; Pasick, John; Jean, François

    2015-01-01

    A common critical cellular event that many human enveloped viruses share is the requirement for proteolytic cleavage of the viral glycoprotein by furin in the host secretory pathway. For example, the furin-dependent proteolytic activation of highly pathogenic (HP) influenza A (infA) H5 and H7 haemagglutinin precursor (HA0) subtypes is critical for yielding fusion-competent infectious virions. In this study, we hypothesized that viral hijacking of the furin pathway by HP infA viruses to permit cleavage of HA0 could represent a novel molecular mechanism controlling the dynamic production of fusion-competent infectious virus particles during the viral life cycle. We explored the biological role of a newly identified furin-directed human microRNA, miR-24, in this process as a potential post-transcriptional regulator of the furin-mediated activation of HA0 and production of fusion-competent virions in the host secretory pathway. We report that miR-24 and furin are differentially expressed in human A549 cells infected with HP avian-origin infA H5N1. Using miR-24 mimics, we demonstrated a robust decrease in both furin mRNA levels and intracellular furin activity in A549 cells. Importantly, pretreatment of A549 cells with miR-24 mimicked these results: a robust decrease of H5N1 infectious virions and a complete block of H5N1 virus spread that was not observed in A549 cells infected with low-pathogenicity swine-origin infA H1N1 virus. Our results suggest that viral-specific downregulation of furin-directed microRNAs such as miR-24 during the life cycle of HP infA viruses may represent a novel regulatory mechanism that governs furin-mediated proteolytic activation of HA0 glycoproteins and production of infectious virions.

  2. Pathogenic human viruses in coastal waters

    USGS Publications Warehouse

    Griffin, Dale W.; Donaldson, Kim A.; Paul, J.H.; Rose, Joan B.

    2003-01-01

    This review addresses both historical and recent investigations into viral contamination of marine waters. With the relatively recent emergence of molecular biology-based assays, a number of investigations have shown that pathogenic viruses are prevalent in marine waters being impacted by sewage. Research has shown that this group of fecal-oral viral pathogens (enteroviruses, hepatitis A viruses, Norwalk viruses, reoviruses, adenoviruses, rotaviruses, etc.) can cause a broad range of asymptomatic to severe gastrointestinal, respiratory, and eye, nose, ear, and skin infections in people exposed through recreational use of the water. The viruses and the nucleic acid signature survive for an extended period in the marine environment. One of the primary concerns of public health officials is the relationship between the presence of pathogens and the recreational risk to human health in polluted marine environments. While a number of studies have attempted to address this issue, the relationship is still poorly understood. A contributing factor to our lack of progress in the field has been the lack of sensitive methods to detect the broad range of both bacterial and viral pathogens. The application of new and advanced molecular methods will continue to contribute to our current state of knowledge in this emerging and

  3. Reduced experimental infectivity and transmissibility of intercontinental H5 (H5N8 and H5N2) compared to Eurasian H5N1 highly pathogenic avian influenza viruses for chickens, turkeys, and Japanese quail

    Technology Transfer Automated Retrieval System (TEKTRAN)

    H5N1 high pathogenicity avian influenza (HPAI) virus (HPAIV) emerged in 1996 in Guangdong China and has since spread to infect and cause deaths in wild birds, poultry and humans in over 63 countries in Asia, Europe and Africa; and more recently a reassortant H5N8 clade 2.3.4.4 HPAI virus has spread ...

  4. Improved Pathogenicity of a Beet Black Scorch Virus Variant by Low Temperature and Co-infection with Its Satellite RNA

    PubMed Central

    Xu, Jin; Liu, Deshui; Zhang, Yongliang; Wang, Ying; Han, Chenggui; Li, Dawei; Yu, Jia-Lin; Wang, Xian-Bing

    2016-01-01

    Co-infection of none-coding satellite RNAs (sat-RNAs) usually inhibits replication and attenuates disease symptoms of helper viruses. However, we find that the sat-RNA of Beet black scorch virus (BBSV) and low temperature (18°C) additively enhance the systemic infection of BBSV in Nicotiana benthamiana. Northern blotting hybridization revealed a relatively reduced accumulation of BBSV-derived small interfering RNAs (siRNAs) in presence of sat-RNA as compared to that of BBSV alone. Cloning and sequencing of total small RNAs showed that more than 50% of the total small RNAs sequenced from BBSV-infected plants were BBSV-siRNAs, whereas the abundance of sat-siRNAs were higher than BBSV-siRNAs in the sat-RNA co-infected plants, indicating that the sat-RNA occupies most of the silencing components and possibly relieves the RNA silencing-mediated defense against BBSV. Interestingly, the 5′ termini of siRNAs derived from BBSV and sat-RNA were dominated by Uridines (U) and Adenines (A), respectively. Besides, the infection of BBSV alone and with sat-RNA induce down-regulation of miR168 and miR403, respectively, which leads to high accumulation of their targets, Argonaute 1 (AGO1) and AGO2. Our work reveals the profiles of siRNAs of BBSV and sat-RNA and provides an additional clue to investigate the complicated interaction between the helper virus and sat-RNA. PMID:27867378

  5. Differential host gene expression in cells infected with highly pathogenic H5N1 avian influenza viruses.

    PubMed

    Sarmento, Luciana; Afonso, Claudio L; Estevez, Carlos; Wasilenko, Jamie; Pantin-Jackwood, Mary

    2008-10-15

    In order to understand the molecular mechanisms by which different strains of avian influenza viruses overcome host response in birds, we used a complete chicken genome microarray to compare early gene expression levels in chicken embryo fibroblasts (CEF) infected with two avian influenza viruses (AIV), A/CK/Hong Kong/220/97 and A/Egret/Hong Kong/757.2/02, with different replication characteristics. Gene ontology revealed that the genes with altered expression are involved in many vital functional classes including protein metabolism, translation, transcription, host defense/immune response, ubiquitination and the cell cycle. Among the immune-related genes, MEK2, MHC class I, PDCD10 and Bcl-3 were selected for further expression analysis at 24 hpi using semi-quantitive RT-PCR. Infection of CEF with A/Egret/Hong Kong/757.2/02 resulted in a marked repression of MEK2 and MHC class I gene expression levels. Infection of CEF with A/CK/Hong Kong/220/97 induced an increase of MEK2 and a decrease in PDCD10 and Bcl-3 expression levels. The expression levels of alpha interferon (IFN-alpha), myxovirus resistance 1 (Mx1) and interleukin-8 (IL-8) were also analyzed at 24 hpi, showing higher expression levels of all of these genes after infection with A/CK/Hong Kong/220/97 compared to A/Egret/Hong Kong/757.2/02. In addition, comparison of the NS1 sequences of the viruses revealed amino acid differences that may explain in part the differences in IFN-alpha expression observed. Microarray gene expression analysis has proven to be a useful tool on providing important insights into how different AIVs affect host gene expression and how AIVs may use different strategies to evade host response and replicate in host cells.

  6. Effect of porcine circovirus type 2a or 2b on infection kinetics and pathogenicity of two genetically divergent strains of porcine reproductive and respiratory syndrome virus in the conventional pig model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to characterize the infection dynamics and pathogenicity of two heterologous type 2 porcine reproductive and respiratory syndrome virus (PRRSV) isolates in a conventional pig model under the influence of concurrent porcine circovirus (PCV) subtype 2a or 2b infection. ...

  7. Zika Virus as an Emerging Global Pathogen

    PubMed Central

    Beckham, J. David; Pastula, Daniel M.; Massey, Aaron; Tyler, Kenneth L.

    2016-01-01

    IMPORTANCE Zika virus (ZIKV) is an emerging arthropod-borne virus (arbovirus) in the genus Flavivirus that has caused a widespread outbreak of febrile illness, is associated with neurological disease, and has spread across the Pacific to the Americas in a short period. OBSERVATIONS In this review, we discuss what is currently known about ZIKV, neuroimmunologic complications, and the impact on global human health. Zika virus spread across Africa and Asia in part owing to unique genomic evolutionary conditions and pressures resulting in specific human disease manifestations, complications, and pathogenesis. Recent data suggest that acute ZIKV infection in pregnant women may result in acute infection of fetal tissue and brain tissue, causing microcephaly and potentially severe debilitation of the infant or even death of the fetus. Cases of acute ZIKV are also associated with Guillain-Barré syndrome. With the increased number of cases, new complications such as ocular involvement and sexual transmission have been reported. CONCLUSIONS AND RELEVANCE Zika virus is an emerging viral pathogen with significant consequences on human health throughout the world. Ongoing research into this pathogen is urgently needed to produce viable vaccine and therapeutic options. PMID:27183312

  8. A comparative evaluation of feathers, oropharyngeal swabs, and cloacal swabs for the detection of H5N1 highly pathogenic avian influenza virus infection in experimentally infected chickens and ducks.

    PubMed

    Nuradji, Harimurti; Bingham, John; Lowther, Sue; Wibawa, Hendra; Colling, Axel; Long, Ngo Thanh; Meers, Joanne

    2015-11-01

    Oropharyngeal and cloacal swabs have been widely used for the detection of H5N1 highly pathogenic avian Influenza A virus (HPAI virus) in birds. Previous studies have shown that the feather calamus is a site of H5N1 virus replication and therefore has potential for diagnosis of avian influenza. However, studies characterizing the value of feathers for this purpose are not available, to our knowledge; herein we present a study investigating feathers for detection of H5N1 virus. Ducks and chickens were experimentally infected with H5N1 HPAI virus belonging to 1 of 3 clades (Indonesian clades 2.1.1 and 2.1.3, Vietnamese clade 1). Different types of feathers and oropharyngeal and cloacal swab samples were compared by virus isolation. In chickens, virus was detected from all sample types: oral and cloacal swabs, and immature pectorosternal, flight, and tail feathers. During clinical disease, the viral titers were higher in feathers than swabs. In ducks, the proportion of virus-positive samples was variable depending on viral strain and time from challenge; cloacal swabs and mature pectorosternal feathers were clearly inferior to oral swabs and immature pectorosternal, tail, and flight feathers. In ducks infected with Indonesian strains, in which most birds did not develop clinical signs, all sampling methods gave intermittent positive results; 3-23% of immature pectorosternal feathers were positive during the acute infection period; oropharyngeal swabs had slightly higher positivity during early infection, while feathers performed better during late infection. Our results indicate that immature feathers are an alternative sample for the diagnosis of HPAI in chickens and ducks.

  9. Experimental infection of a North American raptor, American Kestrel (Falco sparverius), with highly pathogenic avian influenza virus (H5N1).

    PubMed

    Hall, Jeffrey S; Ip, Hon S; Franson, J Christian; Meteyer, Carol; Nashold, Sean; TeSlaa, Joshua L; French, John; Redig, Patrick; Brand, Christopher

    2009-10-22

    Several species of wild raptors have been found in Eurasia infected with highly pathogenic avian influenza virus (HPAIV) subtype H5N1. Should HPAIV (H5N1) reach North America in migratory birds, species of raptors are at risk not only from environmental exposure, but also from consuming infected birds and carcasses. In this study we used American kestrels as a representative species of a North American raptor to examine the effects of HPAIV (H5N1) infection in terms of dose response, viral shedding, pathology, and survival. Our data showed that kestrels are highly susceptible to HPAIV (H5N1). All birds typically died or were euthanized due to severe neurologic disease within 4-5 days of inoculation and shed significant amounts of virus both orally and cloacally, regardless of dose administered. The most consistent microscopic lesions were necrosis in the brain and pancreas. This is the first experimental study of HPAIV infection in a North American raptor and highlights the potential risks to birds of prey if HPAIV (H5N1) is introduced into North America.

  10. Experimental infection of a North American raptor, American kestrel (Falco sparverius), with highly pathogenic avian influenza virus (H5N1)

    USGS Publications Warehouse

    Hall, J.S.; Ip, H.S.; Franson, J.C.; Meteyer, C.; Nashold, S.; Teslaa, J.L.; French, J.; Redig, P.; Brand, C.

    2009-01-01

    Several species of wild raptors have been found in Eurasia infected with highly pathogenic avian influenza virus (HPAIV) subtype H5N1. Should HPAIV (H5N1) reach North America in migratory birds, species of raptors are at risk not only from environmental exposure, but also from consuming infected birds and carcasses. In this study we used American kestrels as a representative species of a North American raptor to examine the effects of HPAIV (H5N1) infection in terms of dose response, viral shedding, pathology, and survival. Our data showed that kestrels are highly susceptible to HPAIV (H5N1). All birds typically died or were euthanized due to severe neurologic disease within 4-5 days of inoculation and shed significant amounts of virus both orally and cloacally, regardless of dose administered. The most consistent microscopic lesions were necrosis in the brain and pancreas. This is the first experimental study of HPAIV infection in a North American raptor and highlights the potential risks to birds of prey if HPAIV (H5N1) is introduced into North America.

  11. Serologic cross-reactivity among humans and birds infected with highly pathogenic avian influenza A subtype H5N1 viruses in China.

    PubMed

    Li, Zheng; Ma, Chi; Liu, Zhonghua; He, Wei

    2011-03-30

    To study immunogenicity and serologic cross-reactivity of hemagglutinins (HAs) among humans and birds infected with highly pathogenic avian influenza (HPAI) H5N1, four representative H5N1 HA genes from humans and birds infected with distinct genetic clusters of H5N1 viruses in China were cloned, and several H5N1 infected human serum and H5N1 positive bird serum samples were used. Recombinant HA proteins were generated for ELISA assays and pseudotype viruses containing HAs were produced for neutralization assays and hemagglutination inhibition (HI) tests. We found significant differences among clades compared to species in binding, neutralization and HI activity of H5N1 strains isolated from birds. While significant differences were observed among species in H5N1 isolated from humans, investigation of H5N1 infected human and avian sera provided evidence that the pressure from nAb may be a driving force for positive selection. Therefore, improved anti-viral nAb therapies could block avian influenza transmission in humans.

  12. 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.

  13. Risk Reduction Modeling of High Pathogenicity Avian Influenza Virus Titers in Nonpasteurized Liquid Egg Obtained from Infected but Undetected Chicken Flocks.

    PubMed

    Weaver, J Todd; Malladi, Sasidhar; Spackman, Erica; Swayne, David E

    2015-11-01

    Control of highly pathogenic avian influenza (HPAI) outbreaks in poultry has traditionally involved the establishment of disease containment zones, where poultry products are only permitted to move from within a zone under permit. Nonpasteurized liquid egg (NPLE) is one such commodity for which movements may be permitted, considering inactivation of HPAI virus via pasteurization. Active surveillance testing at the flock level, using targeted matrix gene real-time reversed transcriptase-polymerase chain reaction testing (RRT-PCR) has been incorporated into HPAI emergency response plans as the primary on-farm diagnostic test procedure to detect HPAI in poultry and is considered to be a key risk mitigation measure. To inform decisions regarding the potential movement of NPLE to a pasteurization facility, average HPAI virus concentrations in NPLE produced from a HPAI virus infected, but undetected, commercial table-egg-layer flock were estimated for three HPAI virus strains using quantitative simulation models. Pasteurization under newly proposed international design standards (5 log10 reduction) is predicted to inactivate HPAI virus in NPLE to a very low concentration of less than 1 embryo infectious dose (EID)50 /mL, considering the predicted virus titers in NPLE from a table-egg flock under active surveillance. Dilution of HPAI virus from contaminated eggs in eggs from the same flock, and in a 40,000 lb tanker-truck load of NPLE containing eggs from disease-free flocks was also considered. Risk assessment can be useful in the evaluation of commodity-specific risk mitigation measures to facilitate safe trade in animal products from countries experiencing outbreaks of highly transmissible animal diseases.

  14. INFLAMMATORY EFFECTS OF HIGHLY PATHOGENIC H5N1 INFLUENZA VIRUS INFECTION IN THE CNS OF MICE

    PubMed Central

    Jang, Haeman; Boltz, David; McClaren, Jennifer; Pani, Amar K.; Smeyne, Michelle; Korff, Ane; Webster, Robert; Smeyne, Richard Jay

    2012-01-01

    The A/VN/1203/04 H5N1 influenza virus is capable of infecting the CNS of mice and inducing a number of neurodegenerative pathologies. Here, we examined the effects of H5N1 on several pathological aspects affected in parkinsonism, including loss of the phenotype of dopaminergic (DAergic) neurons located in the substantia nigra pars compacta (SNpc), expression of mono- and indolamines in brain, alterations in SNpc microglia number and morphology, and expression of cytokines, chemokines and growth factors. We find that H5N1 induces a transient loss of the DAergic phenotype in SNpc and now report that this loss recovers by 90 days post infection (dpi). A similar pattern of loss and recovery was seen in monoamine levels of the basal ganglia. The inflammatory response in lung and different regions of the brain known to be targets of the H5N1 virus (brainstem, substantia nigra, striatum, and cortex) were examined at 3, 10, 21, 60 and 90 dpi. We found a significant increase in the number of activated microglia in each of these brain regions that lasted at least 90 days. We also quantified expression of IL-1α, IL-1β, IL-2, IL-6, IL-9, IL-10, IL-12(p70), IL-13, TNF-α, IFN-γ, GM-CSF, G-CSF, M-CSF, eotaxin, IP-10, KC, MCP-1, MIP-1α, MIP-1β and VEGF and find that the pattern and levels of expression are dependent on both brain region and time after infection. We conclude that H5N1 infection in mice induces a long-lasting inflammatory response in brain and may play a contributing factor in the development of pathologies in neurodegenerative disorders. PMID:22302798

  15. Effect of age on pathogenesis and innate immune responses in Pekin ducks infected with different H5N1 highly pathogenic avian influenza viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The pathogenicity of H5N1 highly pathogenic avian influenza (HPAI) viruses in domestic ducks varies between different viruses and is affected by the age of the ducks, with younger ducks presenting more severe disease. In order to better understand the pathobiology of H5N1 HPAI in ducks, including t...

  16. A parvo-like virus persistently infecting a C6/36 clone of Aedes albopictus mosquito cell line and pathogenic for Aedes aegypti larvae.

    PubMed

    Jousset, F X; Barreau, C; Boublik, Y; Cornet, M

    1993-08-01

    We have isolated and partially characterized from an apparently healthy C6/36 subclone of Aedes albopictus cell line a small icosahedral non-enveloped DNA virus, designated AaPV. This virus proved to be highly pathogenic for Aedes aegypti neonate larvae. Viral infection persisted for over 4 years in the cell culture without any cytopathic effect. Attempts to infect suckling mice, Drosophila melanogaster adults and Spodoptera littoralis larvae with AaPV were unsuccessful. Similarly, the AaPV failed to replicate in vertebrate and Drosophila cell lines. Virions, about 22 nm in diameter, had a buoyant density of 1.43 g/cm3 and contained three capsid polypeptides with molecular weights of 53, 41 and 40 kDa. A preliminary study of the viral genome indicated the presence of single-stranded DNA. By its biophysical and biochemical properties, this virus appears to be related to the genus Densovirus within the family Parvoviridae, but lacks serological relationships with the other members of this genus.

  17. Transcription analysis on response of porcine alveolar macrophages to co-infection of the highly pathogenic porcine reproductive and respiratory syndrome virus and Mycoplasma hyopneumoniae.

    PubMed

    Li, Bin; Du, Luping; Xu, Xiangwei; Sun, Bing; Yu, Zhengyu; Feng, Zhixin; Liu, Maojun; Wei, Yanna; Wang, Haiyan; Shao, Guoqing; He, Kongwang

    2015-01-22

    Porcine respiratory disease complex (PRDC) is of great concern economically, for swine producers worldwide. Co-infections with porcine reproductive and respiratory syndrome virus (PRRSV) and Mycoplasma hyopneumoniae (Mhp) are considered the major causative agents of PRDC, and responsible for mass mortality in pigs. Nevertheless, the molecular mechanisms underlying the host factors involved in pathogenesis and persistent infection have not been clearly established because of a lack of information regarding host responses following co-infection. In the current study, high throughput cDNA microarray assays were employed to evaluate host responses of porcine alveolar macrophages (PAM) to co-infection with highly pathogenic PRRSV (HP-PRRSV) and Mhp. A total of 2152 and 1760 genes were identified as being differentially expressed between the control group and PRRSV+Mhp co-infected group at 6 and 15 h post infection, respectively. The DE genes were involved in many vital functional classes, including inflammatory response, immune response, apoptosis, defense response, signal transduction. The pathway analysis demonstrated that the most significant pathways were associated with chemokine signaling pathway, cytokine, TLR, RLR and NLR signaling pathways and Jak-STAT signaling pathway. STRING analysis demonstrated that IL-1β is an integral gene in co-infections with PRRSV and Mhp. The present study is the first to document the response of PAMs to co-infection with HP-PRRSV and Mhp. The observed gene expression profile could help with the screening of potential host agents for reducing the prevalence of co-infections, and to further develop our understanding of the molecular pathogenesis associated with PRRSV and Mhp co-infection in pigs.

  18. Infectivity, transmission and pathogenicity of H5 highly pathogenic avian influenza clade 2.3.4.4 (H5N8 and H5N2) United States index viruses in Pekin ducks and Chinese geese

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In late 2014, a H5N8 highly pathogenic avian influenza (HPAI) virus, clade 2.3.4.4, spread by migratory birds into North America mixing with low pathogenicity AI viruses to produce a H5N2 HPAI virus. The H5N8 and H5N2 HPAI viruses were detected initially in wild waterfowl and backyard birds, and lat...

  19. Combinations of Oseltamivir and T-705 Extend the Treatment Window for Highly Pathogenic Influenza A(H5N1) Virus Infection in Mice.

    PubMed

    Marathe, Bindumadhav M; Wong, Sook-San; Vogel, Peter; Garcia-Alcalde, Fernando; Webster, Robert G; Webby, Richard J; Najera, Isabel; Govorkova, Elena A

    2016-05-25

    Current anti-influenza therapy depends on administering drugs soon after infection, which is often impractical. We assessed whether combinations of oseltamivir (a neuraminidase inhibitor) and T-705 (a nonspecific inhibitor of viral polymerases) could extend the window for treating lethal infection with highly pathogenic A(H5N1) influenza virus in mice. Combination therapy protected 100% of mice, even when delayed until 96 h postinoculation. Compared to animals receiving monotherapy, mice receiving combination therapy had reduced viral loads and restricted viral spread in lung tissues, limited lung damage, and decreased inflammatory cytokine production. Next-generation sequencing showed that virus populations in T-705-treated mice had greater genetic variability, with more frequent transversion events, than did populations in control and oseltamivir-treated mice, but no substitutions associated with resistance to oseltamivir or T-705 were detected. Thus, combination therapy extended the treatment window for A(H5N1) influenza infection in mice and should be considered for evaluation in a clinical setting.

  20. Combinations of Oseltamivir and T-705 Extend the Treatment Window for Highly Pathogenic Influenza A(H5N1) Virus Infection in Mice

    PubMed Central

    Marathe, Bindumadhav M.; Wong, Sook-San; Vogel, Peter; Garcia-Alcalde, Fernando; Webster, Robert G.; Webby, Richard J.; Najera, Isabel; Govorkova, Elena A.

    2016-01-01

    Current anti-influenza therapy depends on administering drugs soon after infection, which is often impractical. We assessed whether combinations of oseltamivir (a neuraminidase inhibitor) and T-705 (a nonspecific inhibitor of viral polymerases) could extend the window for treating lethal infection with highly pathogenic A(H5N1) influenza virus in mice. Combination therapy protected 100% of mice, even when delayed until 96 h postinoculation. Compared to animals receiving monotherapy, mice receiving combination therapy had reduced viral loads and restricted viral spread in lung tissues, limited lung damage, and decreased inflammatory cytokine production. Next-generation sequencing showed that virus populations in T-705–treated mice had greater genetic variability, with more frequent transversion events, than did populations in control and oseltamivir-treated mice, but no substitutions associated with resistance to oseltamivir or T-705 were detected. Thus, combination therapy extended the treatment window for A(H5N1) influenza infection in mice and should be considered for evaluation in a clinical setting. PMID:27221530

  1. Systems analysis of immune responses in Marek's disease virus-infected chickens identifies a gene involved in susceptibility and highlights a possible novel pathogenicity mechanism.

    PubMed

    Smith, Jacqueline; Sadeyen, Jean-Remy; Paton, Ian R; Hocking, Paul M; Salmon, Nigel; Fife, Mark; Nair, Venugopal; Burt, David W; Kaiser, Pete

    2011-11-01

    Marek's disease virus (MDV) is a highly contagious oncogenic alphaherpesvirus that causes disease that is both a cancer model and a continuing threat to the world's poultry industry. This comprehensive gene expression study analyzes the host response to infection in both resistant and susceptible lines of chickens and inherent expression differences between the two lines following the infection of the host. A novel pathogenicity mechanism, involving the downregulation of genes containing HIC1 transcription factor binding sites as early as 4 days postinfection, was suggested from this analysis. HIC1 drives antitumor mechanisms, suggesting that MDV infection switches off genes involved in antitumor regulation several days before the expression of the MDV oncogene meq. The comparison of the gene expression data to previous QTL data identified several genes as candidates for involvement in resistance to MD. One of these genes, IRG1, was confirmed by single nucleotide polymorphism analysis to be involved in susceptibility. Its precise mechanism remains to be elucidated, although the analysis of gene expression data suggests it has a role in apoptosis. Understanding which genes are involved in susceptibility/resistance to MD and defining the pathological mechanisms of the disease gives us a much greater ability to try to reduce the incidence of this virus, which is costly to the poultry industry in terms of both animal welfare and economics.

  2. Impact of vaccination on infection with Vietnam H5N1 high pathogenicity avian influenza virus in hens and the eggs they lay.

    PubMed

    Bertran, Kateri; Moresco, Kira; Swayne, David E

    2015-03-10

    High pathogenicity avian influenza virus (HPAIV) infections in chickens negatively impact egg production and cause egg contamination. Previously, vaccination maintained egg production and reduced egg contamination when challenged with a North American H5N2 HPAIV. However, Asian H5N1 HPAIV infection has some characteristics of increased pathogenicity compared to other H5 HPAIV such as more rapid drop and complete cessation in egg production. Sham (vaccinated at 25 and 28 weeks of age), inactivated H5N1 Once (1X-H5-Vax; vaccinated at 28 weeks of age only) and inactivated H5N1 Twice (2X-H5-Vax; vaccinated at 25 and 28 weeks of age) vaccinated adult White Leghorn hens were challenged intranasally at 31 weeks of age with 6.1 log10 mean embryo infectious doses (EID50) of clade 2.3.2.1a H5N1 HPAIV (A/chicken/Vietnam/NCVD-675/2011) which was homologous to the inactivated vaccine. Sham-vaccinated layers experienced 100% mortality within 3 days post-challenge; laid soft and thin-shelled eggs; had recovery of virus from oral swabs and in 53% of the eggs from eggshell surface (35%), yolk (24%), and albumin (41%); and had very high titers of virus (average 7.91 log10 EID50/g) in all segments of the oviduct and ovary. By comparison, 1X- and 2X-H5-Vax challenged hens survived infection, laid similar number of eggs pre- and post-challenge, all eggs had normal egg shell quality, and had significantly fewer contaminated eggs with reduced virus quantity. The 2X-H5-Vax hens had significantly higher HI titers by the day of challenge (304 GMT) and at termination (512 GMT) than 1X-H5-Vax hens (45 GMT and 128 GMT). The current study demonstrated that AIV infections caused by clade 2.3.2.1a H5N1 variants can be effectively controlled by either double or single homologous vaccination.

  3. Recombinant feline leukemia virus (FeLV) variants establish a limited infection with altered cell tropism in specific-pathogen-free cats in the absence of FeLV subgroup A helper virus.

    PubMed

    Bechtel, M K; Hayes, K A; Mathes, L E; Pandey, R; Stromberg, P C; Roy-Burman, P

    1999-03-01

    Feline leukemia virus subgroup B (FeLV-B) is commonly associated with feline lymphosarcoma and arises through recombination between endogenous retroviral elements inherited in the cat genome and corresponding regions of the envelope (env) gene from FeLV subgroup A (FeLV-A). In vivo infectivity for FeLV-B is thought to be inefficient in the absence of FeLV-A. Proposed FeLV-A helper functions include enhanced replication efficiency, immune evasion, and replication rescue for defective FeLV-B virions. In vitro analysis of the recombinant FeLV-B-like viruses (rFeLVs) employed in this study confirmed these viruses were replication competent prior to their use in an in vivo study without FeLV-A helper virus. Eight specific-pathogen-free kittens were inoculated with the rFeLVs alone. Subsequent hematology and histology results were within normal limits, however, in the absence of detectable viremia, virus expression, or significant seroconversion, rFeLV proviral DNA was detected in bone marrow tissue of 4/4 (100%) cats at 45 weeks postinoculation (pi), indicating these rFeLVs established a limited but persistent infection in the absence of FeLV-A. Altered cell tropism was also noted. Focal infection was seen in T-cell areas of the splenic follicles in 3/4 (75%) rFeLV-infected cats analyzed, while an FeLV-A-infected cat showed focal infection in B-cell areas of the splenic follicles. Nucleotide sequence analysis of the surface glycoprotein portion of the rFeLV env gene amplified from bone marrow tissue collected at 45 weeks pi showed no sequence alterations from the original rFeLV inocula.

  4. 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

  5. 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.

  6. [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.

  7. Highly pathogenic avian influenza virus H5N1 infection in a long-distance migrant shorebird under migratory and non-migratory states.

    PubMed

    Reperant, Leslie A; van de Bildt, Marco W G; van Amerongen, Geert; Buehler, Debbie M; Osterhaus, Albert D M E; Jenni-Eiermann, Susi; Piersma, Theunis; Kuiken, Thijs

    2011-01-01

    Corticosterone regulates physiological changes preparing wild birds for migration. It also modulates the immune system and may lead to increased susceptibility to infection, with implications for the spread of pathogens, including highly pathogenic avian influenza virus (HPAIV) H5N1. The red knot (Calidris canutus islandica) displays migratory changes in captivity and was used as a model to assess the effect of high plasma concentration of corticosterone on HPAIV H5N1 infection. We inoculated knots during pre-migration (N = 6), fueling (N = 5), migration (N = 9) and post-migration periods (N = 6). Knots from all groups shed similar viral titers for up to 5 days post-inoculation (dpi), peaking at 1 to 3 dpi. Lesions of acute encephalitis, associated with virus replication in neurons, were seen in 1 to 2 knots per group, leading to neurological disease and death at 5 to 11 dpi. Therefore, the risk of HPAIV H5N1 infection in wild birds and of potential transmission between wild birds and poultry may be similar at different times of the year, irrespective of wild birds' migratory status. However, in knots inoculated during the migration period, viral shedding levels positively correlated with pre-inoculation plasma concentration of corticosterone. Of these, knots that did not become productively infected had lower plasma concentration of corticosterone. Conversely, elevated plasma concentration of corticosterone did not result in an increased probability to develop clinical disease. These results suggest that birds with elevated plasma concentration of corticosterone at the time of migration (ready to migrate) may be more susceptible to acquisition of infection and shed higher viral titers--before the onset of clinical disease--than birds with low concentration of corticosterone (not ready for take-off). Yet, they may not be more prone to the development of clinical disease. Therefore, assuming no effect of sub-clinical infection on the likelihood of

  8. Highly Pathogenic Avian Influenza Virus H5N1 Infection in a Long-Distance Migrant Shorebird under Migratory and Non-Migratory States

    PubMed Central

    Reperant, Leslie A.; van de Bildt, Marco W. G.; van Amerongen, Geert; Buehler, Debbie M.; Osterhaus, Albert D. M. E.; Jenni-Eiermann, Susi; Piersma, Theunis; Kuiken, Thijs

    2011-01-01

    Corticosterone regulates physiological changes preparing wild birds for migration. It also modulates the immune system and may lead to increased susceptibility to infection, with implications for the spread of pathogens, including highly pathogenic avian influenza virus (HPAIV) H5N1. The red knot (Calidris canutus islandica) displays migratory changes in captivity and was used as a model to assess the effect of high plasma concentration of corticosterone on HPAIV H5N1 infection. We inoculated knots during pre-migration (N = 6), fueling (N = 5), migration (N = 9) and post-migration periods (N = 6). Knots from all groups shed similar viral titers for up to 5 days post-inoculation (dpi), peaking at 1 to 3 dpi. Lesions of acute encephalitis, associated with virus replication in neurons, were seen in 1 to 2 knots per group, leading to neurological disease and death at 5 to 11 dpi. Therefore, the risk of HPAIV H5N1 infection in wild birds and of potential transmission between wild birds and poultry may be similar at different times of the year, irrespective of wild birds' migratory status. However, in knots inoculated during the migration period, viral shedding levels positively correlated with pre-inoculation plasma concentration of corticosterone. Of these, knots that did not become productively infected had lower plasma concentration of corticosterone. Conversely, elevated plasma concentration of corticosterone did not result in an increased probability to develop clinical disease. These results suggest that birds with elevated plasma concentration of corticosterone at the time of migration (ready to migrate) may be more susceptible to acquisition of infection and shed higher viral titers—before the onset of clinical disease—than birds with low concentration of corticosterone (not ready for take-off). Yet, they may not be more prone to the development of clinical disease. Therefore, assuming no effect of sub-clinical infection on the likelihood of

  9. A soluble envelope protein of endogenous retrovirus (FeLIX) present in serum of domestic cats mediates infection of a pathogenic variant of feline leukemia virus.

    PubMed

    Sakaguchi, Shoichi; Shojima, Takayuki; Fukui, Daisuke; Miyazawa, Takayuki

    2015-03-01

    T-lymphotropic feline leukemia virus (FeLV-T), a highly pathogenic variant of FeLV, induces severe immunosuppression in cats. FeLV-T is fusion defective because in its PHQ motif, a gammaretroviral consensus motif in the N terminus of an envelope protein, histidine is replaced with aspartate. Infection by FeLV-T requires FeLIX, a truncated envelope protein encoded by an endogenous FeLV, for transactivation of infectivity and Pit1 for binding FeLIX. Although Pit1 is present in most tissues in cats, the expression of FeLIX is limited to certain cells in lymphoid organs. Therefore, the host cell range of FeLV-T was thought to be restricted to cells expressing FeLIX. However, because FeLIX is a soluble factor and is expressed constitutively in lymphoid organs, we presumed it to be present in blood and evaluated its activities in sera of various mammalian species using a pseudotype assay. We demonstrated that cat serum has FeLIX activity at a functional level, suggesting that FeLIX is present in the blood and that FeLV-T may be able to infect cells expressing Pit1 regardless of the expression of FeLIX in vivo. In addition, FeLIX activities in sera were detected only in domestic cats and not in other feline species tested. To our knowledge, this is the first report to prove that a large amount of truncated envelope protein of endogenous retrovirus is circulating in the blood to facilitate the infection of a pathogenic exogenous retrovirus.

  10. Waterborne human pathogenic viruses of public health concern.

    PubMed

    Ganesh, Atheesha; Lin, Johnson

    2013-12-01

    In recent years, the impending impact of waterborne pathogens on human health has become a growing concern. Drinking water and recreational exposure to polluted water have shown to be linked to viral infections, since viruses are shed in extremely high numbers in the faeces and vomit of infected individuals and are routinely introduced into the water environment. All of the identified pathogenic viruses that pose a significant public health threat in the water environment are transmitted via the faecal-oral route. This group, are collectively known as enteric viruses, and their possible health effects include gastroenteritis, paralysis, meningitis, hepatitis, respiratory illness and diarrhoea. This review addresses both past and recent investigations into viral contamination of surface waters, with emphasis on six types of potential waterborne human pathogenic viruses. In addition, the viral associated illnesses are outlined with reference to their pathogenesis and routes of transmission.

  11. Efficacy of single dose of a bivalent vaccine containing inactivated Newcastle disease virus and reassortant highly pathogenic avian influenza H5N1 virus against lethal HPAI and NDV infection in chickens.

    PubMed

    Lee, Dong-Hun; Park, Jae-Keun; Kwon, Jung-Hoon; Yuk, Seong-Su; Erdene-Ochir, Tseren-Ochir; Jang, Yo-Han; Seong, Baik-Lin; Lee, Joong-Bok; Park, Seung-Yong; Choi, In-Soo; Song, Chang-Seon

    2013-01-01

    Highly pathogenic avian influenza (HPAI) and Newcastle disease (ND) are 2 devastating diseases of poultry, which cause great economic losses to the poultry industry. In the present study, we developed a bivalent vaccine containing antigens of inactivated ND and reassortant HPAI H5N1 viruses as a candidate poultry vaccine, and we evaluated its immunogenicity and protective efficacy in specific pathogen-free chickens. The 6:2 reassortant H5N1 vaccine strain containing the surface genes of the A/Chicken/Korea/ES/2003(H5N1) virus was successfully generated by reverse genetics. A polybasic cleavage site of the hemagglutinin segment was replaced by a monobasic cleavage site. We characterized the reverse genetics-derived reassortant HPAI H5N1 clade 2.5 vaccine strain by evaluating its growth kinetics in eggs, minimum effective dose in chickens, and cross-clade immunogenicity against HPAI clade 1 and 2. The bivalent vaccine was prepared by emulsifying inactivated ND (La Sota strain) and reassortant HPAI viruses with Montanide ISA 70 adjuvant. A single immunization with this vaccine induced high levels of hemagglutination-inhibiting antibody titers and protected chickens against a lethal challenge with the wild-type HPAI and ND viruses. Our results demonstrate that the bivalent, inactivated vaccine developed in this study is a promising approach for the control of both HPAI H5N1 and ND viral infections.

  12. In Vivo Monocyte Tropism of Pathogenic Feline Immunodeficiency Viruses

    PubMed Central

    Dow, Steven W.; Mathiason, Candace K.; Hoover, Edward A.

    1999-01-01

    Virus-infected monocytes rarely are detected in the bloodstreams of animals or people infected with immunodeficiency-inducing lentiviruses, yet tissue macrophages are thought to be a major reservoir of virus-infected cells in vivo. We have identified feline immunodeficiency virus (FIV) clinical isolates that are pathogenic in cats and readily transmitted vertically. We report here that five of these FIV isolates are highly monocytotropic in vivo. However, while FIV-infected monocytes were numerous in the blood of experimentally infected cats, viral antigen was not detectable in freshly isolated cells. Only after a short-term (at least 12-h) in vitro monocyte culture were FIV antigens detectable (by immunocytochemical analysis or enzyme-linked immunosorbent assay). In vitro experiments suggested that monocyte adherence provided an important trigger for virus antigen expression. In the blood of cats infected with a prototype monocytotropic isolate (FIV subtype B strain 2542), infected monocytes appeared within 2 weeks, correlating with high blood mononuclear-cell-associated viral titers and CD4 cell depletion. By contrast, infected monocytes could not be detected in the blood of cats infected with a less pathogenic FIV strain (FIV subtype A strain Petaluma). We concluded that some strains of FIV are monocytotropic in vivo. Moreover, this property may relate to virus virulence, vertical transmission, and infection of tissue macrophages. PMID:10400783

  13. Tobacco mosaic virus infection results in an increase in recombination frequency and resistance to viral, bacterial, and fungal pathogens in the progeny of infected tobacco plants.

    PubMed

    Kathiria, Palak; Sidler, Corinne; Golubov, Andrey; Kalischuk, Melanie; Kawchuk, Lawrence M; Kovalchuk, Igor

    2010-08-01

    Our previous experiments showed that infection of tobacco (Nicotiana tabacum) plants with Tobacco mosaic virus (TMV) leads to an increase in homologous recombination frequency (HRF). The progeny of infected plants also had an increased rate of rearrangements in resistance gene-like loci. Here, we report that tobacco plants infected with TMV exhibited an increase in HRF in two consecutive generations. Analysis of global genome methylation showed the hypermethylated genome in both generations of plants, whereas analysis of methylation via 5-methyl cytosine antibodies demonstrated both hypomethylation and hypermethylation. Analysis of the response of the progeny of infected plants to TMV, Pseudomonas syringae, or Phytophthora nicotianae revealed a significant delay in symptom development. Infection of these plants with TMV or P. syringae showed higher levels of induction of PATHOGENESIS-RELATED GENE1 gene expression and higher levels of callose deposition. Our experiments suggest that viral infection triggers specific changes in progeny that promote higher levels of HRF at the transgene and higher resistance to stress as compared with the progeny of unstressed plants. However, data reported in these studies do not establish evidence of a link between recombination frequency and stress resistance.

  14. Estimating the Per-Contact Probability of Infection by Highly Pathogenic Avian Influenza (H7N7) Virus during the 2003 Epidemic in The Netherlands

    PubMed Central

    Ssematimba, Amos; Elbers, Armin R. W.; Hagenaars, Thomas J.; de Jong, Mart C. M.

    2012-01-01

    Estimates of the per-contact probability of transmission between farms of Highly Pathogenic Avian Influenza virus of H7N7 subtype during the 2003 epidemic in the Netherlands are important for the design of better control and biosecurity strategies. We used standardized data collected during the epidemic and a model to extract data for untraced contacts based on the daily number of infectious farms within a given distance of a susceptible farm. With these data, we used a maximum likelihood estimation approach to estimate the transmission probabilities by the individual contact types, both traced and untraced. The estimated conditional probabilities, conditional on the contact originating from an infectious farm, of virus transmission were: 0.000057 per infectious farm within 1 km per day, 0.000413 per infectious farm between 1 and 3 km per day, 0.0000895 per infectious farm between 3 and 10 km per day, 0.0011 per crisis organisation contact, 0.0414 per feed delivery contact, 0.308 per egg transport contact, 0.133 per other-professional contact and, 0.246 per rendering contact. We validate these outcomes against literature data on virus genetic sequences for outbreak farms. These estimates can be used to inform further studies on the role that improved biosecurity between contacts and/or contact frequency reduction can play in eliminating between-farm spread of the virus during future epidemics. The findings also highlight the need to; 1) understand the routes underlying the infections without traced contacts and, 2) to review whether the contact-tracing protocol is exhaustive in relation to all the farm’s day-to-day activities and practices. PMID:22808285

  15. Using mean infectious dose of wild duck-and poultry-origin high and low pathogenicity avian influenza viruses as one measure of infectivity and adaptation to poultry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mean infectious doses of selected avian influenza virus (AIV) isolates, determined in domestic poultry under experimental conditions, were shown to be both host and virus dependent and could be considered one measure of the infectivity and adaptation to a specific host. As such, the mean infect...

  16. Detecting the emergence of novel, zoonotic viruses pathogenic to humans.

    PubMed

    Rosenberg, Ronald

    2015-03-01

    RNA viruses, with their high potential for mutation and epidemic spread, are the most common class of pathogens found as new causes of human illness. Despite great advances made in diagnostic technology since the 1950s, the annual rate at which novel virulent viruses have been found has remained at 2-3. Most emerging viruses are zoonoses; they have jumped from mammal or bird hosts to humans. An analysis of virus discovery indicates that the small number of novel viruses discovered annually is an artifact of inadequate surveillance in tropical and subtropical countries, where even established endemic pathogens are often misdiagnosed. Many of the emerging viruses of the future are already infecting humans but remain to be uncovered by a strategy of disease surveillance in selected populations.

  17. Detecting the emergence of novel, zoonotic viruses pathogenic to humans

    PubMed Central

    2015-01-01

    RNA viruses, with their high potential for mutation and epidemic spread, are the most common class of pathogens found as new causes of human illness. Despite great advances made in diagnostic technology since the 1950s, the annual rate at which novel virulent viruses have been found has remained at 2–3. Most emerging viruses are zoonoses; they have jumped from mammal or bird hosts to humans. An analysis of virus discovery indicates that the small number of novel viruses discovered annually is an artifact of inadequate surveillance in tropical and subtropical countries, where even established endemic pathogens are often misdiagnosed. Many of the emerging viruses of the future are already infecting humans but remain to be uncovered by a strategy of disease surveillance in selected populations. PMID:25416679

  18. Viruses - from pathogens to vaccine carriers.

    PubMed

    Small, Juliana C; Ertl, Hildegund C J

    2011-10-01

    Vaccination is mankind's greatest public health success story. By now vaccines to many of the viruses that once caused fatal childhood diseases are routinely used throughout the world. Traditional methods of vaccine development through inactivation or attenuation of viruses have failed for some of the most deadly human pathogens, necessitating new approaches. Genetic modification of viruses not only allows for their attenuation but also for incorporation of sequences from other viruses, turning one pathogen into a vaccine carrier for another. Recombinant viruses have pros and cons as vaccine carriers, as discussed below using vectors based on adenovirus, herpesvirus, flavivirus, and rhabdovirus as examples.

  19. [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.

  20. Eight-year observation and comparative study of specific pathogen-free cats experimentally infected with feline immunodeficiency virus (FIV) subtypes A and B: terminal acquired immunodeficiency syndrome in a cat infected with FIV petaluma strain.

    PubMed

    Kohmoto, M; Uetsuka, K; Ikeda, Y; Inoshima, Y; Shimojima, M; Sato, E; Inada, G; Toyosaki, T; Miyazawa, T; Doi, K; Mikami, T

    1998-03-01

    Three specific pathogen-free cats experimentally infected with feline immunodeficiency virus (FIV) strains Petaluma, TM1 and TM2, respectively were observed for over 8 years. Without showing any significant clinical signs of immunodeficiency syndrome (AIDS) for 8 years and 4 months of asymptomatic phase, the Petaluma-infected cat exhibited severe stomatitis/gingivitis, anorexia, emaciation, hematological and immunological disorders such as severe anemia, lymphopenia, thrombocytopenia, and decrease of CD4/CD8 ratio to 0.075, and finally died with hemoperitoneum at 8 years and 8 months post-infection. Histopathological studies revealed that the cat had systemic lymphoid atrophy and bone marrow disorders indicating acute myelocytic leukemia (aleukemic type). Plasma viral titer of the cat at AIDS phase was considerably high and anti-FIV antibody titer was slightly low as compared with the other FIV-infected cats. In addition, immunoblotting analysis using serially collected serum/plasma samples of these cats revealed that antibodies against FIV proteins were induced in all the infected cats, however in the Petaluma-infected cat anti-Gag antibodies disappeared during the asymptomatic period. These results suggested that plasma viral load and anti-FIV Gag antibody response correlated with disease progression, and supported FIV-infected cats as a suitable animal model of human AIDS.

  1. Pathogenic organisms in hip joint infections

    PubMed Central

    Geipel, Udo

    2009-01-01

    Infections of the hip joint are usually of bacterial etiology. Only rarely, an infectious arthritis is caused in this localization by viruses or fungi. Native joint infections of the hip are less common than infections after implantation of prosthetic devices. Difficulties in prosthetic joint infections are, (I) a higher age of patients, and, thus an associated presence of other medical risk factors, (II) often long courses of treatment regimes depending on the bacterium and its antibiotic resistance, (III) an increased mortality, and (IV) a high economic burden for removal and reimplantation of an infected prosthetic device. The pathogenic mechanisms responsible for articular infections are well studied only for some bacteria, e.g. Staphylococcus aureus, while others are only partially understood. Important known bacterial properties and microbiological characteristics of infection are the bacterial adhesion on the native joint or prosthetic material, the bacterial biofilm formation, the development of small colony variants (SCV) as sessile bacterial types and the increasing resistance to antibiotics. PMID:19834588

  2. Differences in pathogenicity, response to vaccination, and innate immune responses in different types of ducks infected with a virulent H5N1 highly pathogenic avian influenza virus from Vietnam

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Wild ducks are reservoirs of avian influenza viruses in nature, and usually don’t show signs of disease. However, some Asian lineage H5N1 highly pathogenic avian influenza (HPAI) viruses can cause disease and death in both wild and domestic ducks. The objective of this study was to compare the cli...

  3. 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

  4. Pathogenicity of H5N1 HPAI viruses from Vietnam in chickens and ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ducks and other wild aquatic birds are the natural reservoir of influenza type A viruses, and influenza viruses in these species normally is an asymptomatic infection. Even the viruses that are highly pathogenic for chickens typically can infect but do not cause disease in domestic ducks. However,...

  5. 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

  6. 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.

  7. Attenuation of pathogenic immune responses during infection with human and simian immunodeficiency virus (HIV/SIV) by the tetracycline derivative minocycline.

    PubMed

    Drewes, Julia L; Szeto, Gregory L; Engle, Elizabeth L; Liao, Zhaohao; Shearer, Gene M; Zink, M Christine; Graham, David R

    2014-01-01

    HIV immune pathogenesis is postulated to involve two major mechanisms: 1) chronic innate immune responses that drive T cell activation and apoptosis and 2) induction of immune regulators that suppress T cell function and proliferation. Both arms are elevated chronically in lymphoid tissues of non-natural hosts, which ultimately develop AIDS. However, these mechanisms are not elevated chronically in natural hosts of SIV infection that avert immune pathogenesis despite similarly high viral loads. In this study we investigated whether minocycline could modulate these pathogenic antiviral responses in non-natural hosts of HIV and SIV. We found that minocycline attenuated in vitro induction of type I interferon (IFN) and the IFN-stimulated genes indoleamine 2,3-dioxygenase (IDO1) and TNF-related apoptosis inducing ligand (TRAIL) in human plasmacytoid dendritic cells and PBMCs exposed to aldrithiol-2 inactivated HIV or infectious influenza virus. Activation-induced TRAIL and expression of cytotoxic T-lymphocyte antigen 4 (CTLA-4) in isolated CD4+ T cells were also reduced by minocycline. Translation of these in vitro findings to in vivo effects, however, were mixed as minocycline significantly reduced markers of activation and activation-induced cell death (CD25, Fas, caspase-3) but did not affect expression of IFNβ or the IFN-stimulated genes IDO1, FasL, or Mx in the spleens of chronically SIV-infected pigtailed macaques. TRAIL expression, reflecting the mixed effects of minocycline on activation and type I IFN stimuli, was reduced by half, but this change was not significant. These results show that minocycline administered after infection may protect against aspects of activation-induced cell death during HIV/SIV immune disease, but that in vitro effects of minocycline on type I IFN responses are not recapitulated in a rapid progressor model in vivo.

  8. Viruses, Other Pathogenic Microorganisms and Esophageal Cancer

    PubMed Central

    Xu, Wenjia; Liu, Zhongshun; Bao, Qunchao; Qian, Zhikang

    2015-01-01

    Background Esophageal cancer (EC) is the eighth most prevalent malignant tumor and the sixth leading cause of cancer mortality throughout the world. Despite the technical developments in diagnosis and treatment, the 5-year survival rate is still low. The etiology of EC remains poorly understood; multiple risk factors may be involved and account for the great variation in EC incidence in different geographic regions. Summary Infection with carcinogenetic pathogens has been proposed as a risk factor for EC. This review explores the recent studies on the association of human papillomavirus (HPV), Epstein-Barr virus (EBV), Helicobacter pylori and esophageal bacterial biota with EC. Key Message Among the above-mentioned pathogens, HPV most likely contributes to esophageal squamous cell carcinoma (ESCC) in high-risk populations. New techniques are being applied to studies on the role of infection in EC, which will inevitably bring novel ideas to the field in the near future. Practical Implications Multiple meta-analyses support the finding of a higher HPV detection rate in regions associated with high risk for ESCC compared to low-risk areas. A potential role of HPV in the rise of esophageal adenocarcinoma (EAC) was proposed recently. However, further studies are required before a firm conclusion can be drawn. Less work has been done in studying the association between EBV and ESCC, and the results are quite controversial. H. pylori infection is found to be inversely related to EC, which is probably due to the reduced incidence of gastroesophageal reflux disease. Analysis of the esophageal bacterial biota revealed distinct clusters of bacteria in normal and diseased esophagi. A type II microbiome rich in Gram-negative bacteria potentially contributes to EAC by inducing chronic inflammation. Novel findings from such studies as these may benefit public health by justifying anti-infection measures to prevent EC. PMID:26674173

  9. [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.

  10. New evidence that deformed wing virus and black queen cell virus are multi-host pathogens.

    PubMed

    Zhang, X; He, S Y; Evans, J D; Pettis, J S; Yin, G F; Chen, Y P

    2012-01-01

    The host-range breadth of pathogens can have important consequences for pathogens' long term evolution and virulence, and play critical roles in the emergence and spread of the new diseases. Black queen cell virus (BQCV) and Deformed wing virus (DWV) are the two most common and prevalent viruses in European honey bees, Apis mellifera. Here we provide the evidence that BQCV and DWV infect wild species of honey bees, Apis florea and Apis dorsata. Phylogenetic analyses suggest that these viruses might have moved from A. mellifera to wild bee species and that genetic relatedness as well as the geographical proximity of host species likely play an important role in host range of the viruses. The information obtained from this present study can have important implication for understanding the population structure of bee virus as well as host-virus interactions.

  11. Microarray analysis following infection with highly pathogenic avian influenza H5N1 virus in naive and vaccinated SPF chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza (AI) is a viral disease of poultry that remains a constant threat to commercial poultry throughout the world. Within the last few years, outbreaks of highly pathogenic avian influenza (HPAI) H5N1 have originated in Southeast Asia and spread to several European, Middle Eastern, and A...

  12. Early responses of chicken lungs and spleens to infection with highly pathogenic avian influenza virus using microarray analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Within the last few years, outbreaks of highly pathogenic avian influenza (HPAI) have originated in Asia and spread through several Middle Eastern, African and European countries, resulting in one of the most serious animal disease incident in recent history. These outbreaks were characterized by t...

  13. Molecular Basis of Latency in Pathogenic Human Viruses

    NASA Astrophysics Data System (ADS)

    Garcia-Blanco, Mariano A.; Cullen, Bryan R.

    1991-11-01

    Several human viruses are able to latently infect specific target cell populations in vivo. Analysis of the replication cycles of herpes simplex virus, Epstein-Barr virus, and human immunodeficiency virus suggests that the latent infections established by these human pathogens primarily result from a lack of host factors critical for the expression of viral early gene products. The subsequent activation of specific cellular transcription factors in response to extracellular stimuli can induce the expression of these viral regulatory proteins and lead to a burst of lytic viral replication. Latency in these eukaryotic viruses therefore contrasts with latency in bacteriophage, which is maintained primarily by the expression of virally encoded repressors of lytic replication.

  14. Low-Pathogenic Avian Influenza Viruses in Wild House Mice

    PubMed Central

    Shriner, Susan A.; VanDalen, Kaci K.; Mooers, Nicole L.; Ellis, Jeremy W.; Sullivan, Heather J.; Root, J. Jeffrey; Pelzel, Angela M.; Franklin, Alan B.

    2012-01-01

    Background Avian influenza viruses are known to productively infect a number of mammal species, several of which are commonly found on or near poultry and gamebird farms. While control of rodent species is often used to limit avian influenza virus transmission within and among outbreak sites, few studies have investigated the potential role of these species in outbreak dynamics. Methodology/Principal Findings We trapped and sampled synanthropic mammals on a gamebird farm in Idaho, USA that had recently experienced a low pathogenic avian influenza outbreak. Six of six house mice (Mus musculus) caught on the outbreak farm were presumptively positive for antibodies to type A influenza. Consequently, we experimentally infected groups of naïve wild-caught house mice with five different low pathogenic avian influenza viruses that included three viruses derived from wild birds and two viruses derived from chickens. Virus replication was efficient in house mice inoculated with viruses derived from wild birds and more moderate for chicken-derived viruses. Mean titers (EID50 equivalents/mL) across all lung samples from seven days of sampling (three mice/day) ranged from 103.89 (H3N6) to 105.06 (H4N6) for the wild bird viruses and 102.08 (H6N2) to 102.85 (H4N8) for the chicken-derived viruses. Interestingly, multiple regression models indicated differential replication between sexes, with significantly (p<0.05) higher concentrations of avian influenza RNA found in females compared with males. Conclusions/Significance Avian influenza viruses replicated efficiently in wild-caught house mice without adaptation, indicating mice may be a risk pathway for movement of avian influenza viruses on poultry and gamebird farms. Differential virus replication between males and females warrants further investigation to determine the generality of this result in avian influenza disease dynamics. PMID:22720076

  15. Pathogenicity and Transmission of H5 and H7 Highly Pathogenic Avian Influenza Viruses in Mallards.

    PubMed

    Pantin-Jackwood, Mary J; Costa-Hurtado, Mar; Shepherd, Eric; DeJesus, Eric; Smith, Diane; Spackman, Erica; Kapczynski, Darrell R; Suarez, David L; Stallknecht, David E; Swayne, David E

    2016-11-01

    Wild aquatic birds have been associated with the intercontinental spread of H5 subtype highly pathogenic avian influenza (HPAI) viruses of the A/goose/Guangdong/1/96 (Gs/GD) lineage during 2005, 2010, and 2014, but dispersion by wild waterfowl has not been implicated with spread of other HPAI viruses. To better understand why Gs/GD H5 HPAI viruses infect and transmit more efficiently in waterfowl than other HPAI viruses, groups of mallard ducks were challenged with one of 14 different H5 and H7 HPAI viruses, including a Gs/GD lineage H5N1 (clade 2.2) virus from Mongolia, part of the 2005 dispersion, and the H5N8 and H5N2 index HPAI viruses (clade 2.3.4.4) from the United States, part of the 2014 dispersion. All virus-inoculated ducks and contact exposed ducks became infected and shed moderate to high titers of the viruses, with the exception that mallards were resistant to Ck/Pennsylvania/83 and Ck/Queretaro/95 H5N2 HPAI virus infection. Clinical signs were only observed in ducks challenged with the H5N1 2005 virus, which all died, and with the H5N8 and H5N2 2014 viruses, which had decreased weight gain and fever. These three viruses were also shed in higher titers by the ducks, which could facilitate virus transmission and spread. This study highlights the possible role of wild waterfowl in the spread of HPAI viruses.

  16. A computationally optimized broadly reactive H5 hemagglutinin vaccine provides protection against homologous and heterologous H5N1 highly pathogenic avian influenza virus infection in chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since its emergence in 1996 in China, H5N1 highly pathogenic avian influenza (HPAI) virus has continuously evolved into different genetic clades that have created challenges to maintaining antigenically relevant H5N1 vaccine seeds. Therefore, a universal (multi-hemagglutinin [HA] subtype) or more c...

  17. Detection of pathogenic viruses in sewage provided early warnings of hepatitis A virus and norovirus outbreaks.

    PubMed

    Hellmér, Maria; Paxéus, Nicklas; Magnius, Lars; Enache, Lucica; Arnholm, Birgitta; Johansson, Annette; Bergström, Tomas; Norder, Heléne

    2014-11-01

    Most persons infected with enterically transmitted viruses shed large amounts of virus in feces for days or weeks, both before and after onset of symptoms. Therefore, viruses causing gastroenteritis may be detected in wastewater, even if only a few persons are infected. In this study, the presence of eight pathogenic viruses (norovirus, astrovirus, rotavirus, adenovirus, Aichi virus, parechovirus, hepatitis A virus [HAV], and hepatitis E virus) was investigated in sewage to explore whether their identification could be used as an early warning of outbreaks. Samples of the untreated sewage were collected in proportion to flow at Ryaverket, Gothenburg, Sweden. Daily samples collected during every second week between January and May 2013 were pooled and analyzed for detection of viruses by concentration through adsorption to milk proteins and PCR. The largest amount of noroviruses was detected in sewage 2 to 3 weeks before most patients were diagnosed with this infection in Gothenburg. The other viruses were detected at lower levels. HAV was detected between weeks 5 and 13, and partial sequencing of the structural VP1protein identified three different strains. Two strains were involved in an ongoing outbreak in Scandinavia and were also identified in samples from patients with acute hepatitis A in Gothenburg during spring of 2013. The third strain was unique and was not detected in any patient sample. The method used may thus be a tool to detect incipient outbreaks of these viruses and provide early warning before the causative pathogens have been recognized in health care.

  18. A study on pathogens of Chinese prawn ( Penaeus Chinensis) virus diseases

    NASA Astrophysics Data System (ADS)

    Sun, Xiu-Qin; Zhang, Jin-Xing

    1995-09-01

    This pathogenic study shows that the viral diseases of Chinese prawns ( Penaeus chinensis, O'sbeck) is due to three kinds of viruses: epithelium envelope baculovirus of Penaeus chinensis (EEBV-PC, detected by the authors in 1993), infections hypodermal and hematopoietic necrosis virus, and hepatopancreatic parvo-like virus, and that the first two viruses seem to be the main pathogens of the epidemic in the northern regions in 1993.

  19. Effect of statin treatments on highly pathogenic avian influenza H5N1, seasonal and H1N1pdm09 virus infections in BALB/c mice

    PubMed Central

    Kumaki, Yohichi; Morrey, John D; Barnard, Dale L

    2013-01-01

    Statins are used to control elevated cholesterol or hypercholesterolemia, but have previously been reported to have antiviral properties. Aims To show efficacy of statins in various influenza virus mouse models. Materials & methods BALB/c mice were treated intraperitoneally or orally with several types of statins (simvastatin, lovastatin, mevastatin, pitavastatin, atorvastatin or rosuvastatin) at various concentrations before or after infection with either influenza A/Duck/ MN/1525/81 H5N1 virus, influenza A/Vietnam/1203/2004 H5N1 virus, influenza A/ Victoria/3/75 H3N2 virus, influenza A/NWS/33 H1N1 virus or influenza A/CA/04/09 H1N1pdm09 virus. Results The statins administered intraperitoneally or orally at any dose did not significantly enhance the total survivors relative to untreated controls. In addition, infected mice receiving any concentration of statin were not protected against weight loss due to the infection. None of the statins significantly increased the mean day of death relative to mice in the placebo treatment group. Furthermore, the statins had relatively few ameliorative effects on lung pathology or lung weights at day 3 and 6 after virus exposure, although mice treated with simvastatin did have improved lung function as measured by arterial saturated oxygen levels in one experiment. Conclusion Statins showed relatively little efficacy in any mouse model used by any parameter tested. PMID:23420457

  20. 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.

  1. Protection against H5N1 highly pathogenic avian and pandemic (H1N1) 2009 influenza virus infection in cynomolgus monkeys by an inactivated H5N1 whole particle vaccine.

    PubMed

    Nakayama, Misako; Shichinohe, Shintaro; Itoh, Yasushi; Ishigaki, Hirohito; Kitano, Mitsutaka; Arikata, Masahiko; Pham, Van Loi; Ishida, Hideaki; Kitagawa, Naoko; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Ichikawa, Takaya; Tsuchiya, Hideaki; Nakamura, Shinichiro; Le, Quynh Mai; Ito, Mutsumi; Kawaoka, Yoshihiro; Kida, Hiroshi; Ogasawara, Kazumasa

    2013-01-01

    H5N1 highly pathogenic avian influenza virus (HPAIV) infection has been reported in poultry and humans with expanding clade designations. Therefore, a vaccine that induces immunity against a broad spectrum of H5N1 viruses is preferable for pandemic preparedness. We established a second H5N1 vaccine candidate, A/duck/Hokkaido/Vac-3/2007 (Vac-3), in our virus library and examined the efficacy of inactivated whole particles of this strain against two clades of H5N1 HPAIV strains that caused severe morbidity in cynomolgus macaques. Virus propagation in vaccinated macaques infected with either of the H5N1 HPAIV strains was prevented compared with that in unvaccinated macaques. This vaccine also prevented propagation of a pandemic (H1N1) 2009 virus in macaques. In the vaccinated macaques, neutralization activity, which was mainly shown by anti-hemagglutinin antibody, against H5N1 HPAIVs in plasma was detected, but that against H1N1 virus was not detected. However, neuraminidase inhibition activity in plasma and T-lymphocyte responses in lymph nodes against H1N1 virus were detected. Therefore, cross-clade and heterosubtypic protective immunity in macaques consisted of humoral and cellular immunity induced by vaccination with Vac-3.

  2. Giant viruses of amoebae as potential human pathogens.

    PubMed

    Colson, Philippe; La Scola, Bernard; Raoult, Didier

    2013-01-01

    Giant viruses infecting phagocytic protists are composed of mimiviruses, the record holders of particle and genome size amongst viruses, and marseilleviruses. Since the discovery in 2003 at our laboratory of the first of these giant viruses, the Mimivirus, a growing body of data has revealed that they are common inhabitants of our biosphere. Moreover, from the outset, the story of Mimivirus has been linked to that of patients exhibiting pneumonia and it was shown that patients developed antibodies to this amoebal pathogen. Since then, there have been several proven cases of human infection or colonization with giant viruses of amoebae, which are known to host several bacteria that are human pathogens. Mimiviruses and marseilleviruses represent a major challenge in human pathology, as virological procedures implemented to date have not used appropriate media to allow their culture, and molecular techniques have used filtration steps that likely prevented their detection. Nevertheless, there is an increasing body of evidence that mimiviruses might cause pneumonia and that humans carry marseilleviruses, and re-analyses of metagenomic databases have provided evidence that these giant viruses can be common in human samples. The proportion of human infections related to these giant mimiviruses and marseilleviruses and the precise short- and long-term consequences of these infections have been scarcely investigated so far and should be the subject of future works.

  3. [Transmissibility and pathogenicity of influenza viruses].

    PubMed

    Horimoto, Taisuke; Yamada, Shinya; Kawaoka, Yoshihiro

    2010-09-01

    In the spring of 2009, a novel swine-origin H1N1 virus, whose antigenicity is quite different from those of seasonal human H1N1 strains, emerged in Mexico and readily transmitted and spread among humans, resulting in the first influenza pandemic in the 21st century. Molecular analyses of the pandemic H1N1 2009 viruses indicate low-pathogenic features for humans, although worldwide transmission of the virus and a considerable numbers of lethal cases with acute pneumonia have been observed in the first wave of the current pandemic. Here, we review our current molecular knowledge of transmissibility and pathogenicity of influenza viruses and discuss the future aspects of the pandemic virus.

  4. Integrated omics analysis of pathogenic host responses during pandemic H1N1 influenza virus infection: the crucial role of lipid metabolism

    PubMed Central

    Tisoncik-Go, Jennifer; Gasper, David J.; Kyle, Jennifer E.; Eisfeld, Amie J.; Selinger, Christian; Hatta, Masato; Morrison, Juliet; Korth, Marcus J.; Zink, Erika M.; Kim, Young-Mo; Schepmoes, Athena A.; Nicora, Carrie D.; Purvine, Samuel O.; Weitz, Karl K.; Peng, Xinxia; Green, Richard R.; Tilton, Susan C.; Webb-Robertson, Bobbie-Jo; Waters, Katrina M.; Metz, Thomas O.; Smith, Richard D.; Kawaoka, Yoshihiro; Suresh, M.; Josset, Laurence; Katze, Michael G.

    2016-01-01

    SUMMARY Pandemic influenza viruses modulate pro-inflammatory responses that can lead to immunopathogenesis. We present an extensive and systematic profiling of lipids, metabolites and proteins in respiratory compartments of ferrets infected with either 1918 or 2009 human pandemic H1N1 influenza viruses. Integrative analysis of high-throughput omics data with virologic and histopathologic data uncovered relationships between host responses and phenotypic outcomes of viral infection. Pro-inflammatory lipid precursors in the trachea following 1918 infection correlated with severe tracheal lesions. Using an algorithm to infer cell quantity changes from gene expression data, we found enrichment of distinct T cell subpopulations in the trachea. There was also a predicted increase in inflammatory monocytes in the lung of 1918 virus-infected animals that was sustained throughout infection. This study presents a unique resource to the influenza research community and demonstrates the utility of an integrative systems approach for characterization of lipid metabolism alterations underlying respiratory responses to viruses. PMID:26867183

  5. 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...

  6. Drosophila as a genetic model for studying pathogenic human viruses.

    PubMed

    Hughes, Tamara T; Allen, Amanda L; Bardin, Joseph E; Christian, Megan N; Daimon, Kansei; Dozier, Kelsey D; Hansen, Caom L; Holcomb, Lisa M; Ahlander, Joseph

    2012-02-05

    Viruses are infectious particles whose viability is dependent on the cells of living organisms, such as bacteria, plants, and animals. It is of great interest to discover how viruses function inside host cells in order to develop therapies to treat virally infected organisms. The fruit fly Drosophila melanogaster is an excellent model system for studying the molecular mechanisms of replication, amplification, and cellular consequences of human viruses. In this review, we describe the advantages of using Drosophila as a model system to study human viruses, and highlight how Drosophila has been used to provide unique insight into the gene function of several pathogenic viruses. We also propose possible directions for future research in this area.

  7. Drosophila as a genetic model for studying pathogenic human viruses

    PubMed Central

    Hughes, Tamara T.; Allen, Amanda L.; Bardin, Joseph E.; Christian, Megan N.; Daimon, Kansei; Dozier, Kelsey D.; Hansen, Caom L.; Holcomb, Lisa M.; Ahlander, Joseph

    2011-01-01

    Viruses are infectious particles whose viability is dependent on the cells of living organisms, such as bacteria, plants, and animals. It is of great interest to discover how viruses function inside host cells in order to develop therapies to treat virally infected organisms. The fruit fly Drosophila melanogaster is an excellent model system for studying the molecular mechanisms of replication, amplification, and cellular consequences of human viruses. In this review, we describe the advantages of using Drosophila as a model system to study human viruses, and highlight how Drosophila has been used to provide unique insight into the gene function of several pathogenic viruses. We also propose possible directions for future research in this area. PMID:22177780

  8. Association of Mx1 Asn631 variant alleles with reductions in morbidity, early mortality, viral shedding, and cytokine responses in chickens infected with a highly pathogenic avian influenza virus.

    PubMed

    Ewald, Sandra J; Kapczynski, Darrell R; Livant, Emily J; Suarez, David L; Ralph, John; McLeod, Scott; Miller, Carolyn

    2011-06-01

    Myxovirus-resistance (Mx) proteins are produced by host cells in response to type I interferons, and some members of the Mx gene family in mammals have been shown to limit replication of influenza and other viruses. According to an early report, chicken Mx1 variants encoding Asn at position 631 have antiviral activity, whereas variants with Ser at 631 lack activity in experiments evaluating Mx1 complementary DNA (cDNA) expressed ectopically in a cell line. We evaluated whether the Mx1 631 dimorphism influenced pathogenesis of highly pathogenic avian influenza virus (HPAIV) infection in chickens of two commercial broiler lines, each segregating for Asn631 and Ser631 variants. Following intranasal infection with HPAIV strain A/Chicken/Queretaro/14588-19/1995 H5N2, chickens homozygous for Asn631 allele were significantly more resistant to disease based on early mortality, morbidity, or virus shedding than Ser631 homozygotes. Higher amounts of splenic cytokine transcripts were observed in the Ser631 birds after infection, consistent with higher viral loads seen in this group and perhaps contributing to their higher morbidity. Nucleotide sequence determination of Mx1 cDNAs demonstrated that the Asn631 variants in the two chicken lines differed at several amino acid positions outside 631. In vitro experiments with a different influenza strain (low pathogenicity) failed to demonstrate an effect of Mx1 Asn631 on viral replication suggesting that in vivo responses may differ markedly from in vitro, or that choice of virus strain may be critical in demonstrating effects of chicken Mx1. Overall, these studies provide the first evidence that Mx1 has antiviral effects in chickens infected with influenza virus.

  9. 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 ...

  10. Novel Eurasian highly pathogenic avian influenza A H5 viruses in wild birds, Washington, USA, 2014.

    PubMed

    Ip, Hon S; Torchetti, Mia Kim; Crespo, Rocio; Kohrs, Paul; DeBruyn, Paul; Mansfield, Kristin G; Baszler, Timothy; Badcoe, Lyndon; Bodenstein, Barbara; Shearn-Bochsler, Valerie; Killian, Mary Lea; Pedersen, Janice C; Hines, Nichole; Gidlewski, Thomas; DeLiberto, Thomas; Sleeman, Jonathan M

    2015-05-01

    Novel Eurasian lineage avian influenza A(H5N8) virus has spread rapidly and globally since January 2014. In December 2014, H5N8 and reassortant H5N2 viruses were detected in wild birds in Washington, USA, and subsequently in backyard birds. When they infect commercial poultry, these highly pathogenic viruses pose substantial trade issues.

  11. Novel Eurasian highly pathogenic influenza A H5 viruses in wild birds, Washington, USA

    USGS Publications Warehouse

    Ip, Hon S.; Kim Torchetti, Mia; Crespo, Rocio; Kohrs, Paul; DeBruyn, Paul; Mansfield, Kristin G.; Baszler, Timothy; Badcoe, Lyndon; Bodenstein, Barbara L.; Shearn-Bochsler, Valerie I.; Killian, Mary Lea; Pederson, Janice C.; Hines, Nichole; Gidlewski, Thomas; DeLiberto, Thomas; Sleeman, Jonathan M.

    2015-01-01

    Novel Eurasian lineage avian influenza A(H5N8) virus has spread rapidly and globally since January 2014. In December 2014, H5N8 and reassortant H5N2 viruses were detected in wild birds in Washington, USA, and subsequently in backyard birds. When they infect commercial poultry, these highly pathogenic viruses pose substantial trade issues.

  12. Susceptibility of swine to H5 and H7 low pathogenic avian influenza viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The ability of pigs to become infected with low pathogenic avian influenza (LPAI) viruses from an avian reservoir, and then generate mammalian adaptable influenza A viruses (IAVs) is difficult to determine. Yet, it is an important link to understanding any relationship between LPAI virus ecology and...

  13. 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.

  14. 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

  15. Comparison of the pathogenicity of different H5N1 HPAI viruses in chickens and ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Contrary to what is observed in chickens where infection with highly pathogenic avian influenza (HPAI) viruses produce fatal disease, the Asian H5N1 HPAI viruses have changed from producing mild respiratory infections in ducks to some strains causing systemic disease and death. In order to further ...

  16. Hepatitis E virus as an emerging zoonotic pathogen.

    PubMed

    Park, Woo-Jung; Park, Byung-Joo; Ahn, Hee-Seop; Lee, Joong-Bok; Park, Seung-Yong; Song, Chang-Seon; Lee, Sang-Won; Yoo, Han-Sang; Choi, In-Soo

    2016-03-01

    Hepatitis E outbreaks are a serious public health concern in developing countries. The disease causes acute infections, primarily in young adults. The mortality rate is approximately 2%; however, it can exceed 20% in pregnant women in some regions in India. The causative agent, hepatitis E virus (HEV), has been isolated from several animal species, including pigs. HEV genotypes 3 and 4 have been isolated from both humans and animals, and are recognized as zoonotic pathogens. Seroprevalence studies in animals and humans indirectly suggest that HEV infections occur worldwide. The virus is primarily transmitted to humans via undercooked animal meats in developed countries. Moreover, transfusion- and transplantation-mediated HEV infections have recently been reported. This review summarizes the general characteristics of hepatitis E, HEV infection status in animals and humans, the zoonotic transmission modes of HEV, and HEV vaccine development status.

  17. Hepatitis E virus as an emerging zoonotic pathogen

    PubMed Central

    Park, Woo-Jung; Park, Byung-Joo; Ahn, Hee-Seop; Lee, Joong-Bok; Park, Seung-Yong; Song, Chang-Seon; Lee, Sang-Won; Yoo, Han-Sang

    2016-01-01

    Hepatitis E outbreaks are a serious public health concern in developing countries. The disease causes acute infections, primarily in young adults. The mortality rate is approximately 2%; however, it can exceed 20% in pregnant women in some regions in India. The causative agent, hepatitis E virus (HEV), has been isolated from several animal species, including pigs. HEV genotypes 3 and 4 have been isolated from both humans and animals, and are recognized as zoonotic pathogens. Seroprevalence studies in animals and humans indirectly suggest that HEV infections occur worldwide. The virus is primarily transmitted to humans via undercooked animal meats in developed countries. Moreover, transfusion- and transplantation-mediated HEV infections have recently been reported. This review summarizes the general characteristics of hepatitis E, HEV infection status in animals and humans, the zoonotic transmission modes of HEV, and HEV vaccine development status. PMID:27051334

  18. 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.

  19. Laser inactivation of pathogenic viruses in water

    NASA Astrophysics Data System (ADS)

    Grishkanich, Alexander; Zhevlakov, Alexander; Kascheev, Sergey; Sidorov, Igor; Ruzankina, Julia; Yakovlev, Alexey; Mak, Andrey

    2016-03-01

    Currently there is a situation that makes it difficult to provide the population with quality drinking water for the sanitary-hygienic requirements. One of the urgent problems is the need for water disinfection. Since the emergence of microorganisms that are pathogens transmitted through water such as typhoid, cholera, etc. requires constant cleansing of waters against pathogenic bacteria. In the water treatment process is destroyed up to 98% of germs, but among the remaining can be pathogenic viruses, the destruction of which requires special handling. As a result, the conducted research the following methods have been proposed for combating harmful microorganisms: sterilization of water by laser radiation and using a UV lamp.

  20. Highly pathogenic Avian Influenza A(H5N1) virus infection among workers at live bird markets, Bangladesh, 2009-2010.

    PubMed

    Nasreen, Sharifa; Khan, Salah Uddin; Luby, Stephen P; Gurley, Emily S; Abedin, Jaynal; Zaman, Rashid Uz; Sohel, Badrul Munir; Rahman, Mustafizur; Hancock, Kathy; Levine, Min Z; Veguilla, Vic; Wang, David; Holiday, Crystal; Gillis, Eric; Sturm-Ramirez, Katharine; Bresee, Joseph S; Rahman, Mahmudur; Uyeki, Timothy M; Katz, Jacqueline M; Azziz-Baumgartner, Eduardo

    2015-04-01

    The risk for influenza A(H5N1) virus infection is unclear among poultry workers in countries where the virus is endemic. To assess H5N1 seroprevalence and seroconversion among workers at live bird markets (LBMs) in Bangladesh, we followed a cohort of workers from 12 LBMs with existing avian influenza surveillance. Serum samples from workers were tested for H5N1 antibodies at the end of the study or when LBM samples first had H5N1 virus-positive test results. Of 404 workers, 9 (2%) were seropositive at baseline. Of 284 workers who completed the study and were seronegative at baseline, 6 (2%) seroconverted (7 cases/100 poultry worker-years). Workers who frequently fed poultry, cleaned feces from pens, cleaned food/water containers, and did not wash hands after touching sick poultry had a 7.6 times higher risk for infection compared with workers who infrequently performed these behaviors. Despite frequent exposure to H5N1 virus, LBM workers showed evidence of only sporadic infection.

  1. The role of carbohydrates in infection strategies of enteric pathogens.

    PubMed

    Kato, Kentaro; Ishiwa, Akiko

    2015-03-01

    Enteric pathogens cause considerable public health concerns worldwide including tropical regions. Here, we review the roles of carbohydrates in the infection strategies of various enteric pathogens including viruses, bacteria and protozoa, which infect the epithelial lining of the human and animal intestine. At host cell entry, enteric viruses, including norovirus, recognize mainly histo-blood group antigens. At the initial step of bacterial infections, carbohydrates also function as receptors for attachment. Here, we describe the function of carbohydrates in infection by Salmonella enterica and several bacterial species that produce a variety of fimbrial adhesions. During invasion by enteropathogenic protozoa, apicomplexan parasites utilize sialic acids or sulfated glycans. Carbohydrates serve as receptors for infection by these microbes; however, their usage of carbohydrates varies depending on the microbe. On the surface of the mucosal tissues of the gastrointestinal tract, various carbohydrate moieties are present and play a crucial role in infection, representing the site of infection or route of access for most microbes. During the infection and/or invasion process of the microbes, carbohydrates function as receptors for various microbes, but they can also function as a barrier to infection. One approach to develop effective prophylactic and therapeutic antimicrobial agents is to modify the drug structure. Another approach is to modify the mode of inhibition of infection depending on the individual pathogen by using and mimicking the interactions with carbohydrates. In addition, similarities in mode of infection may also be utilized. Our findings will be useful in the development of new drugs for the treatment of enteric pathogens.

  2. Multiple infections of rodents with zoonotic pathogens in Austria.

    PubMed

    Schmidt, Sabrina; Essbauer, Sandra S; Mayer-Scholl, Anne; Poppert, Sven; Schmidt-Chanasit, Jonas; Klempa, Boris; Henning, Klaus; Schares, Gereon; Groschup, Martin H; Spitzenberger, Friederike; Richter, Dania; Heckel, Gerald; Ulrich, Rainer G

    2014-07-01

    Rodents are important reservoirs for a large number of zoonotic pathogens. We examined the occurrence of 11 viral, bacterial, and parasitic agents in rodent populations in Austria, including three different hantaviruses, lymphocytic choriomeningitis virus, orthopox virus, Leptospira spp., Borrelia spp., Rickettsia spp., Bartonella spp., Coxiella burnetii, and Toxoplasma gondii. In 2008, 110 rodents of four species (40 Clethrionomys glareolus, 29 Apodemus flavicollis, 26 Apodemus sylvaticus, and 15 Microtus arvalis) were trapped at two rural sites in Lower Austria. Chest cavity fluid and samples of lung, spleen, kidney, liver, brain, and ear pinna skin were collected. We screened selected tissue samples for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, Leptospira, Borrelia, Rickettsia, Bartonella spp., C. burnetii, and T. gondii by RT-PCR/PCR and detected nucleic acids of Tula hantavirus, Leptospira spp., Borrelia afzelii, Rickettsia spp., and different Bartonella species. Serological investigations were performed for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, and Rickettsia spp. Here, Dobrava-Belgrade hantavirus-, Tula hantavirus-, lymphocytic choriomeningitis virus-, orthopox virus-, and rickettsia-specific antibodies were demonstrated. Puumala hantavirus, C. burnetii, and T. gondii were neither detected by RT-PCR/PCR nor by serological methods. In addition, multiple infections with up to three pathogens were shown in nine animals of three rodent species from different trapping sites. In conclusion, these results show that rodents in Austria may host multiple zoonotic pathogens. Our observation raises important questions regarding the interactions of different pathogens in the host, the countermeasures of the host's immune system, the impact of the host-pathogen interaction on the fitness of the host, and the spread of infectious agents among wild rodents and from those to other animals or humans.

  3. Multiple Infections of Rodents with Zoonotic Pathogens in Austria

    PubMed Central

    Schmidt, Sabrina; Essbauer, Sandra S.; Mayer-Scholl, Anne; Poppert, Sven; Schmidt-Chanasit, Jonas; Klempa, Boris; Henning, Klaus; Schares, Gereon; Groschup, Martin H.; Spitzenberger, Friederike; Richter, Dania; Heckel, Gerald

    2014-01-01

    Abstract Rodents are important reservoirs for a large number of zoonotic pathogens. We examined the occurrence of 11 viral, bacterial, and parasitic agents in rodent populations in Austria, including three different hantaviruses, lymphocytic choriomeningitis virus, orthopox virus, Leptospira spp., Borrelia spp., Rickettsia spp., Bartonella spp., Coxiella burnetii, and Toxoplasma gondii. In 2008, 110 rodents of four species (40 Clethrionomys glareolus, 29 Apodemus flavicollis, 26 Apodemus sylvaticus, and 15 Microtus arvalis) were trapped at two rural sites in Lower Austria. Chest cavity fluid and samples of lung, spleen, kidney, liver, brain, and ear pinna skin were collected. We screened selected tissue samples for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, Leptospira, Borrelia, Rickettsia, Bartonella spp., C. burnetii, and T. gondii by RT-PCR/PCR and detected nucleic acids of Tula hantavirus, Leptospira spp., Borrelia afzelii, Rickettsia spp., and different Bartonella species. Serological investigations were performed for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, and Rickettsia spp. Here, Dobrava-Belgrade hantavirus-, Tula hantavirus-, lymphocytic choriomeningitis virus-, orthopox virus-, and rickettsia-specific antibodies were demonstrated. Puumala hantavirus, C. burnetii, and T. gondii were neither detected by RT-PCR/PCR nor by serological methods. In addition, multiple infections with up to three pathogens were shown in nine animals of three rodent species from different trapping sites. In conclusion, these results show that rodents in Austria may host multiple zoonotic pathogens. Our observation raises important questions regarding the interactions of different pathogens in the host, the countermeasures of the host's immune system, the impact of the host–pathogen interaction on the fitness of the host, and the spread of infectious agents among wild rodents and from those to other animals or humans. PMID

  4. The effect of NS1 gene exchange on the pathogenicity of H5N1 HPAI viruses in ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Until 2002, H5N1 highly pathogenic avian influenza (HPAI) viruses caused only mild respiratory infections in ducks. Since then, new viruses have emerged that cause systemic disease and high mortality in ducks and other waterfowl. Studies on HPAI virus pathogenicity in ducks have been limited and t...

  5. The role of NS protein in the pathogenicity of HPAI H5N1 viruses in ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Until 2002, highly pathogenic avian influenza (HPAI) H5N1 viruses caused no disease or only mild respiratory infections in ducks. Since then, new viruses have emerged that cause systemic disease and high mortality in ducks and other waterfowl. Studies on HPAI virus pathogenicity in ducks have been...

  6. Replication and pathogenesis associated with H5N1, H5N2, and H5N3 low-pathogenic avian influenza virus infection in chickens and ducks.

    PubMed

    Mundt, Egbert; Gay, Lauren; Jones, Les; Saavedra, Geraldine; Tompkins, S Mark; Tripp, Ralph A

    2009-01-01

    A comparative study examining replication and disease pathogenesis associated with low-pathogenic H5N1, H5N2, or H5N3 avian influenza virus (AIV) infection of chickens and ducks was performed. The replication and pathogenesis of highly pathogenic AIV (HPAIV) has received substantial attention; however, the behavior of low-pathogenic AIVs, which serve as precursors to HPAIVs, has received less attention. Thus, chickens or ducks were inoculated with an isolate from a wild bird [A/Mute Swan/MI/451072/06 (H5N1)] or isolates from chickens [A/Ck/PA/13609/93 (H5N2), A/Ck/TX/167280-4/02 (H5N3)], and virus replication, induction of a serological response, and disease pathogenesis were investigated, and the hemagglutinin and neuraminidase (NA) gene sequences of the isolates were determined. Virus isolated from tracheal and cloacal swabs showed that H5N1 replicated better in ducks, whereas H5N2 and H5N3 replicated better in chickens. Comparison of the NA gene sequences showed that chicken-adapted H5N2 and H5N3 isolates both have a deletion of 20 amino acids in the NA stalk region, which was absent in the H5N1 isolate. Histopathological examination of numerous organs showed that H5N2 and H5N3 isolates caused lesions in chickens in a variety of organs, but to a greater extent in the respiratory and intestinal tracts, whereas H5N1 lesions in ducks were observed mainly in the respiratory tract. This study suggests that the H5N1, H5N2, and H5N3 infections occurred at distinct sites in chicken and ducks, and that comparative studies in different model species are needed to better understand the factors influencing the evolution of these viruses.

  7. 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.

  8. 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

  9. Modeling Dental Health Care Workers' Risk of Occupational Infection from Bloodborne Pathogens.

    ERIC Educational Resources Information Center

    Capilouto, Eli; And Others

    1990-01-01

    The brief paper offers a model which permits quantification of the dental health care workers' risk of occupationally acquiring infection from bloodborne pathogens such as human immunodeficiency virus and hepatitis B virus. The model incorporates five parameters such as the probability that any individual patient is infected and number of patients…

  10. Determinants of pathogenicity of H5N1 highly pathogenic avian influenza viruses in ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ducks have been implicated in the dissemination and evolution of the H5N1 highly pathogenic avian influenza (HPAI) viruses. The pathogenicity of H5N1 HPAI viruses in domestic ducks has increased over time with some viruses producing 100% mortality in very short time. The determinants of pathogenic...

  11. 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.

  12. Differential transcription of fathead minnow immune-related genes following infection with frog virus 3, an emerging pathogen of ectothermic vertebrates.

    PubMed

    Cheng, Kwang; Escalon, B Lynn; Robert, Jacques; Chinchar, V Gregory; Garcia-Reyero, Natàlia

    2014-05-01

    Frog virus 3 (FV3) and other ranaviruses are responsible for die-offs involving wild, farmed, and captive amphibians, fish, and reptiles. To ascertain which elements of the immune system respond to infection, we explored transcriptional responses following infection of fathead minnow cells with either wild type (wt) FV3 or a knock out (KO) mutant targeting the 18 kDa immediate early gene (18K). At 8h post infection we observed marked upregulation of multiple transcripts encoding proteins affecting innate and acquired immunity. Sequences expressed 4-fold or higher in wt-infected cells included transcripts encoding interferon (IFN), IFN regulatory factors (IRFs), IFN stimulated genes (ISGs) such as Mx and MHC class I, and interleukins IL-1β, IL-8, IL-17C and IL-12. Cells infected with the 18K KO mutant (∆18K) showed qualitative differences and lower levels of induction. Collectively, these results indicate that ranavirus infection induced expression of multiple cellular genes affecting both innate and acquired immunity.

  13. 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.

  14. 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 ...

  15. 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...

  16. 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.

  17. 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

  18. Pathogenicity of molecularly cloned bovine leukemia virus.

    PubMed Central

    Rovnak, J; Boyd, A L; Casey, J W; Gonda, M A; Jensen, W A; Cockerell, G L

    1993-01-01

    To delineate the mechanisms of bovine leukemia virus (BLV) pathogenesis, four full-length BLV clones, 1, 8, 9, and 13, derived from the transformed cell line FLK-BLV and a clone construct, pBLV913, were introduced into bovine spleen cells by microinjection. Microinjected cells exhibited cytopathic effects and produced BLV p24 and gp51 antigens and infectious virus. The construct, pBLV913, was selected for infection of two sheep by inoculation of microinjected cells. After 15 months, peripheral blood mononuclear cells from these sheep served as inocula for the transfer of infection to four additional sheep. All six infected sheep seroconverted to BLV and had detectable BLV DNA in peripheral blood mononuclear cells after amplification by polymerase chain reaction. Four of the six sheep developed altered B/T-lymphocyte ratios between 33 and 53 months postinfection. One sheep died of unrelated causes, and one remained hematologically normal. Two of the affected sheep developed B lymphocytosis comparable to that observed in animals inoculated with peripheral blood mononuclear cells from BLV-infected cattle. This expanded B-lymphocyte population was characterized by elevated expression of B-cell surface markers, spontaneous blastogenesis, virus expression in vitro, and increased, polyclonally integrated provirus. One of these two sheep developed lymphocytic leukemia-lymphoma at 57 months postinfection. Leukemic cells had the same phenotype and harbored a single, monoclonally integrated provirus but produced no virus after in vitro cultivation. The range in clinical response to in vivo infection with cloned BLV suggests an important role for host immune response in the progression of virus replication and pathogenesis. Images PMID:8230433

  19. Pathogenicity of modified bat influenza virus with different M genes and its reassortment potential with swine influenza A virus.

    PubMed

    Yang, Jianmei; Lee, Jinhwa; Ma, Jingjiao; Lang, Yuekun; Nietfeld, Jerome; Li, Yuhao; Duff, Michael; Li, Yonghai; Yang, Yuju; Liu, Haixia; Zhou, Bin; Wentworth, David E; Richt, Juergen A; Li, Zejun; Ma, Wenjun

    2017-01-18

    In our previous studies the reassortant virus containing only the PR8 H1N1 matrix (M) gene in the background of the modified bat influenza Bat09:mH1mN1 virus could be generated. However, whether M genes from other origins can be rescued in the background of the Bat09:mH1mN1 virus and whether the resulting novel reassortant virus is virulent remain unknown. Herein, two reassortant viruses were generated in the background of the Bat09:mH1mN1 virus containing either a North American or a Eurasian swine influenza virus M gene. These two reassortant viruses and the reassortant virus with PR8 M as well as the control Bat09:mH1mN1 virus replicated efficiently in cultured cells, while the reassortant virus with PR8 M grew to a higher titer than the other three viruses in tested cells. Mouse studies showed that reassortant viruses with either North American or Eurasian swine influenza virus M genes did not enhance virulence, whereas the reassortant virus with PR8 M gene displayed higher pathogenicity when compared to the Bat09:mH1mN1 virus. This is most likely due to the fact that the PR8 H1N1 virus is a mouse-adapted virus. Furthermore, reassortment potential between the Bat09:mH1mN1 virus and an H3N2 swine influenza virus (A/swine/Texas/4199-2/1998) was investigated using co-infection of MDCK cells, but no reassortant viruses were detected. Taken together, our results indicate that the modified bat influenza virus is most likely incapable of reassortment with influenza A viruses with in vitro co-infection experiments, although reassortant viruses with different M genes can be generated by reverse genetics.

  20. Commensal Viruses of Mosquitoes: Host Restriction, Transmission, and Interaction with Arboviral Pathogens

    PubMed Central

    Hall, Roy A.; Bielefeldt-Ohmann, Helle; McLean, Breeanna J.; O’Brien, Caitlin A.; Colmant, Agathe M.G.; Piyasena, Thisun B.H.; Harrison, Jessica J.; Newton, Natalee D.; Barnard, Ross T.; Prow, Natalie A.; Deerain, Joshua M.; Mah, Marcus G.K.Y.; Hobson-Peters, Jody

    2016-01-01

    Recent advances in virus detection strategies and deep sequencing technologies have enabled the identification of a multitude of new viruses that persistently infect mosquitoes but do not infect vertebrates. These are usually referred to as insect-specific viruses (ISVs). These novel viruses have generated considerable interest in their modes of transmission, persistence in mosquito populations, the mechanisms that restrict their host range to mosquitoes, and their interactions with pathogens transmissible by the same mosquito. In this article, we discuss studies in our laboratory and others that demonstrate that many ISVs are efficiently transmitted directly from the female mosquito to their progeny via infected eggs, and, moreover, that persistent infection of mosquito cell cultures or whole mosquitoes with ISVs can restrict subsequent infection, replication, and transmission of some mosquito-borne viral pathogens. This suggests that some ISVs may act as natural regulators of arboviral transmission. We also discuss viral and host factors that may be responsible for their host restriction. PMID:28096646

  1. Poultry vaccination directed evolution of H9N2 low pathogenicity avian influenza viruses in Korea

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Significant economic losses in the poultry industries have resulted from H9N2 low pathogenic avian influenza virus infections across North Africa, the Middle East and Asia. The present study investigated the evolutionary dynamics of H9N2 viruses circulating in Korea from 1996 to 2012. Our analysis o...

  2. Rapidly Expanding Range of Highly Pathogenic Avian Influenza Viruses.

    PubMed

    Hall, Jeffrey S; Dusek, Robert J; Spackman, Erica

    2015-07-01

    The movement of highly pathogenic avian influenza (H5N8) virus across Eurasia and into North America and the virus' propensity to reassort with co-circulating low pathogenicity viruses raise concerns among poultry producers, wildlife biologists, aviculturists, and public health personnel worldwide. Surveillance, modeling, and experimental research will provide the knowledge required for intelligent policy and management decisions.

  3. 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...

  4. 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.

  5. Recovery of Pathogenic Measles Virus from Cloned cDNA

    PubMed Central

    Takeda, Makoto; Takeuchi, Kaoru; Miyajima, Naoko; Kobune, Fumio; Ami, Yasushi; Nagata, Noriyo; Suzaki, Yuriko; Nagai, Yoshiyuki; Tashiro, Masato

    2000-01-01

    Reverse genetics technology so far established for measles virus (MeV) is based on the Edmonston strain, which was isolated several decades ago, has been passaged in nonlymphoid cell lines, and is no longer pathogenic in monkey models. On the other hand, MeVs isolated and passaged in the Epstein-Barr virus-transformed marmoset B-lymphoblastoid cell line B95a would retain their original pathogenicity (F. Kobune et al., J. Virol. 64:700–705, 1990). Here we have developed MeV reverse genetics systems based on the highly pathogenic IC-B strain isolated in B95a cells. Infectious viruses were successfully recovered from the cloned cDNA of IC-B strain by two different approaches. One was simple cotransfection of B95a cells, with three plasmids each encoding the nucleocapsid (N), phospho (P), or large (L) protein, respectively, and their expression was driven by the bacteriophage T7 RNA polymerase supplied by coinfecting recombinant vaccinia virus vTF7-3. The second approach was transfection with the L-encoding plasmid of a helper cell line constitutively expressing the MeV N and P proteins and the T7 polymerase (F. Radecke et al., EMBO J. 14:5773–5784, 1995) on which B95a cells were overlaid. Virus clones recovered by both methods possessed RNA genomes identical to that of the parental IC-B strain and were indistinguishable from the IC-B strain with respect to growth phenotypes in vitro and the clinical course and histopathology of experimentally infected cynomolgus monkeys. Thus, the systems developed here could be useful for studying viral gene functions in the context of the natural course of MeV pathogenesis. PMID:10864679

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

    PubMed

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

    2017-04-15

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

  7. Microgravity Analogues of Herpes Virus Pathogenicity: Human Cytomegalovirus (hCMV) and Varicella Zoster (VZV) Infectivity in Human Tissue Like Assemblies (TLAs)

    NASA Technical Reports Server (NTRS)

    Goodwin, T. J.; McCarthy, M.; Albrecht, T.; Cohrs, R.

    2009-01-01

    The old adage we are our own worst enemies may perhaps be the most profound statement ever made when applied to man s desire for extraterrestrial exploration and habitation of Space. Consider the immune system protects the integrity of the entire human physiology and is comprised of two basic elements the adaptive or circulating and the innate immune system. Failure of the components of the adaptive system leads to venerability of the innate system from opportunistic microbes; viral, bacteria, and fungal, which surround us, are transported on our skin, and commonly inhabit the human physiology as normal and imunosuppressed parasites. The fine balance which is maintained for the preponderance of our normal lives, save immune disorders and disease, is deregulated in microgravity. Thus analogue systems to study these potential Risks are essential for our progress in conquering Space exploration and habitation. In this study we employed two known physiological target tissues in which the reactivation of hCMV and VZV occurs, human neural and lung systems created for the study and interaction of these herpes viruses independently and simultaneously on the innate immune system. Normal human neural and lung tissue analogues called tissue like assemblies (TLAs) were infected with low MOIs of approximately 2 x 10(exp -5) pfu hCMV or VZV and established active but prolonged low grade infections which spanned .7-1.5 months in length. These infections were characterized by the ability to continuously produce each of the viruses without expiration of the host cultures. Verification and quantification of viral replication was confirmed via RT_PCR, IHC, and confocal spectral analyses of the respective essential viral genomes. All host TLAs maintained the ability to actively proliferate throughout the entire duration of the experiments as is analogous to normal in vivo physiological conditions. These data represent a significant advance in the ability to study the triggering

  8. Plasmopara halstedii virus causes hypovirulence in Plasmopara halstedii, the downy mildew pathogen of the sunflower.

    PubMed

    Grasse, Wolfgang; Zipper, Reinhard; Totska, Maria; Spring, Otmar

    2013-08-01

    Plasmopara halstedii virus (PhV) is an isometric virus recently found in the oomycete Plasmopara halstedii. The fully sequenced virus genome consists of two ss(+)RNA strands encoding for the virus polymerase and the coat protein, respectively. Most of previously screened field isolates of P. halstedii were found to harbor PhV, but effects of PhV on the pathogenicity and aggressiveness of the oomycete have not been investigated yet. To assess the influence of PhV on the infectivity of P. halstedii, virus-free isolates of the oomycete were searched for, cultivated on sunflower and used for single zoospore infection. Four genetically homogenous strains belonging to three different pathotypes (710, 730, 750) were established. Subcultures of each strain were successfully infected with PhV. This afforded pairs of isogenic strains with and without virus and allowed assessment of the pathogenicity (susceptibility to specific sunflower genotypes) and aggressiveness (intensity of infection, time scale and density of sporulation) in cultivation of sunflower. While no significant difference was found in the pathogenicity of P. halstedii strains with and without virus towards sunflower seedlings of different resistance (pathotype differentials), the aggressiveness of the oomycete was diminished by PhV. Compared to the virus-free strains, the time required for the first sporulation (latent period) increased by about 1 day post inoculation. Progression of the pathogen from the hypocotyl into the epicotyl of sunflower (systemic infection) was reduced by about one third in the presence of virus. In the virus containing strains, the average density of sporangia produced per cm² cotyledon reached only 75% of the virus-free controls. In summary, the presence of PhV leads to hypovirulence effects by weakening the aggressiveness of P. halstedii.

  9. 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

  10. 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

  11. Atypical pathogens and respiratory tract infections.

    PubMed

    Blasi, F

    2004-07-01

    The atypical respiratory pathogens Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila are now recognised as a significant cause of acute respiratory-tract infections, implicated in community-acquired pneumonia, acute exacerbations of chronic bronchitis, asthma, and less frequently, upper respiratory-tract infections. Chronic infection with C. pneumoniae is common among patients with chronic obstructive pulmonary disease and may also play a role in the natural history of asthma, including exacerbations. The lack of a gold standard for diagnosis of these pathogens still handicaps the current understanding of their true prevalence and role in the pathogenesis of acute and chronic respiratory infections. While molecular diagnostic techniques, such as polymerase chain reaction, offer improvements in sensitivity, specificity and rapidity over culture and serology, the need remains for a consistent and reproducible diagnostic technique, available to all microbiology laboratories. Current treatment guidelines for community-acquired pneumonia recognise the importance of atypical respiratory pathogens in its aetiology, for which macrolides are considered suitable first-line agents. The value of atypical coverage in antibiotic therapy for acute exacerbations of chronic bronchitis and exacerbations of asthma is less clear, while there is no evidence to suggest that atypical pathogens should be covered in antibiotic treatment of upper respiratory-tract infections.

  12. Airborne transmission of H5N1 high pathogenicity avian influenza viruses during simulated home slaughter

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Most H5N1 human infections have occurred following exposure to H5N1 high pathogenicity avian influenza (HPAI) virus-infected poultry, especially when poultry are home slaughtered or slaughtered in live poultry markets. Previous studies have demonstrated that slaughter of clade 1 isolate A/Vietnam/1...

  13. High pathogenicity avian influenza virus in the reproductive tract of chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Infection with high pathogenicity avian influenza virus (HPAIV) has been associated with a wide range of clinical manifestations in poultry including severe depression in egg production and isolation of HPAIV from eggs laid by infected hens. To evaluate the pathobiology in the reproductive tract of...

  14. Characterization of low-pathogenicity H5N1 avian influenza viruses from North America

    USGS Publications Warehouse

    Spackman, Erica; Swayne, David E.; Suarez, David L.; Senne, Dennis A.; Pedersen, Janice C.; Killian, Mary Lea; Pasick, John; Handel, Katherine; Somanathan Pillai, Smitha; Lee, Chang-Won; Stallknecht, David; Slemons, Richard; Ip, Hon S.; Deliberto, Tom

    2007-01-01

    Wild-bird surveillance in North America for avian influenza (AI) viruses with a goal of early identification of the Asian H5N1 highly pathogenic AI virus has identified at least six low-pathogenicity H5N1 AI viruses between 2004 and 2006. The hemagglutinin (HA) and neuraminidase (NA) genes from all 6 H5N1 viruses and an additional 38 North American wild-bird-origin H5 subtype and 28 N1 subtype viruses were sequenced and compared with sequences available in GenBank by phylogenetic analysis. Both HA and NA were phylogenetically distinct from those for viruses from outside of North America and from those for viruses recovered from mammals. Four of the H5N1 AI viruses were characterized as low pathogenicity by standard in vivo pathotyping tests. One of the H5N1 viruses, A/MuteSwan/MI/451072-2/06, was shown to replicate to low titers in chickens, turkeys, and ducks. However, transmission of A/MuteSwan/MI/451072-2/06 was more efficient among ducks than among chickens or turkeys based on virus shed. The 50% chicken infectious dose for A/MuteSwan/MI/451072-2/06 and three other wild-waterfowl-origin H5 viruses were also determined and were between 105.3 and 107.5 50% egg infective doses. Finally, seven H5 viruses representing different phylogenetic clades were evaluated for their antigenic relatedness by hemagglutination inhibition assay, showing that the antigenic relatedness was largely associated with geographic origin. Overall, the data support the conclusion that North American H5 wild-bird-origin AI viruses are low-pathogenicity wild-bird-adapted viruses and are antigenically and genetically distinct from the highly pathogenic Asian H5N1 virus lineage.

  15. Characterization of low-pathogenicity H5N1 avian influenza viruses from North America

    USGS Publications Warehouse

    Spackman, Erica; Swayne, D. E.; Suarez, D. L.; Senne, D. A.; Pedersen, J. C.; Killian, M. L.; Pasick, J.; Handel, K.; Pillai, S. P. S.; Lee, C. -W.; Stallknecht, D.; Slemons, R.; Ip, H. S.; Deliberto, T.

    2007-01-01

    Wild-bird surveillance in North America for avian influenza (AI) viruses with a goal of early identification of the Asian H5N1 highly pathogenic AI virus has identified at least six low-pathogenicity H5N1 AI viruses between 2004 and 2006. The hemagglutinin (HA) and neuraminidase (NA) genes from all 6 H5N1 viruses and an additional 38 North American wild-bird-origin H5 subtype and 28 N1 subtype viruses were sequenced and compared with sequences available in GenBank by phylogenetic analysis. Both HA and NA were phylogenetically distinct from those for viruses from outside of North America and from those for viruses recovered from mammals. Four of the H5N1 AI viruses were characterized as low pathogenicity by standard in vivo pathotyping tests. One of the H5N1 viruses, A/MuteSwan/MI/451072-2/06, was shown to replicate to low titers in chickens, turkeys, and ducks. However, transmission of A/MuteSwan/MI/451072-2/06 was more efficient among ducks than among chickens or turkeys based on virus shed. The 50% chicken infectious dose for A/MuteSwan/MI/451072-2/06 and three other wild-waterfowl-origin H5 viruses were also determined and were between 10 5.3 and 107.5 50% egg infective doses. Finally, seven H5 viruses representing different phylogenetic clades were evaluated for their antigenic relatedness by hemagglutination inhibition assay, showing that the antigenic relatedness was largely associated with geographic origin. Overall, the data support the conclusion that North American H5 wild-bird-origin AI viruses are low-pathogenicity wild-bird-adapted viruses and are antigenically and genetically distinct from the highly pathogenic Asian H5N1 virus lineage. Copyright ?? 2007, American Society for Microbiology. All Rights Reserved.

  16. 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).

  17. Pathogenic prion protein fragment (PrP106-126) promotes human immunodeficiency virus type-1 infection in peripheral blood monocyte-derived macrophages.

    PubMed

    Bacot, Silvia M; Feldman, Gerald M; Yamada, Kenneth M; Dhawan, Subhash

    2015-02-01

    Transfusion of blood and blood products contaminated with the pathogenic form of prion protein Prp(sc), thought to be the causative agent of variant a Creutzfeldt-Jakob disease (vCJD), may result in serious consequences in recipients with a compromised immune system, for example, as seen in HIV-1 infection. In the present study, we demonstrate that treatment of peripheral blood monocyte-derived macrophages (MDM) with PrP106-126, a synthetic domain of PrP(sc) that has intrinsic functional activities related to the full-length protein, markedly increased their susceptibility to HIV-1 infection, induced cytokine secretion, and enhanced their migratory behavior in response to N-formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLP). Live-cell imaging of MDM cultured in the presence of PrP106-126 showed large cell clusters indicative of cellular activation. Tyrosine kinase inhibitor STI-571, protein kinase C inhibitor K252B, and cyclin-dependent kinase inhibitor olomoucine attenuated PrP106-126-induced altered MDM functions. These findings delineate a previously undefined functional role of PrP106-126-mediated host cell response in promoting HIV-1 pathogenesis.

  18. Role for proteases and HLA-G in the pathogenicity of influenza A viruses.

    PubMed

    Foucault, Marie-Laure; Moules, Vincent; Rosa-Calatrava, Manuel; Riteau, Béatrice

    2011-07-01

    Influenza is one of the most common infectious diseases in humans occurring as seasonal epidemic and sporadic pandemic outbreaks. The ongoing infections of humans with avian H5N1 influenza A viruses (IAV) and the past 2009 pandemic caused by the quadruple human/avian/swine reassortant (H1N1) virus highlights the permanent threat caused by these viruses. This review aims to describe the interaction between the virus and the host, with a particular focus on the role of proteases and HLA-G in the pathogenicity of influenza viruses.

  19. Effect of species, breed and route of virus inoculation on the pathogenicity of H5N1 highly pathogenic influenza (HPAI) viruses in domestic ducks

    PubMed Central

    2013-01-01

    H5N1 highly pathogenic avian influenza (HPAI) viruses continue to be a threat to poultry in many regions of the world. Domestic ducks have been recognized as one of the primary factors in the spread of H5N1 HPAI. In this study we examined the pathogenicity of H5N1 HPAI viruses in different species and breeds of domestic ducks and the effect of route of virus inoculation on the outcome of infection. We determined that the pathogenicity of H5N1 HPAI viruses varies between the two common farmed duck species, with Muscovy ducks (Cairina moschata) presenting more severe disease than various breeds of Anas platyrhynchos var. domestica ducks including Pekin, Mallard-type, Black Runners, Rouen, and Khaki Campbell ducks. We also found that Pekin and Muscovy ducks inoculated with two H5N1 HPAI viruses of different virulence, given by any one of three routes (intranasal, intracloacal, or intraocular), became infected with the viruses. Regardless of the route of inoculation, the outcome of infection was similar for each species but depended on the virulence of the virus used. Muscovy ducks showed more severe clinical signs and higher mortality than the Pekin ducks. In conclusion, domestic ducks are susceptible to H5N1 HPAI virus infection by different routes of exposure, but the presentation of the disease varied by virus strain and duck species. This information helps support the planning and implementation of H5N1 HPAI surveillance and control measures in countries with large domestic duck populations. PMID:23876184

  20. Effect of species, breed and route of virus inoculation on the pathogenicity of H5N1 highly pathogenic influenza (HPAI) viruses in domestic ducks.

    PubMed

    Pantin-Jackwood, Mary; Swayne, David E; Smith, Diane; Shepherd, Eric

    2013-07-22

    H5N1 highly pathogenic avian influenza (HPAI) viruses continue to be a threat to poultry in many regions of the world. Domestic ducks have been recognized as one of the primary factors in the spread of H5N1 HPAI. In this study we examined the pathogenicity of H5N1 HPAI viruses in different species and breeds of domestic ducks and the effect of route of virus inoculation on the outcome of infection. We determined that the pathogenicity of H5N1 HPAI viruses varies between the two common farmed duck species, with Muscovy ducks (Cairina moschata) presenting more severe disease than various breeds of Anas platyrhynchos var. domestica ducks including Pekin, Mallard-type, Black Runners, Rouen, and Khaki Campbell ducks. We also found that Pekin and Muscovy ducks inoculated with two H5N1 HPAI viruses of different virulence, given by any one of three routes (intranasal, intracloacal, or intraocular), became infected with the viruses. Regardless of the route of inoculation, the outcome of infection was similar for each species but depended on the virulence of the virus used. Muscovy ducks showed more severe clinical signs and higher mortality than the Pekin ducks. In conclusion, domestic ducks are susceptible to H5N1 HPAI virus infection by different routes of exposure, but the presentation of the disease varied by virus strain and duck species. This information helps support the planning and implementation of H5N1 HPAI surveillance and control measures in countries with large domestic duck populations.

  1. Bronchointerstitial pneumonia in guinea pigs following inoculation with H5N1 high pathogenicity avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The H5N1 high pathogenicity avian influenza (HPAI) viruses have caused widespread disease of poultry in Asia, Africa and the Middle East, and sporadic human infections. The guinea pig model has been used to study human H3N2 and H1N1 influenza viruses, but knowledge is lacking on H5N1 HPAI virus inf...

  2. 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

  3. Genetic changes that accompanied shifts of low pathogenic avian influenza viruses toward higher pathogenicity in poultry

    PubMed Central

    Abdelwhab, El-Sayed M; Veits, Jutta; Mettenleiter, Thomas C

    2013-01-01

    Avian influenza viruses (AIV) of H5 and H7 subtypes exhibit two different pathotypes in poultry: infection with low pathogenic (LP) strains results in minimal, if any, health disturbances, whereas highly pathogenic (HP) strains cause severe morbidity and mortality. LPAIV of H5 and H7 subtypes can spontaneously mutate into HPAIV. Ten outbreaks caused by HPAIV are known to have been preceded by circulation of a predecessor LPAIV in poultry. Three of them were caused by H5N2 subtype and seven involved H7 subtype in combination with N1, N3, or N7. Here, we review those outbreaks and summarize the genetic changes which resulted in the transformation of LPAIV to HPAIV under natural conditions. Mutations that were found directly in those outbreaks are more likely to be linked to virulence, pathogenesis, and early adaptation of AIV. PMID:23863606

  4. Experimental infection of Muscovy ducks with highly pathogenic avian influenza virus (H5N1) belonging to clade 2.2.

    PubMed

    Guionie, Olivier; Guillou-Cloarec, Cécile; Courtois, David; Bougeard, B Stéphanie; Amelot, Michel; Jestin, Véronique

    2010-03-01

    Highly pathogenic (HP) H5N1 avian influenza (AI) is enzootic in several countries of Asia and Africa and constitutes a major threat, at the world level, for both animal and public health. Ducks play an important role in the epidemiology of AI, including HP H5N1 AI. Although vaccination can be a useful tool to control AI, duck vaccination has not proved very efficient in the field, indicating a need to develop new vaccines and a challenge model to evaluate the protection for duck species. Although Muscovy duck is the duck species most often reared in France, the primary duck-producing country in Europe, and is also produced in Asia, it is rarely studied. Our team recently demonstrated a good cross-reactivity with hemagglutinin from clade 2.2 and inferred that this could be a good vaccine candidate for ducks. Two challenges using two French H5N1 HP strains, 1) A/mute swan/France/06299/06 (Swan/06299), clade 2.2.1, and 2) A/mute swan/France/070203/07 (Swan/070203), clade 2.2 (but different from subclade 2.2.1), were performed (each) on 20 Muscovy ducks (including five contacts) inoculated by oculo-nasal route (6 log10 median egg infectious doses per duck). Clinical signs were recorded daily, and cloacal and oropharyngeal swabs were collected throughout the assay. Autopsies were done on all dead ducks, and organs were taken for analyses. Virus was measured by quantitative reverse transcriptase-PCR based on the M gene AI virus. Ducks presented severe nervous signs in both challenges. Swan/070203 strain led to 80% morbidity (12/15 sick ducks) and 73% mortality (11/15 ducks) at 13.5 days postinfection (dpi), whereas Swan/06299 strain produced 100% mortality at 6.5 dpi. Viral RNA load was significantly lower via the cloacal route than via the oropharyngeal route in both trials, presenting a peak in the first challenge at 3.5 dpi and being more stable in the second challenge. The brain was the organ containing the highest viral RNA load in both challenges. Viral RNA load in

  5. 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.

  6. 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

  7. 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.

  8. Rapidly expanding range of highly pathogenic avian influenza viruses

    USGS Publications Warehouse

    Hall, Jeffrey S.; Dusek, Robert J.; Spackman, Erica

    2015-01-01

    The movement of highly pathogenic avian influenza (H5N8) virus across Eurasia and into North America and the virus’ propensity to reassort with co-circulating low pathogenicity viruses raise concerns among poultry producers, wildlife biologists, aviculturists, and public health personnel worldwide. Surveillance, modeling, and experimental research will provide the knowledge required for intelligent policy and management decisions.

  9. 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.

  10. 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.

  11. 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

  12. Pathogenicity of the Korean H5N8 highly pathogenic avian influenza virus in commercial domestic poultry species.

    PubMed

    Lee, Dong-Hun; Kwon, Jung-Hoon; Noh, Jin-Yong; Park, Jae-Keun; Yuk, Seong-Su; Erdene-Ochir, Tseren-Ochir; Lee, Joong-Bok; Park, Seung-Yong; Choi, In-Soo; Lee, Sang-Won; Song, Chang-Seon

    2016-01-01

    In 2014, the highly pathogenic avian influenza (HPAI) virus H5N8 triggered outbreaks in wild birds and poultry farms in South Korea. In the present study, we investigated the pathogenicity of the H5N8 HPAI virus, belonging to the clade 2.3.4.4, in different species of poultry. For this, we examined clinical signs and viral shedding levels following intranasal inoculation of the virus in 3-week-old commercial layer chickens and quails, 10-week-old Korean native chickens, and 8-week-old Muscovy ducks. Intranasal inoculation with 10(6.0) viruses at 50% egg-infective dose resulted in 100% mortality in the layer chickens (8/8) and quails (4/4), but 60% and 0% deaths in the Korean native chickens (3/5) and Muscovy ducks (0/4), respectively. In addition, transmission of the inoculated virus to contact-exposed birds was evident in all the species used in this study. Based on our results, we conclude that the H5N8 HPAI virus has lower pathogenicity and transmissibility in poultry species compared with previously reported H5N1 HPAI viruses.

  13. Differential immune response of mallard duck peripheral blood mononuclear cells to two highly pathogenic avian influenza H5N1 viruses with distinct pathogenicity in mallard ducks.

    PubMed

    Cui, Zhu; Hu, Jiao; He, Liang; Li, Qunhui; Gu, Min; Wang, Xiaoquan; Hu, Shunlin; Liu, Huimou; Liu, Wenbo; Liu, Xiaowen; Liu, Xiufan

    2014-02-01

    CK10 and GS10 are two H5N1 highly pathogenic influenza viruses of similar genetic background but differ in their pathogenicity in mallard ducks. CK10 is highly pathogenic whereas GS10 is low pathogenic. In this study, strong inflammatory response in terms of the expression level of several cytokines was observed in mallard duck peripheral blood mononuclear cells (PBMC) infected with CK10 while mild response was triggered in those by GS10 infection. Two remarkable and intense peaks of immune response were induced by CK10 infection within 24 hours (at 8 and 24 hours post infection, respectively) without reducing the virus replication. Our observations indicated that sustained and intense innate immune responses may be central to the high pathogenicity caused by CK10 in ducks.

  14. Immediate early responses of avian tracheal epithelial cells to infection with highly pathogenic avian influenza

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Highly pathogenic (HP) avian influenza viruses (AIV) present an on going threat to the U.S. poultry industry. In order to develop new AIV control strategies it is necessary to understand the underlying mechanism of viral infection. Because the early events of AIV infection can occur on tracheal ep...

  15. 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

  16. 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.

  17. Recombinant Vaccinia Virus: Immunization against Multiple Pathogens

    NASA Astrophysics Data System (ADS)

    Perkus, Marion E.; Piccini, Antonia; Lipinskas, Bernard R.; Paoletti, Enzo

    1985-09-01

    The coding sequences for the hepatitis B virus surface antigen, the herpes simplex virus glycoprotein D, and the influenza virus hemagglutinin were inserted into a single vaccinia virus genome. Rabbits inoculated intravenously or intradermally with this polyvalent vaccinia virus recombinant produced antibodies reactive to all three authentic foreign antigens. In addition, the feasibility of multiple rounds of vaccination with recombinant vaccinia virus was demonstrated.

  18. 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

  19. In vivo replication of pathogenic and attenuated strains of Junin virus in different cell populations of lymphatic tissue.

    PubMed Central

    Laguens, M; Chambó, J G; Laguens, R P

    1983-01-01

    Lymphatic tissue is one of the main sites for replication of Junin virus. To characterize which cells are involved in that replication, the presence of Junin virus in purified populations of macrophages and dendritic cells from the spleens of guinea pigs infected with pathogenic and attenuated strains was investigated by immunofluorescence and intracerebral inoculation into newborn mice. The pathogenic strain was present both in macrophages and in dendritic cells, but the attenuated strain selectively infected dendritic cells. These observations suggest that the pathogenic behavior and replication efficiency of these two strains of Junin virus may be related to a difference in cell targets. Images PMID:6309667

  20. 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.

  1. 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.

  2. Infection of Murine Macrophages by Salmonella enterica Serovar Heidelberg Blocks Murine Norovirus Infectivity and Virus-induced Apoptosis.

    PubMed

    Agnihothram, Sudhakar S; Basco, Maria D S; Mullis, Lisa; Foley, Steven L; Hart, Mark E; Sung, Kidon; Azevedo, Marli P

    2015-01-01

    Gastroenteritis caused by bacterial and viral pathogens constitutes a major public health threat in the United States accounting for 35% of hospitalizations. In particular, Salmonella enterica and noroviruses cause the majority of gastroenteritis infections, with emergence of sporadic outbreaks and incidence of increased infections. Although mechanisms underlying infections by these pathogens have been individually studied, little is known about the mechanisms regulating co-infection by these pathogens. In this study, we utilized RAW 264.7 murine macrophage cells to investigate the mechanisms governing co-infection with S. enterica serovar Heidelberg and murine norovirus (MNV). We demonstrate that infection of RAW 264.7 cells with S. enterica reduces the replication of MNV, in part by blocking virus entry early in the virus life cycle, and inducing antiviral cytokines later in the infection cycle. In particular, bacterial infection prior to, or during MNV infection affected virus entry, whereas MNV entry remained unaltered when the virus infection preceded bacterial invasion. This block in virus entry resulted in reduced virus replication, with the highest impact on replication observed during conditions of co-infection. In contrast, bacterial replication showed a threefold increase in MNV-infected cells, despite the presence of antibiotic in the medium. Most importantly, we present evidence that the infection of MNV-infected macrophages by S. enterica blocked MNV-induced apoptosis, despite allowing efficient virus replication. This apoptosis blockade was evidenced by reduction in DNA fragmentation and absence of poly-ADP ribose polymerase (PARP), caspase 3 and caspase 9 cleavage events. Our study suggests a novel mechanism of pathogenesis whereby initial co-infection with these pathogens could result in prolonged infection by either of these pathogens or both together.

  3. Differential Adsorption of Occluded and Nonoccluded Insect-Pathogenic Viruses to Soil-Forming Minerals

    PubMed Central

    Christian, Peter D.; Richards, Andrew R.; Williams, Trevor

    2006-01-01

    Soil represents the principal environmental reservoir of many insect-pathogenic viruses. We compared the adsorption and infectivity of one occluded and two nonoccluded viruses, Helicoverpa armigera single nucleopolyhedrovirus (HaSNPV) (Baculoviridae), Cricket paralysis virus (CrPV) (Dicistroviridae), and Invertebrate iridescent virus 6 (IIV-6) (Iridoviridae), respectively, in mixtures with a selection of soil-forming minerals. The relative infective titers of HaSNPV and CrPV were unchanged or slightly reduced in the presence of different minerals compared to their titers in the absence of the mineral. In contrast, the infective titer of IIV-6 varied according to the mineral being tested. In adsorption studies, over 98% of HaSNPV occlusion bodies were adsorbed by all the minerals, and a particularly high affinity was observed with ferric oxide, attapulgite, and kaolinite. In contrast, the adsorption of CrPV and IIV-6 differed markedly with mineral type, with low affinity to bentonites and high affinity to ferric oxide and kaolinite. We conclude that interactions between soil-forming minerals and insect viruses appear to be most important in nucleopolyhedroviruses, followed by invertebrate iridescent viruses, and least important in CrPV, which may reflect the ecology of these pathogens. Moreover, soils with a high content of iron oxides or kaolinite would likely represent highly effective reservoirs for insect-pathogenic viruses. PMID:16820456

  4. Is There Still Room for Novel Viral Pathogens in Pediatric Respiratory Tract Infections?

    PubMed Central

    Taboada, Blanca; Espinoza, Marco A.; Isa, Pavel; Aponte, Fernando E.; Arias-Ortiz, María A.; Monge-Martínez, Jesús; Rodríguez-Vázquez, Rubén; Díaz-Hernández, Fidel; Zárate-Vidal, Fernando; Wong-Chew, Rosa María; Firo-Reyes, Verónica; del Río-Almendárez, Carlos N.; Gaitán-Meza, Jesús; Villaseñor-Sierra, Alberto; Martínez-Aguilar, Gerardo; Salas-Mier, Ma. del Carmen; Noyola, Daniel E.; Pérez-Gónzalez, Luis F.; López, Susana; Santos-Preciado, José I.; Arias, Carlos F.

    2014-01-01

    Viruses are the most frequent cause of respiratory disease in children. However, despite the advanced diagnostic methods currently in use, in 20 to 50% of respiratory samples a specific pathogen cannot be detected. In this work, we used a metagenomic approach and deep sequencing to examine respiratory samples from children with lower and upper respiratory tract infections that had been previously found negative for 6 bacteria and 15 respiratory viruses by PCR. Nasal washings from 25 children (out of 250) hospitalized with a diagnosis of pneumonia and nasopharyngeal swabs from 46 outpatient children (out of 526) were studied. DNA reads for at least one virus commonly associated to respiratory infections was found in 20 of 25 hospitalized patients, while reads for pathogenic respiratory bacteria were detected in the remaining 5 children. For outpatients, all the samples were pooled into 25 DNA libraries for sequencing. In this case, in 22 of the 25 sequenced libraries at least one respiratory virus was identified, while in all other, but one, pathogenic bacteria were detected. In both patient groups reads for respiratory syncytial virus, coronavirus-OC43, and rhinovirus were identified. In addition, viruses less frequently associated to respiratory infections were also found. Saffold virus was detected in outpatient but not in hospitalized children. Anellovirus, rotavirus, and astrovirus, as well as several animal and plant viruses were detected in both groups. No novel viruses were identified. Adding up the deep sequencing results to the PCR data, 79.2% of 250 hospitalized and 76.6% of 526 ambulatory patients were positive for viruses, and all other children, but one, had pathogenic respiratory bacteria identified. These results suggest that at least in the type of populations studied and with the sampling methods used the odds of finding novel, clinically relevant viruses, in pediatric respiratory infections are low. PMID:25412469

  5. 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

  6. Invasive ants carry novel viruses in their new range and form reservoirs for a honeybee pathogen

    PubMed Central

    Sébastien, Alexandra; Lester, Philip J.; Hall, Richard J.; Wang, Jing; Moore, Nicole E.; Gruber, Monica A. M.

    2015-01-01

    When exotic animal species invade new environments they also bring an often unknown microbial diversity, including pathogens. We describe a novel and widely distributed virus in one of the most globally widespread, abundant and damaging invasive ants (Argentine ants, Linepithema humile). The Linepithema humile virus 1 is a dicistrovirus, a viral family including species known to cause widespread arthropod disease. It was detected in samples from Argentina, Australia and New Zealand. Argentine ants in New Zealand were also infected with a strain of Deformed wing virus common to local hymenopteran species, which is a major pathogen widely associated with honeybee mortality. Evidence for active replication of viral RNA was apparent for both viruses. Our results suggest co-introduction and exchange of pathogens within local hymenopteran communities. These viral species may contribute to the collapse of Argentine ant populations and offer new options for the control of a globally widespread invader. PMID:26562935

  7. Aquatic eutrophication promotes pathogenic infection in amphibians.

    PubMed

    Johnson, Pieter T J; Chase, Jonathan M; Dosch, Katherine L; Hartson, Richard B; Gross, Jackson A; Larson, Don J; Sutherland, Daniel R; Carpenter, Stephen R

    2007-10-02

    The widespread emergence of human and wildlife diseases has challenged ecologists to understand how large-scale agents of environmental change affect host-pathogen interactions. Accelerated eutrophication of aquatic ecosystems owing to nitrogen and phosphorus enrichment is a pervasive form of environmental change that has been implicated in the emergence of diseases through direct and indirect pathways. We provide experimental evidence linking eutrophication and disease in a multihost parasite system. The trematode parasite Ribeiroia ondatrae sequentially infects birds, snails, and amphibian larvae, frequently causing severe limb deformities and mortality. Eutrophication has been implicated in the emergence of this parasite, but definitive evidence, as well as a mechanistic understanding, have been lacking until now. We show that the effects of eutrophication cascade through the parasite life cycle to promote algal production, the density of snail hosts, and, ultimately, the intensity of infection in amphibians. Infection also negatively affected the survival of developing amphibians. Mechanistically, eutrophication promoted amphibian disease through two distinctive pathways: by increasing the density of infected snail hosts and by enhancing per-snail production of infectious parasites. Given forecasted increases in global eutrophication, amphibian extinctions, and similarities between Ribeiroia and important human and wildlife pathogens, our results have broad epidemiological and ecological significance.

  8. Use of ultrafiltration to isolate viruses from seawater which are pathogens of marine phytoplankton.

    PubMed

    Suttle, C A; Chan, A M; Cottrell, M T

    1991-03-01

    Viruses may be major structuring elements of phytoplankton communities and hence important regulators of nutrient and energy fluxes in aquatic environments. In order to ascertain whether viruses are potentially important in dictating phytoplankton community structure, it is essential to determine the extent to which representative phytoplankton taxa are susceptible to viral infection. We used a spiral ultrafiltration cartridge (30,000-molecular-weight cutoff) to concentrate viruses from seawater at efficiencies approaching 100%. Natural virus communities were concentrated from stations in the Gulf of Mexico, a barrier island pass, and a hypersaline lagoon (Laguna Madre) and added to cultures of potential phytoplankton hosts. By following changes in in vivo fluorescence over time, it was possible to isolate several viruses that were pathogens to a variety of marine phytoplankton, including a prasinophyte (Micromonas pusilla), a pennate diatom (likely a Navicula sp.), a centric diatom (of unknown taxa), and a chroococcoid cyanobacterium (a Synechococcus sp.). As well, we observed changes in fluorescence in cultures of a cryptophyte (a Rhodomonas sp.) and a chlorophyte (Nannochloropsis oculata) which were consistent with the presence of viral pathogens. Although pathogens were isolated from all stations, all the pathogens were not isolated from every station. Filterability studies on the viruses infecting M. pusilla and the Navicula sp. showed that the viruses were consistently infective after filtration through polycarbonate and glass-fiber filters but were affected by most other filter types. Establishment of phytoplankton-pathogen systems will be important in elucidating the effect that viruses have on primary producers in aquatic systems.

  9. Newly Emergent Highly Pathogenic H5N9 Subtype Avian Influenza A Virus

    PubMed Central

    Yu, Yang; Wang, Xingbo; Jin, Tao; Wang, Hailong; Si, Weiying; Yang, Hui; Wu, Jiusheng; Yan, Yan; Liu, Guang; Sang, Xiaoyu; Wu, Xiaopeng; Gao, Yuwei; Xia, Xianzhu; Yu, Xinfen; Pan, Jingcao; Gao, George F.

    2015-01-01

    ABSTRACT The novel H7N9 avian influenza virus (AIV) was demonstrated to cause severe human respiratory infections in China. Here, we examined poultry specimens from live bird markets linked to human H7N9 infection in Hangzhou, China. Metagenomic sequencing revealed mixed subtypes (H5, H7, H9, N1, N2, and N9). Subsequently, AIV subtypes H5N9, H7N9, and H9N2 were isolated. Evolutionary analysis showed that the hemagglutinin gene of the novel H5N9 virus originated from A/Muscovy duck/Vietnam/LBM227/2012 (H5N1), which belongs to clade 2.3.2.1. The neuraminidase gene of the novel H5N9 virus originated from human-infective A/Hangzhou/1/2013 (H7N9). The six internal genes were similar to those of other H5N1, H7N9, and H9N2 virus strains. The virus harbored the PQRERRRKR/GL motif characteristic of highly pathogenic AIVs at the HA cleavage site. Receptor-binding experiments demonstrated that the virus binds α-2,3 sialic acid but not α-2,6 sialic acid. Identically, pathogenicity experiments also showed that the virus caused low mortality rates in mice. This newly isolated H5N9 virus is a highly pathogenic reassortant virus originating from H5N1, H7N9, and H9N2 subtypes. Live bird markets represent a potential transmission risk to public health and the poultry industry. IMPORTANCE This investigation confirms that the novel H5N9 subtype avian influenza A virus is a reassortant strain originating from H5N1, H7N9, and H9N2 subtypes and is totally different from the H5N9 viruses reported before. The novel H5N9 virus acquired a highly pathogenic H5 gene and an N9 gene from human-infecting subtype H7N9 but caused low mortality rates in mice. Whether this novel H5N9 virus will cause human infections from its avian host and become a pandemic subtype is not known yet. It is therefore imperative to assess the risk of emergence of this novel reassortant virus with potential transmissibility to public health. PMID:26085150

  10. 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.

  11. 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.

  12. 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

  13. Structure of deformed wing virus, a major honey bee pathogen

    PubMed Central

    Škubník, Karel; Nováček, Jiří; Füzik, Tibor; Přidal, Antonín; Paxton, Robert J.; Plevka, Pavel

    2017-01-01

    The worldwide population of western honey bees (Apis mellifera) is under pressure from habitat loss, environmental stress, and pathogens, particularly viruses that cause lethal epidemics. Deformed wing virus (DWV) from the family Iflaviridae, together with its vector, the mite Varroa destructor, is likely the major threat to the world’s honey bees. However, lack of knowledge of the atomic structures of iflaviruses has hindered the development of effective treatments against them. Here, we present the virion structures of DWV determined to a resolution of 3.1 Å using cryo-electron microscopy and 3.8 Å by X-ray crystallography. The C-terminal extension of capsid protein VP3 folds into a globular protruding (P) domain, exposed on the virion surface. The P domain contains an Asp-His-Ser catalytic triad that is, together with five residues that are spatially close, conserved among iflaviruses. These residues may participate in receptor binding or provide the protease, lipase, or esterase activity required for entry of the virus into a host cell. Furthermore, nucleotides of the DWV RNA genome interact with VP3 subunits. The capsid protein residues involved in the RNA binding are conserved among honey bee iflaviruses, suggesting a putative role of the genome in stabilizing the virion or facilitating capsid assembly. Identifying the RNA-binding and putative catalytic sites within the DWV virion structure enables future analyses of how DWV and other iflaviruses infect insect cells and also opens up possibilities for the development of antiviral treatments. PMID:28270616

  14. Structure of deformed wing virus, a major honey bee pathogen.

    PubMed

    Škubník, Karel; Nováček, Jiří; Füzik, Tibor; Přidal, Antonín; Paxton, Robert J; Plevka, Pavel

    2017-03-21

    The worldwide population of western honey bees (Apis mellifera) is under pressure from habitat loss, environmental stress, and pathogens, particularly viruses that cause lethal epidemics. Deformed wing virus (DWV) from the family Iflaviridae, together with its vector, the mite Varroa destructor, is likely the major threat to the world's honey bees. However, lack of knowledge of the atomic structures of iflaviruses has hindered the development of effective treatments against them. Here, we present the virion structures of DWV determined to a resolution of 3.1 Å using cryo-electron microscopy and 3.8 Å by X-ray crystallography. The C-terminal extension of capsid protein VP3 folds into a globular protruding (P) domain, exposed on the virion surface. The P domain contains an Asp-His-Ser catalytic triad that is, together with five residues that are spatially close, conserved among iflaviruses. These residues may participate in receptor binding or provide the protease, lipase, or esterase activity required for entry of the virus into a host cell. Furthermore, nucleotides of the DWV RNA genome interact with VP3 subunits. The capsid protein residues involved in the RNA binding are conserved among honey bee iflaviruses, suggesting a putative role of the genome in stabilizing the virion or facilitating capsid assembly. Identifying the RNA-binding and putative catalytic sites within the DWV virion structure enables future analyses of how DWV and other iflaviruses infect insect cells and also opens up possibilities for the development of antiviral treatments.

  15. Comparative Epidemiology of Human Fatal Infections with Novel, High (H5N6 and H5N1) and Low (H7N9 and H9N2) Pathogenicity Avian Influenza A Viruses

    PubMed Central

    Wu, Zu-Qun; Zhang, Yi; Zhao, Na; Yu, Zhao; Pan, Hao; Chan, Ta-Chien; Zhang, Zhi-Ruo; Liu, She-Lan

    2017-01-01

    This study aimed to assess the mortality risks for human infection with high (HPAI) and low (LPAI) pathogenicity avian influenza viruses. The HPAI case fatality rate (CFR) was far higher than the LPAI CFR [66.0% (293/444) vs. 68.75% (11/16) vs. 40.4% (265/656) vs. 0.0% (0/18) in the cases with H5N1, H5N6, H7N9, and H9N2 viruses, respectively; p < 0.001]. Similarly, the CFR of the index cases was greater than the secondary cases with H5N1 [100% (43/43) vs. 43.3% (42/97), p < 0.001]. Old age [22.5 vs. 17 years for H5N1, p = 0.018; 61 vs. 49 years for H7H9, p < 0.001], concurrent diseases [18.8% (15/80) vs. 8.33% (9/108) for H5N1, p = 0.046; 58.6% (156/266) vs. 34.8% (135/388) for H7H9, p < 0.001], delayed confirmation [13 vs. 6 days for H5N1, p < 0.001; 10 vs. 8 days for H7N9, p = 0.011] in the fatalities and survivors, were risk factors for deaths. With regard to the H5N1 clusters, exposure to poultry [67.4% (29/43) vs. 45.2% (19/42), p = 0.039] was the higher risk for the primary than the secondary deaths. In conclusion, old age, comorbidities, delayed confirmation, along with poultry exposure are the major risks contributing to fatal outcomes in human HPAI and LPAI infections. PMID:28273867

  16. Viruses of Fish: An Overview of Significant Pathogens

    PubMed Central

    Crane, Mark; Hyatt, Alex

    2011-01-01

    The growing global demand for seafood together with the limited capacity of the wild-capture sector to meet this demand has seen the aquaculture industry continue to grow around the world. A vast array of aquatic animal species is farmed in high density in freshwater, brackish and marine systems where they are exposed to new environments and potentially new diseases. On-farm stresses may compromise their ability to combat infection, and farming practices facilitate rapid transmission of disease. Viral pathogens, whether they have been established for decades or whether they are newly emerging as disease threats, are particularly challenging since there are few, if any, efficacious treatments, and the development of effective viral vaccines for delivery in aquatic systems remains elusive. Here, we review a few of the more significant viral pathogens of finfish, including aquabirnaviruses and infectious hematopoietic necrosis virus which have been known since the first half of the 20th century, and more recent viral pathogens, for example betanodaviruses, that have emerged as aquaculture has undergone a dramatic expansion in the past few decades. PMID:22163333

  17. Viruses of fish: an overview of significant pathogens.

    PubMed

    Crane, Mark; Hyatt, Alex

    2011-11-01

    The growing global demand for seafood together with the limited capacity of the wild-capture sector to meet this demand has seen the aquaculture industry continue to grow around the world. A vast array of aquatic animal species is farmed in high density in freshwater, brackish and marine systems where they are exposed to new environments and potentially new diseases. On-farm stresses may compromise their ability to combat infection, and farming practices facilitate rapid transmission of disease. Viral pathogens, whether they have been established for decades or whether they are newly emerging as disease threats, are particularly challenging since there are few, if any, efficacious treatments, and the development of effective viral vaccines for delivery in aquatic systems remains elusive. Here, we review a few of the more significant viral pathogens of finfish, including aquabirnaviruses and infectious hematopoietic necrosis virus which have been known since the first half of the 20th century, and more recent viral pathogens, for example betanodaviruses, that have emerged as aquaculture has undergone a dramatic expansion in the past few decades.

  18. Two novel viruses associated with the Apis mellifera pathogenic mite Varroa destructor.

    PubMed

    Levin, Sofia; Sela, Noa; Chejanovsky, Nor

    2016-11-24

    Varroa destructor infestation of Apis mellifera colonies carries and/or promotes replication of honey bee viruses like the Deformed wing virus, the Varroa destructor virus-1, the Acute bee paralysis virus, the Israeli acute bee paralysis virus and the Kashmir bee virus that have been well described and characterized; but viruses exclusively associated with Varroa were not found. To look for viruses that may associate with- or infect V. destructor we performed deep sequencing (RNA-seq) of RNA extracted from honey bees and mites in Varroa-infested untreated colonies. Comparative bioinformatic analysis of the two separate contig-assemblies generated from the sequences' reads annotated using Blastx enabled identification of new viruses unique to Varroa and absent in A. mellifera: an Iflavirus and a virus with homology to Ixodes scapularis associated virus 2, that we named Varroa destructor virus 2 (VDV-2) and 3(VDV-3), respectively. We validated these findings sequencing the mite- and honey bee-viromes and in separate mites and honey bees randomly sampled. The complete genomes of VDV-2 and VDV-3 bear 9576 nucleotides and 4202 nucleotides, respectively. Phylogenetic analysis of VDV-3 suggests that it belongs to a new group of viruses. Our results open venues for investigating the pathogenicity of these V. destructor viruses.

  19. Two novel viruses associated with the Apis mellifera pathogenic mite Varroa destructor

    PubMed Central

    Levin, Sofia; Sela, Noa; Chejanovsky, Nor

    2016-01-01

    Varroa destructor infestation of Apis mellifera colonies carries and/or promotes replication of honey bee viruses like the Deformed wing virus, the Varroa destructor virus-1, the Acute bee paralysis virus, the Israeli acute bee paralysis virus and the Kashmir bee virus that have been well described and characterized; but viruses exclusively associated with Varroa were not found. To look for viruses that may associate with- or infect V. destructor we performed deep sequencing (RNA-seq) of RNA extracted from honey bees and mites in Varroa-infested untreated colonies. Comparative bioinformatic analysis of the two separate contig-assemblies generated from the sequences’ reads annotated using Blastx enabled identification of new viruses unique to Varroa and absent in A. mellifera: an Iflavirus and a virus with homology to Ixodes scapularis associated virus 2, that we named Varroa destructor virus 2 (VDV-2) and 3(VDV-3), respectively. We validated these findings sequencing the mite- and honey bee-viromes and in separate mites and honey bees randomly sampled. The complete genomes of VDV-2 and VDV-3 bear 9576 nucleotides and 4202 nucleotides, respectively. Phylogenetic analysis of VDV-3 suggests that it belongs to a new group of viruses. Our results open venues for investigating the pathogenicity of these V. destructor viruses. PMID:27883042

  20. Severity of Bovine Tuberculosis Is Associated with Co-Infection with Common Pathogens in Wild Boar

    PubMed Central

    Risco, David; Serrano, Emmanuel; Fernández-Llario, Pedro; Cuesta, Jesús M.; Gonçalves, Pilar; García-Jiménez, Waldo L.; Martínez, Remigio; Cerrato, Rosario; Velarde, Roser; Gómez, Luis; Segalés, Joaquím; Hermoso de Mendoza, Javier

    2014-01-01

    Co-infections with parasites or viruses drive tuberculosis dynamics in humans, but little is known about their effects in other non-human hosts. This work aims to investigate the relationship between Mycobacterium bovis infection and other pathogens in wild boar (Sus scrofa), a recognized reservoir of bovine tuberculosis (bTB) in Mediterranean ecosystems. For this purpose, it has been assessed whether contacts with common concomitant pathogens are associated with the development of severe bTB lesions in 165 wild boar from mid-western Spain. The presence of bTB lesions affecting only one anatomic location (cervical lymph nodes), or more severe patterns affecting more than one location (mainly cervical lymph nodes and lungs), was assessed in infected animals. In addition, the existence of contacts with other pathogens such as porcine circovirus type 2 (PCV2), Aujeszky's disease virus (ADV), swine influenza virus, porcine reproductive and respiratory syndrome virus, Mycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae, Haemophilus parasuis and Metastrongylus spp, was evaluated by means of serological, microbiological and parasitological techniques. The existence of contacts with a structured community of pathogens in wild boar infected by M. bovis was statistically investigated by null models. Association between this community of pathogens and bTB severity was examined using a Partial Least Squares regression approach. Results showed that adult wild boar infected by M. bovis had contacted with some specific, non-random pathogen combinations. Contact with PCV2, ADV and infection by Metastrongylus spp, was positively correlated to tuberculosis severity. Therefore, measures against these concomitant pathogens such as vaccination or deworming, might be useful in tuberculosis control programmes in the wild boar. However, given the unexpected consequences of altering any community of organisms, further research should evaluate the impact of such measures under

  1. Severity of bovine tuberculosis is associated with co-infection with common pathogens in wild boar.

    PubMed

    Risco, David; Serrano, Emmanuel; Fernández-Llario, Pedro; Cuesta, Jesús M; Gonçalves, Pilar; García-Jiménez, Waldo L; Martínez, Remigio; Cerrato, Rosario; Velarde, Roser; Gómez, Luis; Segalés, Joaquím; Hermoso de Mendoza, Javier

    2014-01-01

    Co-infections with parasites or viruses drive tuberculosis dynamics in humans, but little is known about their effects in other non-human hosts. This work aims to investigate the relationship between Mycobacterium bovis infection and other pathogens in wild boar (Sus scrofa), a recognized reservoir of bovine tuberculosis (bTB) in Mediterranean ecosystems. For this purpose, it has been assessed whether contacts with common concomitant pathogens are associated with the development of severe bTB lesions in 165 wild boar from mid-western Spain. The presence of bTB lesions affecting only one anatomic location (cervical lymph nodes), or more severe patterns affecting more than one location (mainly cervical lymph nodes and lungs), was assessed in infected animals. In addition, the existence of contacts with other pathogens such as porcine circovirus type 2 (PCV2), Aujeszky's disease virus (ADV), swine influenza virus, porcine reproductive and respiratory syndrome virus, Mycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae, Haemophilus parasuis and Metastrongylus spp, was evaluated by means of serological, microbiological and parasitological techniques. The existence of contacts with a structured community of pathogens in wild boar infected by M. bovis was statistically investigated by null models. Association between this community of pathogens and bTB severity was examined using a Partial Least Squares regression approach. Results showed that adult wild boar infected by M. bovis had contacted with some specific, non-random pathogen combinations. Contact with PCV2, ADV and infection by Metastrongylus spp, was positively correlated to tuberculosis severity. Therefore, measures against these concomitant pathogens such as vaccination or deworming, might be useful in tuberculosis control programmes in the wild boar. However, given the unexpected consequences of altering any community of organisms, further research should evaluate the impact of such measures under

  2. 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

  3. From cholera to corals: Viruses as drivers of virulence in a major coral bacterial pathogen

    PubMed Central

    Weynberg, Karen D.; Voolstra, Christian R.; Neave, Matthew J.; Buerger, Patrick; van Oppen, Madeleine J. H.

    2015-01-01

    Disease is an increasing threat to reef-building corals. One of the few identified pathogens of coral disease is the bacterium Vibrio coralliilyticus. In Vibrio cholerae, infection by a bacterial virus (bacteriophage) results in the conversion of non-pathogenic strains to pathogenic strains and this can lead to cholera pandemics. Pathogenicity islands encoded in the V. cholerae genome play an important role in pathogenesis. Here we analyse five whole genome sequences of V. coralliilyticus to examine whether virulence is similarly driven by horizontally acquired elements. We demonstrate that bacteriophage genomes encoding toxin genes with homology to those found in pathogenic V. cholerae are integrated in V. coralliilyticus genomes. Virulence factors located on chromosomal pathogenicity islands also exist in some strains of V. coralliilyticus. The presence of these genetic signatures indicates virulence in V. coralliilyticus is driven by prophages and other horizontally acquired elements. Screening for pathogens of coral disease should target conserved regions in these elements. PMID:26644037

  4. Evolution of highly pathogenic avian influenza H5N1 viruses in Egypt indicating progressive adaptation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Highly pathogenic avian influenza (HPAI) virus of the H5N1 subtype was first diagnosed in poultry in Egypt in 2006, and since then the disease became enzootic in poultry throughout the country affecting the poultry industry and village poultry as well as infecting humans. Vaccination has been used ...

  5. Domestic pigs have low susceptibility to H5N1 highly pathogenic avian influenza viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background. Genetic reassortment of H5N1 highly pathogenic avian influenza viruses (HPAI) with currently circulating human influenza A strains is one possibility that could lead to efficient human-to-human transmissibility. Domestic pigs which are susceptible to infection with both human and avian ...

  6. Influenza virus respiratory infection and transmission following ocular inoculation in ferrets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    While influenza viruses are a common respiratory pathogen, sporadic reports of conjunctivitis following human infection demonstrates the ability of this virus to cause disease outside of the respiratory tract. The ocular surface represents both a potential site of virus replication and a portal of e...

  7. Capsid coding sequences of foot-and-mouth disease viruses are determinants of pathogenicity in pigs.

    PubMed

    Lohse, Louise; Jackson, Terry; Bøtner, Anette; Belsham, Graham J

    2012-05-24

    The surface exposed capsid proteins, VP1, VP2 and VP3, of foot-and-mouth disease virus (FMDV) determine its antigenicity and the ability of the virus to interact with host-cell receptors. Hence, modification of these structural proteins may alter the properties of the virus.In the present study we compared the pathogenicity of different FMDVs in young pigs. In total 32 pigs, 7-weeks-old, were exposed to virus, either by direct inoculation or through contact with inoculated pigs, using cell culture adapted (O1K B64), chimeric (O1K/A-TUR and O1K/O-UKG) or field strain (O-UKG/34/2001) viruses. The O1K B64 virus and the two chimeric viruses are identical to each other except for the capsid coding region.Animals exposed to O1K B64 did not exhibit signs of disease, while pigs exposed to each of the other viruses showed typical clinical signs of foot-and-mouth disease (FMD). All pigs infected with the O1K/O-UKG chimera or the field strain (O-UKG/34/2001) developed fulminant disease. Furthermore, 3 of 4 in-contact pigs exposed to the O1K/O-UKG virus died in the acute phase of infection, likely from myocardial infection. However, in the group exposed to the O1K/A-TUR chimeric virus, only 1 pig showed symptoms of disease within the time frame of the experiment (10 days). All pigs that developed clinical disease showed a high level of viral RNA in serum and infected pigs that survived the acute phase of infection developed a serotype specific antibody response. It is concluded that the capsid coding sequences are determinants of FMDV pathogenicity in pigs.

  8. Grapevine Pathogenic Microorganisms: Understanding Infection Strategies and Host Response Scenarios

    PubMed Central

    Armijo, Grace; Schlechter, Rudolf; Agurto, Mario; Muñoz, Daniela; Nuñez, Constanza; Arce-Johnson, Patricio

    2016-01-01

    Grapevine (Vitis vinifera L.) is one of the most important fruit crop worldwide. Commercial cultivars are greatly affected by a large number of pathogenic microorganisms that cause diseases during pre- and/or post-harvest periods, affecting production, processing and export, along with fruit quality. Among the potential threats, we can find bacteria, fungi, oomycete, or viruses with different life cycles, infection mechanisms and evasion strategies. While plant–pathogen interactions are cycles of resistance and susceptibility, resistance traits from natural resources are selected and may be used for breeding purposes and for a sustainable agriculture. In this context, here we summarize some of the most important diseases affecting V. vinifera together with their causal agents. The aim of this work is to bring a comprehensive review of the infection strategies deployed by significant types of pathogens while understanding the host response in both resistance and susceptibility scenarios. New approaches being used to uncover grapevine status during biotic stresses and scientific-based procedures needed to control plant diseases and crop protection are also addressed. PMID:27066032

  9. Partial heterologous protection by low pathogenic H9N2 virus against natural H9N2-PB1 gene reassortant highly pathogenic H5N1 virus in chickens.

    PubMed

    Dash, Sandeep Kumar; Kumar, Manoj; Kataria, Jag Mohan; Nagarajan, Shanmugasundaram; Tosh, Chakradhar; Murugkar, Harshad V; Kulkarni, Diwakar D

    2016-06-01

    Low pathogenic avian influenza H9N2 and highly pathogenic avian influenza H5N1 viruses continue to co-circulate in chickens. Prior infection with low pathogenic avian influenza can modulate the outcome of H5N1 infection. In India, low pathogenic H9N2 and highly pathogenic H5N1 avian influenza viruses are co-circulating in poultry. Herein, by using chickens with prior infection of A/chicken/India/04TI05/2012 (H9N2) virus we explored the outcome of infection with H5N1 virus A/turkey/India/10CA03/2012 natural PB1 gene reassortant from H9N2. Four groups (E1-E4) of SPF chickens (n = 6) prior inoculated with 10(6) EID50 of H9N2 virus were challenged with 10(6) EID50 of H5N1 natural reassortant (PB1-H9N2) virus at days 1 (group E1); 3 (group E2); 7 (group E3) and 14 (group E4) post H9N2 inoculation. The survival percentage in groups E1-E4 was 0, 100, 66.6 and 50%, respectively. Virus shedding periods for groups E1-E4 were 3, 4, 7 and 9 days, respectively post H5N1 challenge. Birds of group E1 and E2 were shedding both H9N2 and H5N1 viruses and mean viral RNA copy number was higher in oropharyngeal swabs than cloacal swabs. In group, E3 and E4 birds excreted only H5N1 virus and mean viral RNA copy number was higher in most cloacal swabs than oral swabs. These results indicate that prior infection with H9N2 virus could protect from lethal challenge of reassortant H5N1 virus as early as with three days prior H9N2 inoculation and protection decreased in groups E3 and E4 as time elapsed. However, prior infection with H9N2 did not prevent infection with H5N1 virus and birds continue to excrete virus in oropharyngeal and cloacal swabs. Amino acid substitution K368E was found in HA gene of excreted H5N1 virus of group E3. Hence, concurrent infection can also cause emergence of viruses with mutations leading to virus evolution. The results of this study are important for the surveillance and epidemiological data analysis where both H9N2 and H5N1 viruses are co-circulating.

  10. Centrality in the host–pathogen interactome is associated with pathogen fitness during infection

    PubMed Central

    Crua Asensio, Núria; Muñoz Giner, Elisabet; de Groot, Natalia Sánchez; Torrent Burgas, Marc

    2017-01-01

    To perform their functions proteins must interact with each other, but how these interactions influence bacterial infection remains elusive. Here we demonstrate that connectivity in the host–pathogen interactome is directly related to pathogen fitness during infection. Using Y. pestis as a model organism, we show that the centrality-lethality rule holds for pathogen fitness during infection but only when the host–pathogen interactome is considered. Our results suggest that the importance of pathogen proteins during infection is directly related to their number of interactions with the host. We also show that pathogen proteins causing an extensive rewiring of the host interactome have a higher impact in pathogen fitness during infection. Hence, we conclude that hubs in the host–pathogen interactome should be explored as promising targets for antimicrobial drug design. PMID:28090086

  11. Centrality in the host-pathogen interactome is associated with pathogen fitness during infection

    NASA Astrophysics Data System (ADS)

    Crua Asensio, Núria; Muñoz Giner, Elisabet; de Groot, Natalia Sánchez; Torrent Burgas, Marc

    2017-01-01

    To perform their functions proteins must interact with each other, but how these interactions influence bacterial infection remains elusive. Here we demonstrate that connectivity in the host-pathogen interactome is directly related to pathogen fitness during infection. Using Y. pestis as a model organism, we show that the centrality-lethality rule holds for pathogen fitness during infection but only when the host-pathogen interactome is considered. Our results suggest that the importance of pathogen proteins during infection is directly related to their number of interactions with the host. We also show that pathogen proteins causing an extensive rewiring of the host interactome have a higher impact in pathogen fitness during infection. Hence, we conclude that hubs in the host-pathogen interactome should be explored as promising targets for antimicrobial drug design.

  12. High-pathogenicity avian influenza virus in the reproductive tract of chickens.

    PubMed

    Sá e Silva, M; Rissi, D R; Pantin-Jackwood, M; Swayne, D E

    2013-11-01

    Infection with high-pathogenicity avian influenza virus (HPAIV) has been associated with a wide range of clinical manifestations in poultry, including severe depression in egg production and isolation of HPAIV from eggs laid by infected hens. To evaluate the pathobiology in the reproductive tract of chickens, adult hens were inoculated intranasally with 3 HPAIV strains. All 3 strains induced lesions in the reproductive tract 36 to 72 hours after inoculation. Positive immunostaining was observed in all segments of the reproductive tract, occurring predominantly in stromal cells and superficial germinal epithelium of the ovary, in mucosal epithelial cells and less often glandular epithelium throughout the oviduct, and in vascular endothelium. This study generates important data and explains previously reported virus isolation from yolk, due to ovarian virus replication, and virus recovery from albumin, due to virus replication in epithelial cells in several segments of the oviduct.

  13. 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.

  14. Zika virus and the never-ending story of emerging pathogens and transfusion medicine.

    PubMed

    Marano, Giuseppe; Pupella, Simonetta; Vaglio, Stefania; Liumbruno, Giancarlo M; Grazzini, Giuliano

    2016-03-01

    In the last few years, the transfusion medicine community has been paying special attention to emerging vector-borne diseases transmitted by arboviruses. Zika virus is the latest of these pathogens and is responsible for major outbreaks in Africa, Asia and, more recently, in previously infection-naïve territories of the Pacific area. Many issues regarding this emerging pathogen remain unclear and require further investigation. National health authorities have adopted different prevention strategies. The aim of this review article is to discuss the currently available, though limited, information and the potential impact of this virus on transfusion medicine.

  15. Genesis and Dissemination of Highly Pathogenic H5N6 Avian Influenza Viruses.

    PubMed

    Yang, Lei; Zhu, Wenfei; Li, Xiaodan; Bo, Hong; Zhang, Ye; Zou, Shumei; Gao, Rongbao; Dong, Jie; Zhao, Xiang; Chen, Wenbing; Dong, Libo; Zou, Xiaohui; Xing, Yongcai; Wang, Dayan; Shu, Yuelong

    2017-03-01

    Clade 2.3.4.4 highly pathogenic avian influenza viruses (H5Nx) have spread from Asia to other parts of the world. Since 2014, human infections with clade 2.3.4.4 highly pathogenic avian influenza H5N6 viruses have been continuously reported in China. To investigate the genesis of the virus, we analyzed 123 H5 or N6 environmental viruses sampled from live-poultry markets or farms from 2012 to 2015 in Mainland China. Our results indicated that clade 2.3.4.4 H5N2/N6/N8 viruses shared the same hemagglutinin gene as originated in early 2009. From 2012 to 2015, the genesis of highly pathogenic avian influenza H5N6 viruses occurred via two independent pathways. Three major reassortant H5N6 viruses (reassortants A, B, and C) were generated. Internal genes of reassortant A and B viruses and reassortant C viruses derived from clade 2.3.2.1c H5N1 and H9N2 viruses, respectively. Many mammalian adaption mutations and antigenic variations were detected among the three reassortant viruses. Considering their wide circulation and dynamic reassortment in poultry, we highly recommend close monitoring of the viruses in poultry and humans. IMPORTANCE Since 2014, clade 2.3.4.4 highly pathogenic avian influenza (H5Nx) viruses have caused many outbreaks in both wild and domestic birds globally. Severe human cases with novel H5N6 viruses in this group were also reported in China in 2014 and 2015. To investigate the genesis of the genetic diversity of these H5N6 viruses, we sequenced 123 H5 or N6 environmental viruses sampled from 2012 to 2015 in China. Sequence analysis indicated that three major reassortants of these H5N6 viruses had been generated by two independent evolutionary pathways. The H5N6 reassortant viruses had been detected in most provinces of southern China and neighboring countries. Considering the mammalian adaption mutations and antigenic variation detected, the spread of these viruses should be monitored carefully due to their pandemic potential.

  16. Can Plant Viruses Cross the Kingdom Border and Be Pathogenic to Humans?

    PubMed Central

    Balique, Fanny; Lecoq, Hervé; Raoult, Didier; Colson, Philippe

    2015-01-01

    Phytoviruses are highly prevalent in plants worldwide, including vegetables and fruits. Humans, and more generally animals, are exposed daily to these viruses, among which several are extremely stable. It is currently accepted that a strict separation exists between plant and vertebrate viruses regarding their host range and pathogenicity, and plant viruses are believed to infect only plants. Accordingly, plant viruses are not considered to present potential pathogenicity to humans and other vertebrates. Notwithstanding these beliefs, there are many examples where phytoviruses circulate and propagate in insect vectors. Several issues are raised here that question if plant viruses might further cross the kingdom barrier to cause diseases in humans. Indeed, there is close relatedness between some plant and animal viruses, and almost identical gene repertoires. Moreover, plant viruses can be detected in non-human mammals and humans samples, and there are evidence of immune responses to plant viruses in invertebrates, non-human vertebrates and humans, and of the entry of plant viruses or their genomes into non-human mammal cells and bodies after experimental exposure. Overall, the question raised here is unresolved, and several data prompt the additional extensive study of the interactions between phytoviruses and non-human mammals and humans, and the potential of these viruses to cause diseases in humans. PMID:25903834

  17. Can plant viruses cross the kingdom border and be pathogenic to humans?

    PubMed

    Balique, Fanny; Lecoq, Hervé; Raoult, Didier; Colson, Philippe

    2015-04-20

    Phytoviruses are highly prevalent in plants worldwide, including vegetables and fruits. Humans, and more generally animals, are exposed daily to these viruses, among which several are extremely stable. It is currently accepted that a strict separation exists between plant and vertebrate viruses regarding their host range and pathogenicity, and plant viruses are believed to infect only plants. Accordingly, plant viruses are not considered to present potential pathogenicity to humans and other vertebrates. Notwithstanding these beliefs, there are many examples where phytoviruses circulate and propagate in insect vectors. Several issues are raised here that question if plant viruses might further cross the kingdom barrier to cause diseases in humans. Indeed, there is close relatedness between some plant and animal viruses, and almost identical gene repertoires. Moreover, plant viruses can be detected in non-human mammals and humans samples, and there are evidence of immune responses to plant viruses in invertebrates, non-human vertebrates and humans, and of the entry of plant viruses or their genomes into non-human mammal cells and bodies after experimental exposure. Overall, the question raised here is unresolved, and several data prompt the additional extensive study of the interactions between phytoviruses and non-human mammals and humans, and the potential of these viruses to cause diseases in humans.

  18. 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.

  19. 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

  20. Pathobiological features of a novel, highly pathogenic avian influenza A(H5N8) virus.

    PubMed

    Kim, Young-Il; Pascua, Philippe Noriel Q; Kwon, Hyeok-Il; Lim, Gyo-Jin; Kim, Eun-Ha; Yoon, Sun-Woo; Park, Su-Jin; Kim, Se Mi; Choi, Eun-Ji; Si, Young-Jae; Lee, Ok-Jun; Shim, Woo-Sub; Kim, Si-Wook; Mo, In-Pil; Bae, Yeonji; Lim, Yong Taik; Sung, Moon Hee; Kim, Chul-Joong; Webby, Richard J; Webster, Robert G; Choi, Young Ki

    2014-10-01

    The endemicity of highly pathogenic avian influenza (HPAI) A(H5N1) viruses in Asia has led to the generation of reassortant H5 strains with novel gene constellations. A newly emerged HPAI A(H5N8) virus caused poultry outbreaks in the Republic of Korea in 2014. Because newly emerging high-pathogenicity H5 viruses continue to pose public health risks, it is imperative that their pathobiological properties be examined. Here, we characterized A/mallard duck/Korea/W452/2014 (MDk/W452(H5N8)), a representative virus, and evaluated its pathogenic and pandemic potential in various animal models. We found that MDk/W452(H5N8), which originated from the reassortment of wild bird viruses harbored by migratory waterfowl in eastern China, replicated systemically and was lethal in chickens, but appeared to be attenuated, albeit efficiently transmitted, in ducks. Despite predominant attachment to avian-like virus receptors, MDk/W452(H5N8) also exhibited detectable human virus-like receptor binding and replicated in human respiratory tract tissues. In mice, MDk/W452(H5N8) was moderately pathogenic and had limited tissue tropism relative to previous HPAI A(H5N1) viruses. It also induced moderate nasal wash titers in inoculated ferrets; additionally, it was recovered in extrapulmonary tissues and one of three direct-contact ferrets seroconverted without shedding. Moreover, domesticated cats appeared to be more susceptible than dogs to virus infection. With their potential to become established in ducks, continued circulation of A(H5N8) viruses could alter the genetic evolution of pre-existing avian poultry strains. Overall, detailed virological investigation remains a necessity given the capacity of H5 viruses to evolve to cause human illness with few changes in the viral genome.

  1. Risk reduction modeling of high pathogenicity avian influenza virus titers in non-pasteurized liquid egg obtained from infected but undetected chicken flocks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Control of highly pathogenic avian influenza (HPAI) has traditionally involved the establishment of disease containment zones, where poultry products are only permitted to move from within a containment area under permit. Non-pasteurized liquid egg (NPLE) is one such commodity for which movements ma...

  2. 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.

  3. [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

  4. An experimental study of the pathogenicity of a duck hepatitis A virus genotype C isolate in specific pathogen free ducklings.

    PubMed

    Zhang, Huanrong; Pi, JinKui; Tang, Cheng; Yue, Hua; Yang, Falong

    2012-12-01

    Duck hepatitis A virus genotype C (DHAV-C), recognized recently, is one of the pathogens causing fatal duck viral hepatitis in ducklings, especially in Asia. To demonstrate the pathogenesis of the DHAV-C isolate, 3-day-old specific pathogen free ducklings were inoculated subcutaneously with a DHAV-C isolate and the clinical signs were observed. Virus distribution, histological and apoptotic morphological changes of various tissues were examined at different times post inoculation. The serial, characteristic changes included haemorrhage and swelling of the liver. Apoptotic cells and virus antigen staining were found in all of the tissues examined. Where more virus antigen staining was detected, there were more severe histopathological and apoptotic changes. The amount of virus antigen and the histological and apoptotic morphological changes agreed with each other and became increasingly severe with length of time after infection. Apoptotic cells were ubiquitously distributed, especially among lymphocytes, macrophages and monocytes in immune organs such as the bursa of Fabricius, thymus and spleen, and in liver, kidney and cerebral cells. Necrosis was also observed within 72 h post inoculation in all organs examined, except the cerebrum, and was characterized by cell swelling and collapsed plasma membrane. These results suggest that the recent outbreak of disease caused by DHAV-C virus is pantropic, causing apoptosis and necrosis of different organs. The apoptosis and necrosis caused by the DHAV-C field strain in this study is associated with pathogenesis and DHAV-C-induced lesions.

  5. Analysis by single-gene reassortment demonstrates that the 1918 influenza virus is functionally compatible with a low-pathogenicity avian influenza virus in mice.

    PubMed

    Qi, Li; Davis, A Sally; Jagger, Brett W; Schwartzman, Louis M; Dunham, Eleca J; Kash, John C; Taubenberger, Jeffery K

    2012-09-01

    The 1918-1919 "Spanish" influenza pandemic is estimated to have caused 50 million deaths worldwide. Understanding the origin, virulence, and pathogenic properties of past pandemic influenza viruses, including the 1918 virus, is crucial for current public health preparedness and future pandemic planning. The origin of the 1918 pandemic virus has not been resolved, but its coding sequences are very like those of avian influenza virus. The proteins encoded by the 1918 virus differ from typical low-pathogenicity avian influenza viruses at only a small number of amino acids in each open reading frame. In this study, a series of chimeric 1918 influenza viruses were created in which each of the eight 1918 pandemic virus gene segments was replaced individually with the corresponding gene segment of a prototypical low-pathogenicity avian influenza (LPAI) H1N1 virus in order to investigate functional compatibility of the 1918 virus genome with gene segments from an LPAI virus and to identify gene segments and mutations important for mammalian adaptation. This set of eight "7:1" chimeric viruses was compared to the parental 1918 and LPAI H1N1 viruses in intranasally infected mice. Seven of the 1918 LPAI 7:1 chimeric viruses replicated and caused disease equivalent to the fully reconstructed 1918 virus. Only the chimeric 1918 virus containing the avian influenza PB2 gene segment was attenuated in mice. This attenuation could be corrected by the single E627K amino acid change, further confirming the importance of this change in mammalian adaptation and mouse pathogenicity. While the mechanisms of influenza virus host switch, and particularly mammalian host adaptation are still only partly understood, these data suggest that the 1918 virus, whatever its origin, is very similar to avian influenza virus.

  6. Comparative pathogenicity of four strains of Aleutian disease virus for pastel and sapphire mink.

    PubMed Central

    Hadlow, W J; Race, R E; Kennedy, R C

    1983-01-01

    Information was sought on the comparative pathogenicity of four North American strains (isolates) of Aleutian disease virus for royal pastel (a non-Aleutian genotype) and sapphire (an Aleutian genotype) mink. The four strains (Utah-1, Ontario [Canada], Montana, and Pullman [Washington]), all of mink origin, were inoculated intraperitoneally and intranasally in serial 10-fold dilutions. As indicated by the appearance of specific antibody (counterimmunoelectrophoresis test), all strains readily infected both color phases of mink, and all strains were equally pathogenic for sapphire mink. Not all strains, however, regularly caused Aleutian disease in pastel mink. Infection of pastel mink with the Utah-1 strain invariably led to fatal disease. Infection with the Ontario strain caused fatal disease nearly as often. The Pullman strain, by contrast, almost never caused disease in infected pastel mink. The pathogenicity of the Montana strain for this color phase was between these extremes. These findings emphasize the need to distinguish between infection and disease when mink are exposed to Aleutian disease virus. The distinction has important implications for understanding the natural history of Aleutian disease virus infection in ranch mink. PMID:6193063

  7. 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.

  8. Parasites can enhance infections of fish with bacterial pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In aquaculture systems, fish are commonly infected by multiple pathogens, including parasites. Parasite Ichthyophthirius multifiliis (Ich) and bacterium Edwardsiella ictaluri are two common pathogens of cultured channel catfish. The objectives were to 1) evaluate the susceptibility of Ich parasitize...

  9. Avian influenza virus isolates from wild birds replicate and cause disease in a mouse model of infection.

    PubMed

    Driskell, Elizabeth A; Jones, Cheryl A; Stallknecht, David E; Howerth, Elizabeth W; Tompkins, S Mark

    2010-04-10

    The direct transmission of highly pathogenic avian influenza (HPAI) viruses to humans in Eurasia and subsequent disease has sparked research efforts leading to better understanding of HPAI virus transmission and pathogenicity in mammals. There has been minimal focus on examining the capacity of circulating low pathogenic wild bird avian influenza viruses to infect mammals. We have utilized a mouse model for influenza virus infection to examine 28 North American wild bird avian influenza virus isolates that include the hemagglutinin subtypes H2, H3, H4, H6, H7, and H11. We demonstrate that many wild bird avian influenza viruses of several different hemagglutinin types replicate in this mouse model without adaptation and induce histopathologic lesions similar to other influenza virus infections but cause minimal morbidity. These findings demonstrate the potential of wild avian influenza viruses to directly infect mice without prior adaptation and support their potential role in emergence of pandemic influenza.

  10. [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.

  11. A mouse model for testing the pathogenicity of equine herpes virus-1 strains.

    PubMed

    van Woensel, P A; Goovaerts, D; Markx, D; Visser, N

    1995-07-01

    A mouse model was developed for testing the pathogenicity of equine herpes virus-1 (EHV-1) strains. The model was validated with EHV-1 strains that are known to be of a low or high pathogenicity in horses. From all parameters tested, the safety index, which was calculated from the body weights of the mice after infection, proved to be the best predictive parameter. When this parameter was used, good and reliable correlations were found with the pathogenicity of the EHV-1 strains in horses. This method enabled the differentiation between the two experimental EHV-1 strains whose genetic backgrounds were supposedly equal.

  12. Pathogenicity of different rabies virus isolates and protection test in vaccinated mice.

    PubMed

    Cunha, Elenice M S; Nassar, Alessandra F C; Lara, Maria do Carmo C S H; Villalobos, Eliana C M; Sato, Go; Kobayashi, Yuki; Shoji, Youko; Itou, Takuya; Sakai, Takeo; Ito, Fumio H

    2010-01-01

    This study was aimed to evaluate and compare the pathogenicity of rabies virus isolated from bats and dogs, and to verify the efficacy of a commercial rabies vaccine against these isolates. For evaluation of pathogenicity, mice were inoculated by the intramuscular route (IM) with 500MICLD₅₀/0.03 mL of the viruses. The cross-protection test was performed by vaccinating groups of mice by the subcutaneous route and challenged through the intracerebral (IC) route. Isolates were fully pathogenic when inoculated by the IC route. When inoculated intramuscularly, the pathogenicity observed showed different death rates: 60.0% for the Desmodus rotundus isolate; 50.0% for dog and Nyctinomops laticaudatus isolates; 40.0% for Artibeus lituratus isolate; 9.5% Molossus molossus isolate; and 5.2% for the Eptesicus furinalis isolate. Mice receiving two doses of the vaccine and challenged by the IC route with the isolates were fully protected. Mice receiving only one dose of vaccine were partially protected against the dog isolate. The isolates from bats were pathogenic by the IC route in mice. However, when inoculated through the intramuscular route, the same isolates were found with different degrees of pathogenicity. The results of this work suggest that a commercial vaccine protects mice from infection with bat rabies virus isolates, in addition to a canine rabies virus isolate.

  13. Cellular and humoral mediated immunity and distribution of viral antigen in chickens after infection with a low pathogenic avian influenza virus (H4N6) isolated from wild ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Four-week-old commercial chickens were intranasally inoculated with an H4N6 low pathogenicity avian influenza virus (LPAIV) isolated from a duck in Ukraine. Cecum, spleen, lung, and trachea samples were collected from birds from 1 to 21 days post inoculation (dpi) and examined by immunohistochemica...

  14. Higher plant diversity promotes higher diversity of fungal pathogens, while it decreases pathogen infection per plant.

    PubMed

    Rottstock, Tanja; Joshi, Jasmin; Kummer, Volker; Fischer, Markus

    2014-07-01

    Fungal plant pathogens are common in natural communities where they affect plant physiology, plant survival, and biomass production. Conversely, pathogen transmission and infection may be regulated by plant community characteristics such as plant species diversity and functional composition that favor pathogen diversity through increases in host diversity while simultaneously reducing pathogen infection via increased variability in host density and spatial heterogeneity. Therefore, a comprehensive understanding of multi-host multi-pathogen interactions is of high significance in the context of biodiversity-ecosystem functioning. We investigated the relationship between plant diversity and aboveground obligate parasitic fungal pathogen ("pathogens" hereafter) diversity and infection in grasslands of a long-term, large-scale, biodiversity experiment with varying plant species (1-60 species) and plant functional group diversity (1-4 groups). To estimate pathogen infection of the plant communities, we visually assessed pathogen-group presence (i.e., rusts, powdery mildews, downy mildews, smuts, and leaf-spot diseases) and overall infection levels (combining incidence and severity of each pathogen group) in 82 experimental plots on all aboveground organs of all plant species per plot during four surveys in 2006. Pathogen diversity, assessed as the cumulative number of pathogen groups on all plant species per plot, increased log-linearly with plant species diversity. However, pathogen incidence and severity, and hence overall infection, decreased with increasing plant species diversity. In addition, co-infection of plant individuals by two or more pathogen groups was less likely with increasing plant community diversity. We conclude that plant community diversity promotes pathogen-community diversity while at the same time reducing pathogen infection levels of plant individuals.

  15. Looking at protists as a source of pathogenic viruses.

    PubMed

    La Scola, Bernard

    2014-12-01

    In the environment, protozoa are predators of bacteria and feed on them. The possibility that some protozoa could be a source of human pathogens is consistent with the discovery that free-living amoebae were the reservoir of Legionella pneumophila, the agent of Legionnaires' disease. Later, while searching for Legionella in the environment using amoeba co-culture, the first giant virus, Acanthamoeba polyphaga mimivirus, was discovered. Since then, many other giant viruses have been isolated, including Marseilleviridae, Pithovirus sibericum, Cafeteria roenbergensis virus and Pandoravirus spp. The methods used to isolate all of these viruses are herein reviewed. By analogy to Legionella, it was originally suspected that these viruses could be human pathogens. After showing by indirect evidence, such as sero-epidemiologic studies, that it was possible for these viruses to be human pathogens, the recent isolation of some of these viruses (belonging to the Mimiviridae and Marseilleviridae families) in humans in the context of pathologic conditions shows that they are opportunistic human pathogens in some instances.

  16. 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

  17. Experimental biology and pathogenesis of Junin virus infection in animals and man*

    PubMed Central

    Weissenbacher, M. C.; De Guerrero, L. B.; Boxaca, M. C.

    1975-01-01

    A fatal disease resembling Argentine haemorrhagic fever of man has been produced in guinea-pigs and mice by inoculation with Junin virus. Infected guinea-pigs show macroscopic and microscopic haemorrhagic lesions, marked bone marrow changes, decreased leukocytes and platelets in the peripheral blood, and impairment of immunological response. This response permits differentiation between pathogenic (XJ) and attenuated (XJ Cl3) strains. Guinea-pigs inoculated with the XJ Cl3 strain develop an inapparent infection accompanied by slight haematological changes, the appearance of antibody, and protection against challenge with the pathogenic strain. The attenuated strain has been used successfully as an immunizing antigen in 636 human volunteers. Guinea-pigs infected with Tacaribe virus show cross-protection against Junin virus, with the presence of heterologous neutralizing antibodies. Suckling mice infected with Junin virus develop a typical viral encephalitis; the pathogenicity of the virus decreases with increasing age of the mice. Experiments with thymectomized mice and with mice treated with antithymocyte serum suggest that the pathogenicity of Junin virus in this host is related to the integrity of the thymus-dependent immune system. There is evidence that humoral antibodies do not play any role in the development of the encephalitic lesions but rather protect mice against Junin virus infection. A recent serological survey among laboratory workers and inhabitants of the endemic area has demonstrated the presence of inapparent infection with Junin virus. PMID:182401

  18. Orsay, Santeuil and Le Blanc viruses primarily infect intestinal cells in Caenorhabditis nematodes.

    PubMed

    Franz, Carl J; Renshaw, Hilary; Frezal, Lise; Jiang, Yanfang; Félix, Marie-Anne; Wang, David

    2014-01-05

    The discoveries of Orsay, Santeuil and Le Blanc viruses, three viruses infecting either Caenorhabditis elegans or its relative Caenorhabditis briggsae, enable the study of virus-host interactions using natural pathogens of these two well-established model organisms. We characterized the tissue tropism of infection in Caenorhabditis nematodes by these viruses. Using immunofluorescence assays targeting proteins from each of the viruses, and in situ hybridization, we demonstrate viral proteins and RNAs localize to intestinal cells in larval stage Caenorhabditis nematodes. Viral proteins were detected in one to six of the 20 intestinal cells present in Caenorhabditis nematodes. In Orsay virus-infected C. elegans, viral proteins were detected as early as 6h post-infection. The RNA-dependent RNA polymerase and capsid proteins of Orsay virus exhibited different subcellular localization patterns. Collectively, these observations provide the first experimental insights into viral protein expression in any nematode host, and broaden our understanding of viral infection in Caenorhabditis nematodes.

  19. The role of C5a in acute lung injury induced by highly pathogenic viral infections

    PubMed Central

    Wang, Renxi; Xiao, He; Guo, Renfeng; Li, Yan; Shen, Beifen

    2015-01-01

    The complement system, an important part of innate immunity, plays a critical role in pathogen clearance. Unregulated complement activation is likely to play a crucial role in the pathogenesis of acute lung injury (ALI) induced by highly pathogenic virus including influenza A viruses H5N1, H7N9, and severe acute respiratory syndrome (SARS) coronavirus. In highly pathogenic virus-induced acute lung diseases, high levels of chemotactic and anaphylatoxic C5a were produced as a result of excessive complement activaiton. Overproduced C5a displays powerful biological activities in activation of phagocytic cells, generation of oxidants, and inflammatory sequelae named “cytokine storm”, and so on. Blockade of C5a signaling have been implicated in the treatment of ALI induced by highly pathogenic virus. Herein, we review the literature that links C5a and ALI, and review our understanding of the mechanisms by which C5a affects ALI during highly pathogenic viral infection. In particular, we discuss the potential of the blockade of C5a signaling to treat ALI induced by highly pathogenic viruses. PMID:26060601

  20. New evidence that Deformed Wing Virus and Black Queen Cell Virus are Multi-host pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The host-range breadth of pathogens can have important consequences for pathogens’ long term evolution and virulence, and play critical roles in the emergence and spread of the new diseases. Black queen cell virus (BQCV) and Deformed wing virus (DWV) are the two most common and prevalent viruses in...

  1. Protection against Influenza Virus Infection of Mice Fed Bifidobacterium breve YIT4064

    PubMed Central

    Yasui, Hisako; Kiyoshima, Junko; Hori, Tetuji; Shida, Kan

    1999-01-01

    Mice fed Bifidobacterium breve YIT4064 and immunized orally with influenza virus were more strongly protected against influenza virus infection of the lower respiratory tract than ones immunized with influenza virus only. The number of mice with enhanced anti-influenza virus immunoglobulin G (IgG) in serum upon oral administration of B. breve YIT4064 and oral immunization with influenza virus was significantly greater than that upon oral immunization with influenza virus only. These findings demonstrated that the oral administration of B. breve YIT4064 increased anti-influenza virus IgG antibodies in serum and protected against influenza virus infection. The oral administration of B. breve YIT4064 may enhance antigen-specific IgG against various pathogenic antigens taken orally and induce protection against various virus infections. PMID:10066652

  2. Two Genetically Similar H9N2 Influenza A Viruses Show Different Pathogenicity in Mice

    PubMed Central

    Liu, Qingtao; Liu, Yuzhuo; Yang, Jing; Huang, Xinmei; Han, Kaikai; Zhao, Dongmin; Bi, Keran; Li, Yin

    2016-01-01

    H9N2 Avian influenza virus has repeatedly infected humans and other mammals, which highlights the need to determine the pathogenicity and the corresponding mechanism of this virus for mammals. In this study, we found two H9N2 viruses with similar genetic background but with different pathogenicity in mice. The A/duck/Nanjing/06/2003 (NJ06) virus was highly pathogenic for mice, with a 50% mouse lethal dose (MLD50) of 102.83 50% egg infectious dose (EID50), whereas the A/duck/Nanjing/01/1999 (NJ01) virus was low pathogenic for mice, with a MLD50 of >106.81 EID50. Further studies showed that the NJ06 virus grew faster and reached significantly higher titers than NJ01 in vivo and in vitro. Moreover, the NJ06 virus induced more severe lung lesions, and higher levels of inflammatory cellular infiltration and cytokine response in lungs than NJ01 did. However, only 12 different amino acid residues (HA-K157E, NA-A9T, NA-R435K, PB2-T149P, PB2-K627E, PB1-R187K, PA-L548M, PA-M550L, NP-G127E, NP-P277H, NP-D340N, NS1-D171N) were found between the two viruses, and all these residues except for NA-R435K were located in the known functional regions involved in interaction of viral proteins or between the virus and host factors. Summary, our results suggest that multiple amino acid differences may be responsible for the higher pathogenicity of the NJ06 virus for mice, resulting in lethal infection, enhanced viral replication, severe lung lesions, and excessive inflammatory cellular infiltration and cytokine response in lungs. These observations will be helpful for better understanding the pathogenic potential and the corresponding molecular basis of H9N2 viruses that might pose threats to human health in the future. PMID:27867373

  3. Viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lytic bacteriophages, viruses which infect and lyse bacterial cells, can provide a natural method to reduce bacterial pathogens on produce commodities. The use of multi-phage cocktails is most likely to be effective against bacterial pathogens on produce commodities, and minimize the development of...

  4. Enteric pathogens associated with gastrointestinal dysfunction in children with HIV infection.

    PubMed

    Ramos-Soriano, A G; Saavedra, J M; Wu, T C; Livingston, R A; Henderson, R A; Perman, J A; Yolken, R H

    1996-04-01

    Infants and young children with HIV infection commonly suffer from gastrointestinal manifestations of their disease. Many HIV infected children have evidence of persistent diarrhoea, malabsorption, malnutrition or growth failure. The aetiology and pathogenesis of gastrointestinal dysfunction in HIV infected children have not been well defined. We performed immunocytochemical analyses on intestinal tissue from 19 HIV-infected children with gastrointestinal dysfunction or growth failure. None of these 19 children had microbial pathogens identified in faecal samples using standard microbiological methods. Intestinal tissues were obtained from the children by biopsy and were examined for antigens from Pneumocystis carinii, cytomegalovirus (CMV) and herpes simplex virus (HSV) using the avidin-biotin-complex immunohistochemical technique and monoclonal or monospecific antibodies. We detected at least one of these pathogens in samples from eight (42%) of 19 HIV infected children. P. carinii was the most prevalent pathogen, found in five of the eight HIV infected children. All of the children with intestinal pneumocystis infection were receiving prophylaxis directed at the prevention of pulmonary disease with this organism and none of them were undergoing active pulmonary infection. We also identified CMV antigens in intestinal tissues from four children and HSV antigens in intestinal tissues from one child. Two children were infected with more than one pathogen. On the other hand, none of these pathogens were found in the tissues obtained from 10 HIV-uninfected patients who had intestinal tissues obtained for chronic non-infectious diarrheal and inflammatory diseases (P < 0.01, Fisher's exact test). Our findings indicate that some children with HIV infection and gastrointestinal dysfunction may be infected with opportunistic pathogens despite negative analyses employing standard microbiological methods. Our study also indicates that HIV infected children can undergo

  5. Influenza A Virus Acquires Enhanced Pathogenicity and Transmissibility after Serial Passages in Swine

    PubMed Central

    Wei, Kai; Sun, Honglei; Sun, Zhenhong; Sun, Yipeng; Kong, Weili; Pu, Juan; Ma, Guangpeng; Yin, Yanbo; Yang, Hanchun; Guo, Xin; Chang, Kin-Chow

    2014-01-01

    ABSTRACT Genetic and phylogenetic analyses suggest that the pandemic H1N1/2009 virus was derived from well-established swine influenza lineages; however, there is no convincing evidence that the pandemic virus was generated from a direct precursor in pigs. Furthermore, the evolutionary dynamics of influenza virus in pigs have not been well documented. Here, we subjected a recombinant virus (rH1N1) with the same constellation makeup as the pandemic H1N1/2009 virus to nine serial passages in pigs. The severity of infection sequentially increased with each passage. Deep sequencing of viral quasispecies from the ninth passage found five consensus amino acid mutations: PB1 A469T, PA 1129T, NA N329D, NS1 N205K, and NEP T48N. Mutations in the hemagglutinin (HA) protein, however, differed greatly between the upper and lower respiratory tracts. Three representative viral clones with the five consensus mutations were selected for functional evaluation. Relative to the parental virus, the three viral clones showed enhanced replication and polymerase activity in vitro and enhanced replication, pathogenicity, and transmissibility in pigs, guinea pigs, and ferrets in vivo. Specifically, two mutants of rH1N1 (PB1 A469T and a combination of NS1 N205K and NEP T48N) were identified as determinants of transmissibility in guinea pigs. Crucially, one mutant viral clone with the five consensus mutations, which also carried D187E, K211E, and S289N mutations in its HA, additionally was able to infect ferrets by airborne transmission as effectively as the pandemic virus. Our findings demonstrate that influenza virus can acquire viral characteristics that are similar to those of the pandemic virus after limited serial passages in pigs. IMPORTANCE We demonstrate here that an engineered reassortant swine influenza virus, with the same gene constellation pattern as the pandemic H1N1/2009 virus and subjected to only nine serial passages in pigs, acquired greatly enhanced virulence and

  6. Influenza A virus acquires enhanced pathogenicity and transmissibility after serial passages in swine.

    PubMed

    Wei, Kai; Sun, Honglei; Sun, Zhenhong; Sun, Yipeng; Kong, Weili; Pu, Juan; Ma, Guangpeng; Yin, Yanbo; Yang, Hanchun; Guo, Xin; Chang, Kin-Chow; Liu, Jinhua

    2014-10-01

    Genetic and phylogenetic analyses suggest that the pandemic H1N1/2009 virus was derived from well-established swine influenza lineages; however, there is no convincing evidence that the pandemic virus was generated from a direct precursor in pigs. Furthermore, the evolutionary dynamics of influenza virus in pigs have not been well documented. Here, we subjected a recombinant virus (rH1N1) with the same constellation makeup as the pandemic H1N1/2009 virus to nine serial passages in pigs. The severity of infection sequentially increased with each passage. Deep sequencing of viral quasispecies from the ninth passage found five consensus amino acid mutations: PB1 A469T, PA 1129T, NA N329D, NS1 N205K, and NEP T48N. Mutations in the hemagglutinin (HA) protein, however, differed greatly between the upper and lower respiratory tracts. Three representative viral clones with the five consensus mutations were selected for functional evaluation. Relative to the parental virus, the three viral clones showed enhanced replication and polymerase activity in vitro and enhanced replication, pathogenicity, and transmissibility in pigs, guinea pigs, and ferrets in vivo. Specifically, two mutants of rH1N1 (PB1 A469T and a combination of NS1 N205K and NEP T48N) were identified as determinants of transmissibility in guinea pigs. Crucially, one mutant viral clone with the five consensus mutations, which also carried D187E, K211E, and S289N mutations in its HA, additionally was able to infect ferrets by airborne transmission as effectively as the pandemic virus. Our findings demonstrate that influenza virus can acquire viral characteristics that are similar to those of the pandemic virus after limited serial passages in pigs. Importance: We demonstrate here that an engineered reassortant swine influenza virus, with the same gene constellation pattern as the pandemic H1N1/2009 virus and subjected to only nine serial passages in pigs, acquired greatly enhanced virulence and transmissibility

  7. 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

  8. 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.

  9. The Synthetic Antiviral Drug Arbidol Inhibits Globally Prevalent Pathogenic Viruses

    PubMed Central

    Pécheur, Eve-Isabelle; Borisevich, Viktoriya; Halfmann, Peter; Morrey, John D.; Smee, Donald F.; Prichard, Mark; Mire, Chad E.; Kawaoka, Yoshihiro; Geisbert, Thomas W.

    2016-01-01

    ABSTRACT Arbidol (ARB) is a synthetic antiviral originally developed to combat influenza viruses. ARB is currently used clinically in several countries but not in North America. We have previously shown that ARB inhibits in vitro hepatitis C virus (HCV) by blocking HCV entry and replication. In this report, we expand the list of viruses that are inhibited by ARB and demonstrate that ARB suppresses in vitro infection of mammalian cells with Ebola virus (EBOV), Tacaribe arenavirus, and human herpesvirus 8 (HHV-8). We also confirm suppression of hepatitis B virus and poliovirus by ARB. ARB inhibited EBOV Zaire Kikwit infection when added before or at the same time as virus infection and was less effective when added 24 h after EBOV infection. Experiments with recombinant vesicular stomatitis virus (VSV) expressing the EBOV Zaire glycoprotein showed that infection was inhibited by ARB at early stages, most likely at the level of viral entry into host cells. ARB inhibited HHV-8 replication to a similar degree as cidofovir. Our data broaden the spectrum of antiviral efficacy of ARB to include globally prevalent viruses that cause significant morbidity and mortality. IMPORTANCE There are many globally prevalent viruses for which there are no licensed vaccines or antiviral medicines. Some of these viruses, such as Ebola virus or members of the arenavirus family, rapidly cause severe hemorrhagic diseases that can be fatal. Other viruses, such as hepatitis B virus or human herpesvirus 8 (HHV-8), establish persistent infections that cause chronic illnesses, including cancer. Thus, finding an affordable, effective, and safe drug that blocks many viruses remains an unmet medical need. The antiviral drug arbidol (ARB), already in clinical use in several countries as an anti-influenza treatment, has been previously shown to suppress the growth of many viruses. In this report, we expand the list of viruses that are blocked by ARB in a laboratory setting to include Ebola virus

  10. Changes in population dynamics in mutualistic versus pathogenic viruses.

    PubMed

    Roossinck, Marilyn J

    2011-01-01

    Although generally regarded as pathogens, viruses can also be mutualists. A number of examples of extreme mutualism (i.e., symbiogenesis) have been well studied. Other examples of mutualism are less common, but this is likely because viruses have rarely been thought of as having any beneficial effects on their hosts. The effect of mutualism on the population dynamics of viruses is a topic that has not been addressed experimentally. However, the potential for understanding mutualism and how a virus might become a mutualist may be elucidated by understanding these dynamics.

  11. 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...

  12. Chikungunya virus: recent advances in epidemiology, host pathogen interaction and vaccine strategies.

    PubMed

    Deeba, Farah; Islam, Asimul; Kazim, Syed Naqui; Naqvi, Irshad Hussain; Broor, Shobha; Ahmed, Anwar; Parveen, Shama

    2016-04-01

    The Chikungunya virus is a re-emerging alphavirus that belongs to the family Togaviridae. The symptoms include fever, rashes, nausea and joint pain that may last for months. The laboratory diagnosis of the infection is based on the serologic assays, virus isolation and molecular methods. The pathogenesis of the Chikungunya viral infection is not completely understood. Some of the recent investigations have provided information on replication of the virus in various cells and organs. In addition, some recent reports have indicated that the severity of the disease is correlated with the viral load and cytokines. The Chikungunya virus infection re-emerged as an explosive epidemic during 2004-09 affecting millions of people in the Indian Ocean. Subsequent global attention was given to research on this viral pathogen due to its broad area of geographical distribution during this epidemic. Chikungunya viral infection has become a challenge for the public health system because of the absence of a vaccine as well as antiviral drugs. A number of potential vaccine candidates have been tested on humans and animal models during clinical and preclinical trials. In this review, we mainly discuss the host-pathogen relationship, epidemiology and recent advances in the development of drugs and vaccines for the Chikungunya viral infection.

  13. 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.

  14. 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.

  15. A silkworm model of pathogenic bacterial infection.

    PubMed

    Kaito, C; Sekimizu, K

    2007-10-01

    Silkworms are invertebrate animals that are killed by bacteria pathogenic against humans, such as Staphylococcus aureus, Streptococcus pyogenes, Pseudomonas aeruginosa, and Vibrio cholerae. Injection into the hemolymph of antibiotics that are clinically used for human patients abolishes the killing effects. There are several advantages to using silkworms as an infection model, such as low cost, the absence of ethical problems that are associated with the use of mammals, and a body size large enough to handle while injecting sample solution into the hemolymph. We screened S. aureus mutants with attenuated virulence against silkworms and found three novel virulence regulatory genes, cvfA, cvfB, and cvfC. These genes contribute to virulence against mice and are required for exotoxin production. The cvfA gene is required for expression of the agr locus, which regulates most exotoxin genes, and a novel DNA binding protein SarZ. Silkworms are susceptible to S. aureus beta toxin, P. aeruginosa exotoxin A, and diphtheria toxin. Therefore, silkworms are a promising infection model animal for the identification and evaluation of virulenceassociated genes.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. Susceptibility of primary chicken intestinal epithelial cells for low pathogenic avian influenza virus and velogenic viscerotropic Newcastle disease virus.

    PubMed

    Kaiser, Annette; Willer, Thomas; Sid, Hicham; Petersen, Henning; Baumgärtner, Wolfgang; Steinberg, Pablo; Rautenschlein, Silke

    2016-10-02

    Avian influenza virus (AIV) and Newcastle disease virus (NDV) share a high tropism for the avian respiratory epithelium and may cause severe clinical disease associated with high mortality. Both viruses have different pathotypes, which may lead to differences in the severity of the disease. Respiratory epithelial cells were shown to be the primary target cells for infection and replication. Nevertheless, intestinal epithelial cells (IECs) were also suggested as target cells for both viruses in avian species. Most studies on AIV and NDV focused on the respiratory tract, while information regarding the virus-host interaction at the intestinal epithelial cell interface is lacking. We established a primary chicken IEC culture model. Primary chicken embryo fibroblast cultures (CEFs) were used for comparison. IECs and CEFs were infected with a low infectious dose (LID; multiplicity of infection, MOI, of 0.01) or high infectious dose (HID, MOI of 1), of low pathogenic AIV (LPAIV) H9N2 or velogenic viscerotropic NDV (vvNDV) Herts 33/56. Virus replication, mRNA expression pattern of the type I and type III interferon (IFN) and related genes IFIT5 (interferon-induced protein with tetratricopeptide repeats 5) and ISG12 (interferon stimulated gene 12) were investigated at four, 16, and 24h post infection (hpi). The results suggest high susceptibility of primary chicken IECs for these AIV and NDV strains. Replication rates and expression pattern of IFNs as well as related genes differed between the infecting viruses as well as cell culture systems. Both viruses induced an IFN λ-increase of more than 30-fold in IECs, while IFN-α and IFN-β mRNA expression was either downregulated or only slightly increased with up to 10fold changes for the latter at 24h post LPAIV-infection. These results suggest a possible role of IFN λ in the control of viruses at the gut epithelial surface. LPAIV induced upregulation of IFIT5 as well as ISG12 expression in a dose and time dependent manner

  3. Innate immune response to arenaviral infection: a focus on the highly pathogenic New World hemorrhagic arenaviruses

    PubMed Central

    Koma, Takaaki; Huang, Cheng; Kolokoltsova, Olga A; Brasier, Allan R; Paessler, Slobodan

    2013-01-01

    Arenaviruses are enveloped, negative-stranded RNA viruses that belong to the family Arenaviridae. This diverse family can be further classified into OW (Old World) and NW (New World) arenaviruses based on their antigenicity, phylogeny, and geographical distribution. Many of the NW arenaviruses are highly pathogenic viruses that cause systemic human infections characterized by hemorrhagic fever and/or neurological manifestations, constituting public health problems in their endemic regions. NW arenavirus infection induces a variety of host innate immune responses, which could contribute to the viral pathogenesis and/or influence the final outcome of virus infection in vitro as well as in vivo. On the other hand, NW arenaviruses have also developed several strategies to counteract the host innate immune response. We will review current knowledge regarding the interplay between the host innate immune response and NW arenavirus infection in vitro and in vivo, with emphasis on viral-encoded proteins and their effect on the type I interferon response. PMID:24075870

  4. Innate immune response to arenaviral infection: a focus on the highly pathogenic New World hemorrhagic arenaviruses.

    PubMed

    Koma, Takaaki; Huang, Cheng; Kolokoltsova, Olga A; Brasier, Allan R; Paessler, Slobodan

    2013-12-13

    Arenaviruses are enveloped, negative-stranded RNA viruses that belong to the family Arenaviridae. This diverse family can be further classified into OW (Old World) and NW (New World) arenaviruses based on their antigenicity, phylogeny, and geographical distribution. Many of the NW arenaviruses are highly pathogenic viruses that cause systemic human infections characterized by hemorrhagic fever and/or neurological manifestations, constituting public health problems in their endemic regions. NW arenavirus infection induces a variety of host innate immune responses, which could contribute to the viral pathogenesis and/or influence the final outcome of virus infection in vitro and in vivo. On the other hand, NW arenaviruses have also developed several strategies to counteract the host innate immune response. We will review current knowledge regarding the interplay between the host innate immune response and NW arenavirus infection in vitro and in vivo, with emphasis on viral-encoded proteins and their effect on the type I interferon response.

  5. Utilization of C-C chemokine receptor 5 by the envelope glycoproteins of a pathogenic simian immunodeficiency virus, SIVmac239.

    PubMed Central

    Marcon, L; Choe, H; Martin, K A; Farzan, M; Ponath, P D; Wu, L; Newman, W; Gerard, N; Gerard, C; Sodroski, J

    1997-01-01

    We examined chemokine receptors for the ability to facilitate the infection of CD4-expressing cells by viruses containing the envelope glycoproteins of a pathogenic simian immunodeficiency virus, SIVmac239. Expression of either human or simian C-C chemokine receptor CCR5 allowed the SIVmac239 envelope glycoproteins to mediate virus entry and cell-to-cell fusion. Thus, distantly related immunodeficiency viruses such as SIV and the primary human immunodeficiency virus type 1 isolates can utilize CCR5 as an entry cofactor. PMID:9032394

  6. Cell autonomous regulation of herpes and influenza virus infection by the circadian clock

    PubMed Central

    Edgar, Rachel S.; Stangherlin, Alessandra; Nagy, Andras D.; Nicoll, Michael P.; Efstathiou, Stacey; O’Neill, John S.; Reddy, Akhilesh B.

    2016-01-01

    Viruses are intracellular pathogens that hijack host cell machinery and resources to replicate. Rather than being constant, host physiology is rhythmic, undergoing circadian (∼24 h) oscillations in many virus-relevant pathways, but whether daily rhythms impact on viral replication is unknown. We find that the time of day of host infection regulates virus progression in live mice and individual cells. Furthermore, we demonstrate that herpes and influenza A virus infections are enhanced when host circadian rhythms are abolished by disrupting the key clock gene transcription factor Bmal1. Intracellular trafficking, biosynthetic processes, protein synthesis, and chromatin assembly all contribute to circadian regulation of virus infection. Moreover, herpesviruses differentially target components of the molecular circadian clockwork. Our work demonstrates that viruses exploit the clockwork for their own gain and that the clock represents a novel target for modulating viral replication that extends beyond any single family of these ubiquitous pathogens. PMID:27528682

  7. Pathogens Penetrating the Central Nervous System: Infection Pathways and the Cellular and Molecular Mechanisms of Invasion

    PubMed Central

    Dando, Samantha J.; Mackay-Sim, Alan; Norton, Robert; Currie, Bart J.; St. John, James A.; Ekberg, Jenny A. K.; Batzloff, Michael

    2014-01-01

    SUMMARY The brain is well protected against microbial invasion by cellular barriers, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). In addition, cells within the central nervous system (CNS) are capable of producing an immune response against invading pathogens. Nonetheless, a range of pathogenic microbes make their way to the CNS, and the resulting infections can cause significant morbidity and mortality. Bacteria, amoebae, fungi, and viruses are capable of CNS invasion, with the latter using axonal transport as a common route of infection. In this review, we compare the mechanisms by which bacterial pathogens reach the CNS and infect the brain. In particular, we focus on recent data regarding mechanisms of bacterial translocation from the nasal mucosa to the brain, which represents a little explored pathway of bacterial invasion but has been proposed as being particularly important in explaining how infection with Burkholderia pseudomallei can result in melioidosis encephalomyelitis. PMID:25278572

  8. 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.

  9. Papaya Ringspot Virus: Characteristics, Pathogenicity, Sequence Variability and Control

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Taxonomy: Papaya ringspot virus (PRSV) is an aphid-transmitted plant virus belonging to the genus Potyvirus of the family Potyviridae with a positive sense RNA genome. PRSV isolates belong to either one of two major strains, P-type or W-type. The P-type infects both papaya and cucurbits whereas th...

  10. Natural and experimental infection of Caenorhabditis nematodes by novel viruses related to nodaviruses.

    PubMed

    Félix, Marie-Anne; Ashe, Alyson; Piffaretti, Joséphine; Wu, Guang; Nuez, Isabelle; Bélicard, Tony; Jiang, Yanfang; Zhao, Guoyan; Franz, Carl J; Goldstein, Leonard D; Sanroman, Mabel; Miska, Eric A; Wang, David

    2011-01-25

    An ideal model system to study antiviral immunity and host-pathogen co-evolution would combine a genetically tractable small animal with a virus capable of naturally infecting the host organism. The use of C. elegans as a model to define host-viral interactions has been limited by the lack of viruses known to infect nematodes. From wild isolates of C. elegans and C. briggsae with unusual morphological phenotypes in intestinal cells, we identified two novel RNA viruses distantly related to known nodaviruses, one infecting specifically C. elegans (Orsay virus), the other C. briggsae (Santeuil virus). Bleaching of embryos cured infected cultures demonstrating that the viruses are neither stably integrated in the host genome nor transmitted vertically. 0.2 µm filtrates of the infected cultures could infect cured animals. Infected animals continuously maintained viral infection for 6 mo (∼50 generations), demonstrating that natural cycles of horizontal virus transmission were faithfully recapitulated in laboratory culture. In addition to infecting the natural C. elegans isolate, Orsay virus readily infected laboratory C. elegans mutants defective in RNAi and yielded higher levels of viral RNA and infection symptoms as compared to infection of the corresponding wild-type N2 strain. These results demonstrated a clear role for RNAi in the defense against this virus. Furthermore, different wild C. elegans isolates displayed differential susceptibility to infection by Orsay virus, thereby affording genetic approaches to defining antiviral loci. This discovery establishes a bona fide viral infection system to explore the natural ecology of nematodes, host-pathogen co-evolution, the evolution of small RNA responses, and innate antiviral mechanisms.

  11. Natural and Experimental Infection of Caenorhabditis Nematodes by Novel Viruses Related to Nodaviruses

    PubMed Central

    Wu, Guang; Nuez, Isabelle; Bélicard, Tony; Jiang, Yanfang; Zhao, Guoyan; Franz, Carl J.; Goldstein, Leonard D.; Sanroman, Mabel; Miska, Eric A.; Wang, David

    2011-01-01

    An ideal model system to study antiviral immunity and host-pathogen co-evolution would combine a genetically tractable small animal with a virus capable of naturally infecting the host organism. The use of C. elegans as a model to define host-viral interactions has been limited by the lack of viruses known to infect nematodes. From wild isolates of C. elegans and C. briggsae with unusual morphological phenotypes in intestinal cells, we identified two novel RNA viruses distantly related to known nodaviruses, one infecting specifically C. elegans (Orsay virus), the other C. briggsae (Santeuil virus). Bleaching of embryos cured infected cultures demonstrating that the viruses are neither stably integrated in the host genome nor transmitted vertically. 0.2 µm filtrates of the infected cultures could infect cured animals. Infected animals continuously maintained viral infection for 6 mo (∼50 generations), demonstrating that natural cycles of horizontal virus transmission were faithfully recapitulated in laboratory culture. In addition to infecting the natural C. elegans isolate, Orsay virus readily infected laboratory C. elegans mutants defective in RNAi and yielded higher levels of viral RNA and infection symptoms as compared to infection of the corresponding wild-type N2 strain. These results demonstrated a clear role for RNAi in the defense against this virus. Furthermore, different wild C. elegans isolates displayed differential susceptibility to infection by Orsay virus, thereby affording genetic approaches to defining antiviral loci. This discovery establishes a bona fide viral infection system to explore the natural ecology of nematodes, host-pathogen co-evolution, the evolution of small RNA responses, and innate antiviral mechanisms. PMID:21283608

  12. 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.

  13. 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

  14. Characterization of the H5N1 highly pathogenic avian influenza virus derived from wild pikas in China.

    PubMed

    Zhou, Jiyong; Sun, Wenbo; Wang, Junhua; Guo, Junqing; Yin, Wei; Wu, Nanping; Li, Lanjuan; Yan, Yan; Liao, Ming; Huang, Yu; Luo, Kaijian; Jiang, Xuetao; Chen, Hualan

    2009-09-01

    The highly pathogenic H5N1 avian influenza virus emerged from China in 1996 and has spread across Eurasia and Africa, with a continuous stream of new cases of human infection appearing since the first large-scale outbreak among migratory birds at Qinghai Lake. The role of wild birds, which are the natural reservoirs for the virus, in the epidemiology of the H5N1 virus has raised great public health concern, but their role in the spread of the virus within the natural ecosystem of free-ranging terrestrial wild mammals remains unclear. In this study, we investigated H5N1 virus infection in wild pikas in an attempt to trace the circulation of the virus. Seroepidemiological surveys confirmed a natural H5N1 virus infection of wild pikas in their native environment. The hemagglutination gene of the H5N1 virus isolated from pikas reveals two distinct evolutionary clades, a mixed/Vietnam H5N1 virus sublineage (MV-like pika virus) and a wild bird Qinghai (QH)-like H5N1 virus sublineage (QH-like pika virus). The amino acid residue (glutamic acid) at position 627 encoded by the PB2 gene of the MV-like pika virus was different from that of the QH-like pika virus; the residue of the MV-like pika virus was the same as that of the goose H5N1 virus (A/GS/Guangdong [GD]/1/96). Further, we discovered that in contrast to the MV-like pika virus, which is nonpathogenic to mice, the QH-like pika virus is highly pathogenic. To mimic the virus infection of pikas, we intranasally inoculated rabbits, a species closely related to pikas, with the H5N1 virus of pika origin. Our findings first demonstrate that wild pikas are mammalian hosts exposed to H5N1 subtype avian influenza viruses in the natural ecosystem and also imply a potential transmission of highly pathogenic avian influenza virus from wild mammals into domestic mammalian hosts and humans.

  15. The New World arenavirus Tacaribe virus induces caspase-dependent apoptosis in infected cells.

    PubMed

    Wolff, Svenja; Groseth, Allison; Meyer, Bjoern; Jackson, David; Strecker, Thomas; Kaufmann, Andreas; Becker, Stephan

    2016-04-01

    The Arenaviridae is a diverse and growing family of viruses that already includes more than 25 distinct species. While some of these viruses have a significant impact on public health, others appear to be non-pathogenic. At present little is known about the host cell responses to infection with different arenaviruses, particularly those found in the New World; however, apoptosis is known to play an important role in controlling infection of many viruses. Here we show that infection with Tacaribe virus (TCRV), which is widely considered the prototype for non-pathogenic arenaviruses, leads to stronger induction of apoptosis than does infection with its human-pathogenic relative Junín virus. TCRV-induced apoptosis occurred in several cell types during late stages of infection and was shown to be caspase-dependent, involving the activation of caspases 3, 7, 8 and 9. Further, UV-inactivated TCRV did not induce apoptosis, indicating that the activation of this process is dependent on active viral replication/transcription. Interestingly, when apoptosis was inhibited, growth of TCRV was not enhanced, indicating that apoptosis does not have a direct negative effect on TCRV infection in vitro. Taken together, our data identify and characterize an important virus-host cell interaction of the prototypic, non-pathogenic arenavirus TCRV, which provides important insight into the growing field of arenavirus research aimed at better understanding the diversity in responses to different arenavirus infections and their functional consequences.

  16. 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

  17. 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…

  18. 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.

  19. Why is co-infection with influenza virus and bacteria so difficult to control?

    PubMed Central

    Cauley, Linda S.; Vella, Anthony T.

    2015-01-01

    Influenza viruses are genetically labile pathogens which avoid immune detection by constantly changing their coat proteins. Most human infections are caused by mildly pathogenic viruses which rarely cause life-threatening disease in healthy people, but some individuals with a weakened immune system can experience severe complications. Widespread infections with highly pathogenic strains of influenza virus are less common, but have the potential to cause enormous death tolls among healthy adults if infection rates reach pandemic proportions. Increased virulence has been attributed to a variety of factors, including enhanced susceptibility to co-infection with common strains of bacteria. The mechanisms that facilitate dual infection are a major focus of current research, as preventative measures are needed to avert future pandemics PMID:25636959

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. Characterization of duck H5N1 influenza viruses with differing pathogenicity in mallard (Anas platyrhynchos) ducks.

    PubMed

    Tang, Yinghua; Wu, Peipei; Peng, Daxin; Wang, Xiaobo; Wan, Hongquan; Zhang, Pinghu; Long, Jinxue; Zhang, Wenjun; Li, Yanfang; Wang, Wenbin; Zhang, Xiaorong; Liu, Xiufan

    2009-12-01

    A number of H5N1 influenza outbreaks have occurred in aquatic birds in Asia. As aquatic birds are the natural reservoir of influenza A viruses and do not usually show clinical disease upon infection, the repeated H5N1 outbreaks have highlighted the importance of continuous surveillance on H5N1 viruses in aquatic birds. In the present study we characterized the biological properties of four H5N1 avian influenza viruses, which had been isolated from ducks, in different animal models. In specific pathogen free (SPF) chickens, all four isolates were highly pathogenic. In SPF mice, the S and Y isolates were moderately pathogenic. However, in mallard ducks, two isolates had low pathogenicity, while the other two were highly pathogenic and caused lethal infection. A representative isolate with high pathogenicity in ducks caused systemic infection and replicated effectively in all 10 organs tested in challenged ducks, whereas a representative isolate with low pathogenicity in ducks was only detected in some organs in a few challenged ducks. Comparison of complete genomic sequences from the four isolates showed that the same amino acid residues that have been reported to be associated with virulence and host adaption/restriction of influenza viruses were present in the PB2, HA, NA, M and NS genes, while the amino acid residues at the HA cleavage site were diverse. From these results it appeared that the virulence of H5N1 avian influenza viruses was increased for ducks and that amino acid substitutions at the HA cleavage site might have contributed to the differing pathogenicity of these isolates in mallards. A procedure for the intravenous pathogenicity index test in a mallard model for assessing the virulence of H5/H7 subtype avian influenza viruses in waterfowl is described.

  5. 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

  6. 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.

  7. 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

  8. 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

  9. Visual inspections of nursery stock fail to protect new plantings from Blueberry scorch virus infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Blueberry scorch virus (BlScV) is one of the most pervasive pathogens of highbush blueberry. The virus is aphid-vectored and exhibits a latent period between infection and symptom expression of up to 4 years. In many cases, we have observed BlScV symptom expression in new fields that is inconsistent...

  10. The Genus Aeromonas: Taxonomy, Pathogenicity, and Infection

    PubMed Central

    Janda, J. Michael; Abbott, Sharon L.

    2010-01-01

    Summary: Over the past decade, the genus Aeromonas has undergone a number of significant changes of practical importance to clinical microbiologists and scientists alike. In parallel with the molecular revolution in microbiology, several new species have been identified on a phylogenetic basis, and the genome of the type species, A. hydrophila ATCC 7966, has been sequenced. In addition to established disease associations, Aeromonas has been shown to be a significant cause of infections associated with natural disasters (hurricanes, tsunamis, and earthquakes) and has been linked to emerging or new illnesses, including near-drowning events, prostatitis, and hemolytic-uremic syndrome. Despite these achievements, issues still remain regarding the role that Aeromonas plays in bacterial gastroenteritis, the extent to which species identification should be attempted in the clinical laboratory, and laboratory reporting of test results from contaminated body sites containing aeromonads. This article provides an extensive review of these topics, in addition to others, such as taxonomic issues, microbial pathogenicity, and antimicrobial resistance markers. PMID:20065325

  11. Natural killer cell dysfunction during acute infection with foot-and-mouth diseaase virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Natural killer cells (NK) provide one of the initial barriers of cellular host defense against pathogens, in particular intracellular pathogens. The role of these cells in foot-and-mouth disease virus (FMDV) infection is unknown. Previously, we characterized the phenotype and function of NK cells fr...

  12. 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

  13. Viruses of Spiroplasma citri and their possible effects on pathogenicity.

    PubMed Central

    Townsend, R.

    1983-01-01

    Strains of Spiroplasma citri are persistently infected by viruses which have been separated into three groups on the basis of their morphology. The properties of each group are reviewed. Viruses normally only appear in spiroplasma cultures but recently all three types of particle have been identified in cells of a single strain of S. citri within an infected plant. Replication of a short-tailed polyhedral virus SP-V3 (ai) appears to be correlated with unusually mild symptom expression. Introduction of the virus with its host into plants already infected with a severe and potentially lethal strain of S. citri results in a marked suppression of symptoms and a reduction in the number of spiroplasmas. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 FIG. 6 PMID:6382829

  14. Pathogenic characteristics of persistent feline enteric coronavirus infection in cats.

    PubMed

    Vogel, Liesbeth; Van der Lubben, Mariken; te Lintelo, Eddie G; Bekker, Cornelis P J; Geerts, Tamara; Schuijff, Leontine S; Grinwis, Guy C M; Egberink, Herman F; Rottier, Peter J M

    2010-01-01

    Feline coronaviruses (FCoV) comprise two biotypes: feline enteric coronaviruses (FECV) and feline infectious peritonitis viruses (FIPV). FECV is associated with asymptomatic persistent enteric infections, while FIPV causes feline infectious peritonitis (FIP), a usually fatal systemic disease in domestic cats and some wild Felidae. FIPV arises from FECV by mutation. FCoV also occur in two serotypes, I and II, of which the serotype I viruses are by far the most prevalent in the field. Yet, most of our knowledge about FCoV infections relates to serotype II viruses, particularly about the FIPV, mainly because type I viruses grow poorly in cell culture. Hence, the aim of the present work was the detailed study of the epidemiologically most relevant viruses, the avirulent serotype I viruses. Kittens were inoculated oronasally with different doses of two independent FECV field strains, UCD and RM. Persistent infection could be reproducibly established. The patterns of clinical symptoms, faecal virus shedding and seroconversion were monitored for up to 10 weeks revealing subtle but reproducible differences between the two viruses. Faecal virus, i.e. genomic RNA, was detected during persistent FECV infection only in the large intestine, downstream of the appendix, and could occasionally be observed also in the blood. The implications of our results, particularly our insights into the persistently infected state, are discussed.

  15. Spontaneous substitutions in the vicinity of the V3 analog affect cell tropism and pathogenicity of simian immunodeficiency virus.

    PubMed Central

    Hirsch, V M; Martin, J E; Dapolito, G; Elkins, W R; London, W T; Goldstein, S; Johnson, P R

    1994-01-01

    Simian immunodeficiency virus (SIV) exists within tissues of infected macaques as a mixture of diverse genotypes. The goal of this study was to investigate the biologic significance of this variation in terms of cellular tropism and pathogenicity. PCR was used to amplify and clone 3'-half genomes from the spleen of an immunodeficiency SIV-infected pig-tailed macaque (Macaca nemestrina). Eight infectious clones were generated by ligation of respective 3' clones into a related SIVsm 5' clone, and virus stocks were generated by transient transfection. Four of these viruses were infectious for macaque peripheral blood mononuclear cells (PBMC) or monocyte-derived macrophages (MDM). Three viruses with distinct tropism for macaque PBMC or MDM were tested for in vivo infectivity and pathogenicity. The ability of these three viruses to infect PBMC and macrophages correlated with differences in infectivity and pathogenicity. Thus, a virus that was infectious for both PBMC and MDM was highly infectious for macaques and induced AIDS in half of the inoculated animals. In contrast, virus that was less infectious for PBMC and not infectious for MDM induced only transient viremia. Finally, a virus that was not infectious for either primary cell type did not infect macaques. Chimeric clones exchanging portions of the envelope gene of the 62A and smH4 molecular clones and a series of point mutants were used to map the determinant of tropism to a 60-amino-acid region of gp120 encompassing the V3 analog of SIV. Naturally occurring mutations within this region were critical for determining tropism and, as a result, pathogenicity of these SIVsm clones. Images PMID:8139042

  16. Influenza C virus infection in military recruits--symptoms and clinical manifestation.

    PubMed

    Kauppila, Jaana; Rönkkö, Esa; Juvonen, Raija; Saukkoriipi, Annika; Saikku, Pekka; Bloigu, Aini; Vainio, Olli; Ziegler, Thedi

    2014-05-01

    Due to the lack of rapid diagnostic tests, clinical features of Influenza C virus infections are poorly characterized. Respiratory infections in military recruits in eastern Finland were monitored between July 2004 and December 2005 in order to study the epidemiology and clinical picture of infections caused by this virus. Blood samples were obtained at entry and at the end of the military service, and during each episode of respiratory infection to measure antibody responses against 10 viral and 2 bacterial pathogens. If possible, sputum samples were collected during the acute phase of respiratory infection episodes. Symptoms of the episodes were recorded for comparison of the clinical picture caused by various infectious agents. Infection with influenza C virus was detected in 38 of 892 young men during their service. The virus usually caused a mild upper respiratory tract infection. Most typical clinical features of influenza C virus infection were cough, rhinitis, and hoarseness. A striking difference to infections caused by influenza A virus was the lack of fever. Influenza C virus is an important cause of a respiratory tract infection in army conscripts. Infections with this virus are usually mild but can be complicated in some cases.

  17. Pathogenic hantaviruses direct the adherence of quiescent platelets to infected endothelial cells.

    PubMed

    Gavrilovskaya, Irina N; Gorbunova, Elena E; Mackow, Erich R

    2010-05-01

    Hantavirus infections are noted for their ability to infect endothelial cells, cause acute thrombocytopenia, and trigger 2 vascular-permeability-based diseases. However, hantavirus infections are not lytic, and the mechanisms by which hantaviruses cause capillary permeability and thrombocytopenia are only partially understood. The role of beta(3) integrins in hemostasis and the inactivation of beta(3) integrin receptors by pathogenic hantaviruses suggest the involvement of hantaviruses in altered platelet and endothelial cell functions that regulate permeability. Here, we determined that pathogenic hantaviruses bind to quiescent platelets via a beta(3) integrin-dependent mechanism. This suggests that platelets may contribute to hantavirus dissemination within infected patients and provides a means by which hantavirus binding to beta(3) integrin receptors prevents platelet activation. The ability of hantaviruses to bind platelets further suggested that cell-associated hantaviruses might recruit platelets to the endothelial cell surface. Our findings indicate that Andes virus (ANDV)- or Hantaan virus (HTNV)-infected endothelial cells specifically direct the adherence of calcein-labeled platelets. In contrast, cells comparably infected with nonpathogenic Tula virus (TULV) failed to recruit platelets to the endothelial cell surface. Platelet adherence was dependent on endothelial cell beta(3) integrins and neutralized by the addition of the anti-beta(3) Fab fragment, c7E3, or specific ANDV- or HTNV-neutralizing antibodies. These findings indicate that pathogenic hantaviruses displayed on the surface of infected endothelial cells bind platelets and that a platelet layer covers the surface of infected endothelial cells. This fundamentally changes the appearance of endothelial cells and has the potential to alter cellular immune responses, platelet activation, and endothelial cell functions that affect vascular permeability. Hantavirus-directed platelet quiescence and

  18. 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

  19. 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.

  20. 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

  1. Presence of Pathogenic Bacteria and Viruses in the Daycare Environment.

    PubMed

    Ibfelt, Tobias; Engelund, Eva Hoy; Permin, Anders; Madsen, Jonas Stenløkke; Schultz, Anna Charlotte; Andersen, Leif Percival

    2015-10-01

    The number of children in daycare centers (DCCs) is rising. This increases exposure to microorganisms and infectious diseases. Little is known about which bacteria and viruses are present in the DCC environment and where they are located. In the study described in this article, the authors set out to determine the prevalence of pathogenic bacteria and viruses and to find the most contaminated fomites in DCCs. Fifteen locations in each DCC were sampled for bacteria, respiratory viruses, and gastrointestinal viruses. The locations were in the toilet, kitchen, and playroom areas and included nursery pillows, toys, and tables, among other things. Coliform bacteria were primarily found in the toilet and kitchen areas whereas nasopharyngeal bacteria were found mostly on toys and fabric surfaces in the playroom. Respiratory viruses were omnipresent in the DCC environment, especially on the toys.

  2. 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.

  3. Deletion of the meq gene significantly decreases immunosuppression in chickens caused by pathogenic marek's disease virus

    PubMed Central

    2011-01-01

    Background Marek's disease virus (MDV) causes an acute lymphoproliferative disease in chickens, resulting in immunosuppression, which is considered to be an integral aspect of the pathogenesis of Marek's disease (MD). A recent study showed that deletion of the Meq gene resulted in loss of transformation of T-cells in chickens and a Meq-null virus, rMd5ΔMeq, could provide protection superior to CVI988/Rispens. Results In the present study, to investigate whether the Meq-null virus could be a safe vaccine candidate, we constructed a Meq deletion strain, GX0101ΔMeq, by deleting both copies of the Meq gene from a pathogenic MDV, GX0101 strain, which was isolated in China. Pathogenesis experiments showed that the GX0101ΔMeq virus was fully attenuated in specific pathogen-free chickens because none of the infected chickens developed Marek's disease-associated lymphomas. The study also evaluated the effects of GX0101ΔMeq on the immune system in chickens after infection with GX0101ΔMeq virus. Immune system variables, including relative lymphoid organ weight, blood lymphocytes and antibody production following vaccination against AIV and NDV were used to assess the immune status of chickens. Experimental infection with GX0101ΔMeq showed that deletion of the Meq gene significantly decreased immunosuppression in chickens caused by pathogenic MDV. Conclusion These findings suggested that the Meq gene played an important role not only in tumor formation but also in inducing immunosuppressive effects in MDV-infected chickens. PMID:21205328

  4. Inactivation of pathogenic viruses by plant-derived tannins: strong effects of extracts from persimmon (Diospyros kaki) on a broad range of viruses.

    PubMed

    Ueda, Kyoko; Kawabata, Ryoko; Irie, Takashi; Nakai, Yoshiaki; Tohya, Yukinobu; Sakaguchi, Takemasa

    2013-01-01

    Tannins, plant-derived polyphenols and other related compounds, have been utilized for a long time in many fields such as the food industry and manufacturing. In this study, we investigated the anti-viral effects of tannins on 12 different viruses including both enveloped viruses (influenza virus H3N2, H5N3, herpes simplex virus-1, vesicular stomatitis virus, Sendai virus and Newcastle disease virus) and non-enveloped viruses (poliovirus, coxsachievirus, adenovirus, rotavirus, feline calicivirus and mouse norovirus). We found that extracts from persimmon (Diospyros kaki), which contains ca. 22% of persimmon tannin, reduced viral infectivity in more than 4-log scale against all of the viruses tested, showing strong anti-viral effects against a broad range of viruses. Other tannins derived from green tea, acacia and gallnuts were effective for some of the viruses, while the coffee extracts were not effective for any of the virus. We then investigated the mechanism of the anti-viral effects of persimmon extracts by using mainly influenza virus. Persimmon extracts were effective within 30 seconds at a concentration of 0.25% and inhibited attachment of the virus to cells. Pretreatment of cells with the persimmon extracts before virus infection or post-treatment after virus infection did not inhibit virus replication. Protein aggregation seems to be a fundamental mechanism underlying the anti-viral effect of persimmon tannin, since viral proteins formed aggregates when purified virions were treated with the persimmon extracts and since the anti-viral effect was competitively inhibited by a non-specific protein, bovine serum albumin. Considering that persimmon tannin is a food supplement, it has a potential to be utilized as a safe and highly effective anti-viral reagent against pathogenic viruses.

  5. 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

  6. Genetic characterization and pathogenicity assessment of highly pathogenic H5N1 avian influenza viruses isolated from migratory wild birds in 2011, South Korea.

    PubMed

    Kwon, Hyeok-Il; Song, Min-Suk; Pascua, Philippe Noriel Q; Baek, Yun Hee; Lee, Jun Han; Hong, Seung-Pyo; Rho, Jong-Bok; Kim, Jeong-Ki; Poo, Haryoung; Kim, Chul-Joong; Choi, Young Ki

    2011-09-01

    The continued spread of a highly pathogenic avian influenza (HPAI) H5N1 virus among wild birds and poultry has posed a potential threat to human public health. In the present study, we report the isolation of HPAI H5N1 viruses (A/Md/Korea/W401/11 and A/Md/Korea/W404/11) from fecal samples of migratory birds. Genetic and phlyogenetic analyses demonstrated that these viruses are genetically identical possessing gene segments from avian virus origin and showing highest sequence similarities (as high as 99.8%) to A/Ws/Hokkaido/4/11 and 2009-2010 Mongolian-like clade 2.3.2 isolates rather than previous Korean H5N1 viruses. Both viruses possess the polybasic motif (QRERRRK/R) in HA but other genes did not bear additional virulence markers. Pathogenicity of A/Md/Korea/W401/11 was assessed and compared with a 2006 clade 2.2 HPAI H5N1 migratory bird isolate (A/EM/Korea/W149/06) in chickens, ducks, mice and ferrets. Experimental infection in these hosts showed that both viruses have high pathogenic potential in chickens (2.3-3.0 LD(50)s) and mice (3.3-3.9 LD(50)s), but A/Md/Korea/W401/11 was less pathogenic in duck and ferret models. Despite recovery of both infection viruses in the upper respiratory tract, efficient ferret-to-ferret transmission was not observed. These data suggest that the 2011 Korean HPAI wild bird H5N1 virus could replicate in mammalian hosts without pre-adaptation but could not sustain subsequent infection. This study highlights the role of migratory birds in the perpetuation and spread of HPAI H5N1 viruses in Far-East Asia. With the changing pathobiology caused by H5N1 viruses among wild and poultry birds, continued surveillance of influenza viruses among migratory bird species remains crucial for effective monitoring of high-pathogenicity or pandemic influenza viruses.

  7. 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.

  8. 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%.

  9. 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.

  10. Serial infection of diverse host (Mus) genotypes rapidly impedes pathogen fitness and virulence

    PubMed Central

    Kubinak, Jason L.; Cornwall, Douglas H.; Hasenkrug, Kim J.; Adler, Frederick R.; Potts, Wayne K.

    2015-01-01

    Reduced genetic variation among hosts may favour the emergence of virulent infectious diseases by enhancing pathogen replication and its associated virulence due to adaptation to a limited set of host genotypes. Here, we test this hypothesis using experimental evolution of a mouse-specific retroviral pathogen, Friend virus (FV) complex. We demonstrate rapid fitness (i.e. viral titre) and virulence increases when FV complex serially infects a series of inbred mice representing the same genotype, but not when infecting a diverse array of inbred mouse strains modelling the diversity in natural host populations. Additionally, a single infection of a different host genotype was sufficient to constrain the emergence of a high fitness/high virulence FV complex phenotype in these experiments. The potent inhibition of viral fitness and virulence was associated with an observed loss of the defective retroviral genome (spleen focus-forming virus), whose presence exacerbates infection and drives disease in susceptible mice. Results from our experiments provide an important first step in understanding how genetic variation among vertebrate hosts influences pathogen evolution and suggests that serial exposure to different genotypes within a single host species may act as a constraint on pathogen adaptation that prohibits the emergence of more virulent infections. From a practical perspective, these results have implications for low-diversity host populations such as endangered species and domestic animals. PMID:25392466

  11. 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.

  12. Highly pathogenic avian influenza virus among wild birds in Mongolia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The central Asian country of Mongolia supports large populations of migratory water birds that migrate across much of Asia where highly pathogenic avian influenza (HPAI) virus subtype H5N1 is endemic. This, together with the near absence of domestic poultry, makes Mongolia an ideal location to unde...

  13. Rapidly expanding range of highly pathogenic avian influenza viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The recent introduction of highly pathogenic avian influenza virus (HPAIV) H5N8 into Europe and North America poses significant risks to poultry industries and wildlife populations and warrants continued and heightened vigilance. First discovered in South Korean poultry and wild birds in early 2014...

  14. In ovo and in vitro susceptibility of American alligators (Alligator mississippiensis) to avian influenza virus infection.

    PubMed

    Temple, Bradley L; Finger, John W; Jones, Cheryl A; Gabbard, Jon D; Jelesijevic, Tomislav; Uhl, Elizabeth W; Hogan, Robert J; Glenn, Travis C; Tompkins, S Mark

    2015-01-01

    Avian influenza has emerged as one of the most ubiquitous viruses within our biosphere. Wild aquatic birds are believed to be the primary reservoir of all influenza viruses; however, the spillover of H5N1 highly pathogenic avian influenza (HPAI) and the recent swine-origin pandemic H1N1 viruses have sparked increased interest in identifying and understanding which and how many species can be infected. Moreover, novel influenza virus sequences were recently isolated from New World bats. Crocodilians have a slow rate of molecular evolution and are the sister group to birds; thus they are a logical reptilian group to explore susceptibility to influenza virus infection and they provide a link between birds and mammals. A primary American alligator (Alligator mississippiensis) cell line, and embryos, were infected with four, low pathogenic avian influenza (LPAI) strains to assess susceptibility to infection. Embryonated alligator eggs supported virus replication, as evidenced by the influenza virus M gene and infectious virus detected in allantoic fluid and by virus antigen staining in embryo tissues. Primary alligator cells were also inoculated with the LPAI viruses and showed susceptibility based upon antigen staining; however, the requirement for trypsin to support replication in cell culture limited replication. To assess influenza virus replication in culture, primary alligator cells were inoculated with H1N1 human influenza or H5N1 HPAI viruses that replicate independent of trypsin. Both viruses replicated efficiently in culture, even at the 30 C temperature preferred by the alligator cells. This research demonstrates the ability of wild-type influenza viruses to infect and replicate within two crocodilian substrates and suggests the need for further research to assess crocodilians as a species potentially susceptible to influenza virus infection.

  15. Assessing microbial decontamination of indoor air with particular focus on human pathogenic viruses.

    PubMed

    Duchaine, Caroline

    2016-09-02

    Transmission of bacterial, fungal, and viral pathogens is of primary importance in public and occupational health and infection control. Although several standardized protocols have been proposed to target microbes on fomites through surface decontamination, use of microbicidal agents, and cleaning processes, only limited guidance is available on microbial decontamination of indoor air to reduce the risk of pathogen transmission between individuals. This article reviews the salient aspects of airborne transmission of infectious agents, exposure assessment, in vitro assessment of microbicidal agents, and processes for air decontamination for infection prevention and control. Laboratory-scale testing (eg, rotating chambers, wind tunnels) and promising field-scale methodologies to decontaminate indoor air are also presented. The potential of bacteriophages as potential surrogates for the study of airborne human pathogenic viruses is also discussed.

  16. Pathogenicity of an H5N1 highly pathogenic avian influenza virus isolated in the 2010-2011 winter in Japan to mandarin ducks.

    PubMed

    Soda, Kosuke; Usui, Tatsufumi; Uno, Yukiko; Yoneda, Kumiko; Yamaguchi, Tsuyoshi; Ito, Toshihiro

    2013-01-01

    Widespread outbreaks of highly pathogenic avian influenza (HPAI) caused by H5N1 viruses occurred in wild birds in Japan from 2010-2011. Forty out of 63 deceased wild birds belonged to the order Anseriformes, and mandarin duck was one of the dominant species. To estimate the risk of mandarin ducks as a source of virus infection in the environment, we examined the pathogenicity of a causal H5N1 HPAI virus to mandarin ducks. About half of the mandarin ducks died by inoculation with 10(7.0)TCID50 of A/mandarin duck/Miyazaki/22M807-1/2011 (H5N1). Viruses were mainly recovered from the trachea of the ducks sacrificed at three days post inoculation (d.p.i.). Viruses were recovered from the laryngopharyngeal swabs of the observation group until 5 d.p.i. In ducks that died at the late phase of infection, viruses were detected in the systemic organs, such as lung, kidney and colon. Together, these results showed that the H5N1 HPAI viruses, which belonged to clade 2.3.2.1 and are mainly circulating in East Asia, were lethal to mandarin ducks, indicating that mandarin ducks have the potential to disseminate the virus to other bird species. Therefore, wild birds should be kept out of poultry farms to prevent HPAI outbreaks in the future.

  17. Pathogenicity and transmissibility of reassortant H9 influenza viruses with genes from pandemic H1N1 virus.

    PubMed

    Qiao, Chuanling; Liu, Qinfang; Bawa, Bhupinder; Shen, Huigang; Qi, Wenbao; Chen, Ying; Mok, Chris Ka Pun; García-Sastre, Adolfo; Richt, Jürgen A; Ma, Wenjun

    2012-11-01

    Both H9N2 avian influenza and 2009 pandemic H1N1 viruses (pH1N1) are able to infect humans and swine, which has raised concerns that novel reassortant H9 viruses with pH1N1 genes might be generated in these hosts by reassortment. Although previous studies have demonstrated that reassortant H9 viruses with pH1N1 genes show increased virulence in mice and transmissibility in ferrets, the virulence and transmissibility of reassortant H9 viruses in natural hosts such as chickens and swine remain unknown. This study generated two reassortant H9 viruses (H9N2/CA09 and H9N1/CA09) in the background of the pH1N1 A/California/04/2009 (CA09) virus by replacing either both the haemagglutinin (HA) and neuraminidase (NA) genes or only the HA gene with the respective genes from the A/quail/Hong Kong/G1/1997 (H9N2) virus and evaluated their replication, pathogenicity and transmission in chickens and pigs compared with the parental viruses. Chickens that were infected with the parental H9N2 and reassortant H9 viruses seroconverted. The parental H9N2 and reassortant H9N2/CA09 viruses were transmitted to sentinel chickens, but H9N1/CA09 virus was not. The parental H9N2 replicated poorly and was not transmitted in pigs, whereas both H9N2/CA09 and H9N1/CA09 viruses replicated and were transmitted efficiently in pigs, similar to the pH1N1 virus. These results demonstrated that reassortant H9 viruses with pH1N1 genes show enhanced replication and transmissibility in pigs compared with the parental H9N2 virus, indicating that they may pose a threat for humans if such reassortants arise in swine.

  18. 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

  19. 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.

  20. Experimental infection with Brazilian Newcastle disease virus strain in pigeons and chickens

    PubMed Central

    Carrasco, Adriano de Oliveira Torres; Seki, Meire Christina; Benevenute, Jyan Lucas; Ikeda, Priscila; Pinto, Aramis Augusto

    2016-01-01

    This study was designed with the goal of adding as much information as possible about the role of pigeons (Columba livia) and chickens (Gallus gallus) in Newcastle disease virus epidemiology. These species were submitted to direct experimental infection with Newcastle disease virus to evaluate interspecies transmission and virus-host relationships. The results obtained in four experimental models were analyzed by hemagglutination inhibition and reverse transcriptase polymerase chain reaction for detection of virus shedding. These techniques revealed that both avian species, when previously immunized with a low pathogenic Newcastle disease virus strain (LaSota), developed high antibody titers that significantly reduced virus shedding after infection with a highly pathogenic Newcastle disease virus strain (São Joao do Meriti) and that, in chickens, prevent clinical signs. Infected pigeons shed the pathogenic strain, which was not detected in sentinel chickens or control birds. When the presence of Newcastle disease virus was analyzed in tissue samples by RT-PCR, in both species, the virus was most frequently found in the spleen. The vaccination regimen can prevent clinical disease in chickens and reduce viral shedding by chickens or pigeons. Biosecurity measures associated with vaccination programs are crucial to maintain a virulent Newcastle disease virus-free status in industrial poultry in Brazil. PMID:26887250

  1. Experimental infection with Brazilian Newcastle disease virus strain in pigeons and chickens.

    PubMed

    Carrasco, Adriano de Oliveira Torres; Seki, Meire Christina; Benevenute, Jyan Lucas; Ikeda, Priscila; Pinto, Aramis Augusto

    2016-01-01

    This study was designed with the goal of adding as much information as possible about the role of pigeons (Columba livia) and chickens (Gallus gallus) in Newcastle disease virus epidemiology. These species were submitted to direct experimental infection with Newcastle disease virus to evaluate interspecies transmission and virus-host relationships. The results obtained in four experimental models were analyzed by hemagglutination inhibition and reverse transcriptase polymerase chain reaction for detection of virus shedding. These techniques revealed that both avian species, when previously immunized with a low pathogenic Newcastle disease virus strain (LaSota), developed high antibody titers that significantly reduced virus shedding after infection with a highly pathogenic Newcastle disease virus strain (São Joao do Meriti) and that, in chickens, prevent clinical signs. Infected pigeons shed the pathogenic strain, which was not detected in sentinel chickens or control birds. When the presence of Newcastle disease virus was analyzed in tissue samples by RT-PCR, in both species, the virus was most frequently found in the spleen. The vaccination regimen can prevent clinical disease in chickens and reduce viral shedding by chickens or pigeons. Biosecurity measures associated with vaccination programs are crucial to maintain a virulent Newcastle disease virus-free status in industrial poultry in Brazil.

  2. 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

  3. 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 ...

  4. Pseudotyping of vesicular stomatitis virus with the envelope glycoproteins of highly pathogenic avian influenza viruses.

    PubMed

    Zimmer, Gert; Locher, Samira; Berger Rentsch, Marianne; Halbherr, Stefan J

    2014-08-01

    Pseudotype viruses are useful for studying the envelope proteins of harmful viruses. This work describes the pseudotyping of vesicular stomatitis virus (VSV) with the envelope glycoproteins of highly pathogenic avian influenza viruses. VSV lacking the homotypic glycoprotein (G) gene (VSVΔG) was used to express haemagglutinin (HA), neuraminidase (NA) or the combination of both. Propagation-competent pseudotype viruses were only obtained when HA and NA were expressed from the same vector genome. Pseudotype viruses containing HA from different H5 clades were neutralized specifically by immune sera directed against the corresponding clade. Fast and sensitive reading of test results was achieved by vector-mediated expression of GFP. Pseudotype viruses expressing a mutant VSV matrix protein showed restricted spread in IFN-competent cells. This pseudotype system will facilitate the detection of neutralizing antibodies against virulent influenza viruses, circumventing the need for high-level biosafety containment.

  5. In vivo evaluation of the pathogenicity of field isolates of infectious bronchitis virus.

    PubMed

    Avellaneda, G E; Villegas, P; Jackwood, M W; King, D J

    1994-01-01

    The pathogenicity of 13 field isolates of infectious bronchitis virus (IBV) isolated from Georgia broiler farms from 1989 to 1992 was evaluated using the IBV and Escherichia coli mixed-infection model. Based on the clinical signs, mortality, and lesions, the isolates were classified as high, intermediate, and low in pathogenicity. The in vivo classification was compared with the serotype classification results obtained by reverse transcriptase-polymerase chain reaction-restriction fragment length polymorphism analysis. The high-pathogenicity group was composed of five isolates representing three serotypes: Arkansas, Georgia variant (GAV), and Massachusetts. Isolates in the intermediate- and low-pathogenicity groups were all representatives of the Connecticut serotype, except for one isolate, which belonged to the Massachusetts serotype.

  6. 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.

  7. 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

  8. 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.

  9. Endogenous tick viruses and modulation of tick-borne pathogen growth

    PubMed Central

    Bell-Sakyi, Lesley; Attoui, Houssam

    2013-01-01

    Ticks transmit a wide range of viral, bacterial and protozoan pathogens, many of which can establish persistent infections of lifelong duration in the vector tick and in some cases are transmitted transovarially to the next generation. In addition many ixodid and argasid tick cell lines and, by inference the parent ticks from which they were derived, harbor endogenous viruses (ETV) of which almost nothing is known. In general, low level persistent infections with viral pathogens (arboviruses) are not known to have a deleterious effect on tick survival and fitness, suggesting that they can strike a balance with the tick innate immune response. This tolerance of arbovirus infection may be modulated by the permanent presence of ETV in the host cell. In mosquito cells, temporary or permanent silencing of the genes of an endogenous virus by RNA interference can result in changes in replication rate of a co-infecting arbovirus. We propose that tick cell lines offer a useful model system for in vitro investigation of the modulatory effect of ETV on superinfecting pathogen survival and replication in ticks, using the molecular manipulation techniques applied to insect cells. PMID:23875176

  10. Herpes Simplex Virus Type 1 and Other Pathogens are Key Causative Factors in Sporadic Alzheimer's Disease.

    PubMed

    Harris, Steven A; Harris, Elizabeth A

    2015-01-01

    This review focuses on research in epidemiology, neuropathology, molecular biology, and genetics regarding the hypothesis that pathogens interact with susceptibility genes and are causative in sporadic Alzheimer's disease (AD). Sporadic AD is a complex multifactorial neurodegenerative disease with evidence indicating coexisting multi-pathogen and inflammatory etiologies. There are significant associations between AD and various pathogens, including Herpes simplex virus type 1 (HSV-1), Cytomegalovirus, and other Herpesviridae, Chlamydophila pneumoniae, spirochetes, Helicobacter pylori, and various periodontal pathogens. These pathogens are able to evade destruction by the host immune system, leading to persistent infection. Bacterial and viral DNA and RNA and bacterial ligands increase the expression of pro-inflammatory molecules and activate the innate and adaptive immune systems. Evidence demonstrates that pathogens directly and indirectly induce AD pathology, including amyloid-β (Aβ) accumulation, phosphorylation of tau protein, neuronal injury, and apoptosis. Chronic brain infection with HSV-1, Chlamydophila pneumoniae, and spirochetes results in complex processes that interact to cause a vicious cycle of uncontrolled neuroinflammation and neurodegeneration. Infections such as Cytomegalovirus, Helicobacter pylori, and periodontal pathogens induce production of systemic pro-inflammatory cytokines that may cross the blood-brain barrier to promote neurodegeneration. Pathogen-induced inflammation and central nervous system accumulation of Aβ damages the blood-brain barrier, which contributes to the pathophysiology of AD. Apolipoprotein E4 (ApoE4) enhances brain infiltration by pathogens including HSV-1 and Chlamydophila pneumoniae. ApoE4 is also associated with an increased pro-inflammatory response by the immune system. Potential antimicrobial treatments for AD are discussed, including the rationale for antiviral and antibiotic clinical trials.

  11. Mammalian microRNA: an important modulator of host-pathogen interactions in human viral infections.

    PubMed

    Ojha, Chet Raj; Rodriguez, Myosotys; Dever, Seth M; Mukhopadhyay, Rita; El-Hage, Nazira

    2016-10-26

    MicroRNAs (miRNAs), which are small non-coding RNAs expressed by almost all metazoans, have key roles in the regulation of cell differentiation, organism development and gene expression. Thousands of miRNAs regulating approximately 60 % of the total human genome have been identified. They regulate genetic expression either by direct cleavage or by translational repression of the target mRNAs recognized through partial complementary base pairing. The active and functional unit of miRNA is its complex with Argonaute proteins known as the microRNA-induced silencing complex (miRISC). De-regulated miRNA expression in the human cell may contribute to a diverse group of disorders including cancer, cardiovascular dysfunctions, liver damage, immunological dysfunction, metabolic syndromes and pathogenic infections. Current day studies have revealed that miRNAs are indeed a pivotal component of host-pathogen interactions and host immune responses toward microorganisms. miRNA is emerging as a tool for genetic study, therapeutic development and diagnosis for human pathogenic infections caused by viruses, bacteria, parasites and fungi. Many pathogens can exploit the host miRNA system for their own benefit such as surviving inside the host cell, replication, pathogenesis and bypassing some host immune barriers, while some express pathogen-encoded miRNA inside the host contributing to their replication, survival and/or latency. In this review, we discuss the role and significance of miRNA in relation to some pathogenic viruses.

  12. 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...

  13. Macaque Proteome Response to Highly Pathogenic Avian Influenza and 1918 Reassortant Influenza Virus Infections▿ †

    PubMed Central

    Brown, Joseph N.; Palermo, Robert E.; Baskin, Carole R.; Gritsenko, Marina; Sabourin, Patrick J.; Long, James P.; Sabourin, Carol L.; Bielefeldt-Ohmann, Helle; García-Sastre, Adolfo; Albrecht, Randy; Tumpey, Terrence M.; Jacobs, Jon M.; Smith, Richard D.; Katze, Michael G.

    2010-01-01

    The host proteome response and molecular mechanisms that drive disease in vivo during infection by a human isolate of the highly pathogenic avian influenza virus (HPAI) and 1918 pandemic influenza virus remain poorly understood. This study presents a comprehensive characterization of the proteome response in cynomolgus macaque (Macaca fascicularis) lung tissue over 7 days of infection with HPAI (the most virulent), a reassortant virus containing 1918 hemagglutinin and neuraminidase surface proteins (intermediate virulence), or a human seasonal strain (least virulent). A high-sensitivity two-dimensional liquid chromatography-tandem mass spectroscopy strategy and functional network analysis were implemented to gain insight into response pathways activated in macaques during influenza virus infection. A macaque protein database was assembled and used in the identification of 35,239 unique peptide sequences corresponding to approximately 4,259 proteins. Quantitative analysis identified an increase in expression of 400 proteins during viral infection. The abundance levels of a subset of these 400 proteins produced strong correlations with disease progression observed in the macaques, distinguishing a “core” response to viral infection from a “high” response specific to severe disease. Proteome expression profiles revealed distinct temporal response kinetics between viral strains, with HPAI inducing the most rapid response. While proteins involved in the immune response, metabolism, and transport were increased rapidly in the lung by HPAI, the other viruses produced a delayed response, characterized by an increase in proteins involved in oxidative phosphorylation, RNA processing, and translation. Proteomic results were integrated with previous genomic and pathological analysis to characterize the dynamic nature of the influenza virus infection process. PMID:20844032

  14. Transcriptomic analysis of responses to infectious salmon anemia virus infection in macrophage-like cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The aquatic orthomyxovirus infectious salmon anemia virus (ISAV) is an important pathogen for salmonid aquaculture, however little is known about protective and pathological host responses to infection. We have investigated intracellular responses during cytopathic ISAV infection in the macrophage-l...

  15. The Drug Targets and Antiviral Molecules for Treatment of Ebola Virus Infection.

    PubMed

    Wu, Wenjiao; Liu, Shuwen

    2017-01-01

    Ebola virus (EBOV) is a highly pathogenic virus causing severe hemorrhagic fever with a high case fatality rate of 50% - 90% in humans. Without an approved vaccine or treatments, Ebola outbreak management has been limited to palliative care and barrier methods to prevent transmission. These approaches, however, have yet to end the 2014 outbreak of Ebola after its prolonged presence in West Africa. As with the increase of outbreaks, a significant effort has been made to develop promising countermeasures for the prevention and treatment of Ebola virus infection. In this review, development of therapeutics and potential inhibitors for Ebola virus infection will be discussed.

  16. 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

  17. 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

  18. Respiratory disease outbreak in a veterinary hospital associated with canine parainfluenza virus infection

    PubMed Central

    Weese, J. Scott; Stull, Jason

    2013-01-01

    A cluster of canine parainfluenza virus infections was identified in a veterinary referral hospital. While hospital-associated outbreaks of canine parainfluenza virus infection have not been previously reported, veterinary hospitals possess some of the same risk factors that may be present in traditional high-risk sites such as kennels. Hospital-associated transmission of canine respiratory pathogens, therefore, must be considered. PMID:23814307

  19. 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.

  20. Environmental Persistence Influences Infection Dynamics for a Butterfly Pathogen

    PubMed Central

    Altizer, Sonia; Williams, Mary-Kate; Hall, Richard J.

    2017-01-01

    Many pathogens, including those infecting insects, are transmitted via dormant stages shed into the environment, where they must persist until encountering a susceptible host. Understanding how abiotic conditions influence environmental persistence and how these factors influence pathogen spread are crucial for predicting patterns of infection risk. Here, we explored the consequences of environmental transmission for infection dynamics of a debilitating protozoan parasite (Ophryocystis elektroscirrha) that infects monarch butterflies (Danaus plexippus). We first conducted an experiment to observe the persistence of protozoan spores exposed to natural conditions. Experimental results showed that, contrary to our expectations, pathogen doses maintained high infectivity even after 16 days in the environment, although pathogens did yield infections with lower parasite loads after environmental exposure. Because pathogen longevity exceeded the time span of our experiment, we developed a mechanistic model to better explore environmental persistence for this host-pathogen system. Model analysis showed that, in general, longer spore persistence led to higher infection prevalence and slightly smaller monarch population sizes. The model indicated that typical parasite doses shed onto milkweed plants must remain viable for a minimum of 3 weeks for prevalence to increase during the summer-breeding season, and for 11 weeks or longer to match levels of infection commonly reported from the wild, assuming moderate values for parasite shedding rate. Our findings showed that transmission stages of this butterfly pathogen are long-lived and indicated that this is a necessary condition for the protozoan to persist in local monarch populations. This study provides a modeling framework for future work examining the dynamics of an ecologically important pathogen in an iconic insect. PMID:28099501

  1. Sparse evidence for equine or avian influenza virus infections among Mongolian adults with animal exposures.

    PubMed

    Khurelbaatar, Nyamdavaa; Krueger, Whitney S; Heil, Gary L; Darmaa, Badarchiin; Ulziimaa, Daramragchaa; Tserennorov, Damdindorj; Baterdene, Ariungerel; Anderson, Benjamin D; Gray, Gregory C

    2013-11-01

    In recent years, Mongolia has experienced recurrent epizootics of equine influenza virus (EIV) among its 2·1 million horses and multiple incursions of highly pathogenic avian influenza (HPAI) virus via migrating birds. No human EIV or HPAI infections have been reported. In 2009, 439 adults in Mongolia were enrolled in a population-based study of zoonotic influenza transmission. Enrollment sera were examined for serological evidence of infection with nine avian, three human, and one equine influenza virus strains. Seroreactivity was sparse among participants suggesting little human risk of zoonotic influenza infection.

  2. Pathogenic Differences between Nipah Virus Bangladesh and Malaysia Strains in Primates: Implications for Antibody Therapy

    PubMed Central

    Mire, Chad E.; Satterfield, Benjamin A.; Geisbert, Joan B.; Agans, Krystle N.; Borisevich, Viktoriya; Yan, Lianying; Chan, Yee-Peng; Cross, Robert W.; Fenton, Karla A.; Broder, Christopher C.; Geisbert, Thomas W.

    2016-01-01

    Nipah virus (NiV) is a paramyxovirus that causes severe disease in humans and animals. There are two distinct strains of NiV, Malaysia (NiVM) and Bangladesh (NiVB). Differences in transmission patterns and mortality rates suggest that NiVB may be more pathogenic than NiVM. To investigate pathogenic differences between strains, 4 African green monkeys (AGM) were exposed to NiVM and 4 AGMs were exposed to NiVB. While NiVB was uniformly lethal, only 50% of NiVM-infected animals succumbed to infection. Histopathology of lungs and spleens from NiVB-infected AGMs was significantly more severe than NiVM-infected animals. Importantly, a second study utilizing 11 AGMs showed that the therapeutic window for human monoclonal antibody m102.4, previously shown to rescue AGMs from NiVM infection, was much shorter in NiVB-infected AGMs. Together, these data show that NiVB is more pathogenic in AGMs under identical experimental conditions and suggests that postexposure treatments may need to be NiV strain specific for optimal efficacy. PMID:27484128

  3. [Interspecies transmission, adaptation to humans and pathogenicity of animal influenza viruses].

    PubMed

    Munier, S; Moisy, D; Marc, D; Naffakh, N

    2010-04-01

    The emergence in 2009 of a novel A(H1N1)v influenza virus of swine origin and the regular occurrence since 2003 of human cases of infection with A(H5N1) avian influenza viruses underline the zoonotic and pandemic potential of type A influenza viruses. Influenza viruses from the wild aquatic birds reservoir usually do not replicate efficiently in humans. Domestic poultry and swine can act as intermediate hosts for the acquisition of determinants that increase the potential of transmission and adaptation to humans, through the accumulation of mutations or by genetic reassortment. The rapid evolution of influenza viruses following interspecies transmission probably results from the selection of genetic variations that favor optimal interactions between viral proteins and cellular factors, leading to an increased multiplication potential and a better escape to the host antiviral response. Whereas influenza viruses usually cause asymptomatic infections in wild aquatic birds, they may be highly pathogenic in other species. Molecular determinants of host-specificity and pathogenesis have been identified in most viral genes, notably in genes that encode viral surface glycoproteins, proteins involved in the viral genome replication, and proteins that counteract the host immune response. However, our knowledge of these numerous and interdependant determinants remains incomplete, and the molecular mechanisms involved are still to be understood.

  4. 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

  5. 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.

  6. Pathogenicity, Transmission and Antigenic Variation of H5N1 Highly Pathogenic Avian Influenza Viruses.

    PubMed

    Jiao, Peirong; Song, Hui; Liu, Xiaoke; Song, Yafen; Cui, Jin; Wu, Siyu; Ye, Jiaqi; Qu, Nanan; Zhang, Tiemin; Liao, Ming

    2016-01-01

    H5N1 highly pathogenic avian influenza (HPAI) was one of the most important avian diseases in poultry production of China, especially in Guangdong province. In recent years, new H5N1 highly pathogenic avian influenza viruses (HPAIV) still emerged constantly, although all poultry in China were immunized with H5N1 vaccinations compulsorily. To better understand the pathogenicity and transmission of dominant clades of the H5N1 HPAIVs in chicken from Guangdong in 2012, we chose a clade 7.2 avian influenza virus named A/Chicken/China/G2/2012(H5N1) (G2) and a clade 2.3.2.1 avian influenza virus named A/Duck/China/G3/2012(H5N1) (G3) in our study. Our results showed that the chickens inoculated with 10(3) EID50 of G2 or G3 viruses all died, and the titers of virus replication detected in several visceral organs were high but different. In the naive contact groups, virus shedding was not detected in G2 group and all chickens survived, but virus shedding was detected in G3 group and all chickens died. These results showed that the two clades of H5N1 HPAIVs had high pathogenicity in chickens and the contact transmission of them was different in chickens. The results of cross reactive HI assay showed that antigens of G2 and G3 were very different from those of current commercial vaccines isolates (Re-4, Re-6, and D7). And to evaluate the protective efficacy of three vaccines against most isolates form Guangdong belonging to clade 2.3.2.1 in 2012, G3 was chosen to challenge the three vaccines such as Re-4, Re-6, and D7. First, chickens were immunized with 0.3 ml Re-4, Re-6, and D7 inactivated vaccines by intramuscular injection, respectively, and then challenged with 10(6) EID50 of G3 on day 28 post-vaccination. The D7 vaccine had 100% protection against G3 for chickens, the Re-6 vaccine had 88.9%, and the Re-4 vaccine only had 66.7%. Our results suggested that the D7 vaccine could prevent and control H5N1 virus outbreaks more effectively in Guangdong. From the above, it was

  7. Pathogenicity, Transmission and Antigenic Variation of H5N1 Highly Pathogenic Avian Influenza Viruses

    PubMed Central

    Jiao, Peirong; Song, Hui; Liu, Xiaoke; Song, Yafen; Cui, Jin; Wu, Siyu; Ye, Jiaqi; Qu, Nanan; Zhang, Tiemin; Liao, Ming

    2016-01-01

    H5N1 highly pathogenic avian influenza (HPAI) was one of the most important avian diseases in poultry production of China, especially in Guangdong province. In recent years, new H5N1 highly pathogenic avian influenza viruses (HPAIV) still emerged constantly, although all poultry in China were immunized with H5N1 vaccinations compulsorily. To better understand the pathogenicity and transmission of dominant clades of the H5N1 HPAIVs in chicken from Guangdong in 2012, we chose a clade 7.2 avian influenza virus named A/Chicken/China/G2/2012(H5N1) (G2) and a clade 2.3.2.1 avian influenza virus named A/Duck/China/G3/2012(H5N1) (G3) in our study. Our results showed that the chickens inoculated with 103 EID50 of G2 or G3 viruses all died, and the titers of virus replication detected in several visceral organs were high but different. In the naive contact groups, virus shedding was not detected in G2 group and all chickens survived, but virus shedding was detected in G3 group and all chickens died. These results showed that the two clades of H5N1 HPAIVs had high pathogenicity in chickens and the contact transmission of them was different in chickens. The results of cross reactive HI assay showed that antigens of G2 and G3 were very different from those of current commercial vaccines isolates (Re-4, Re-6, and D7). And to evaluate the protective efficacy of three vaccines against most isolates form Guangdong belonging to clade 2.3.2.1 in 2012, G3 was chosen to challenge the three vaccines such as Re-4, Re-6, and D7. First, chickens were immunized with 0.3 ml Re-4, Re-6, and D7 inactivated vaccines by intramuscular injection, respectively, and then challenged with 106 EID50 of G3 on day 28 post-vaccination. The D7 vaccine had 100% protection against G3 for chickens, the Re-6 vaccine had 88.9%, and the Re-4 vaccine only had 66.7%. Our results suggested that the D7 vaccine could prevent and control H5N1 virus outbreaks more effectively in Guangdong. From the above, it was

  8. Phytohormone pathways as targets of pathogens to facilitate infection.

    PubMed

    Ma, Ka-Wai; Ma, Wenbo

    2016-08-01

    Plants are constantly threatened by potential pathogens. In order to optimize the output of defense against pathogens with distinct lifestyles, plants depend on hormonal networks to fine-tune specific responses and regulate growth-defense tradeoffs. To counteract, pathogens have evolved various strategies to disturb hormonal homeostasis and facilitate infection. Many pathogens synthesize plant hormones; more importantly, toxins and effectors are produced to manipulate hormonal crosstalk. Accumulating evidence has shown that pathogens exert extensive effects on plant hormone pathways not only to defeat immunity, but also modify habitat structure, optimize nutrient acquisition, and facilitate pathogen dissemination. In this review, we summarize mechanisms by which a wide array of pathogens gain benefits from manipulating plant hormone pathways.

  9. Novel Reassortant H5N6 Influenza A Virus from the Lao People’s Democratic Republic Is Highly Pathogenic in Chickens

    PubMed Central

    Layton, Daniel S.; Phommachanh, Phouvong; Harper, Jennifer; Payne, Jean; Evans, Ryan M.; Valdeter, Stacey; Walker, Som; Harvey, Gemma; Shan, Songhua; Bruce, Matthew P.; Rootes, Christina L.; Gough, Tamara J.; Rohringer, Andreas; Peck, Grantley R.; Fardy, Sarah J.; Karpala, Adam J.; Johnson, Dayna; Wang, Jianning; Douangngeun, Bounlom; Morrissy, Christopher; Wong, Frank Y. K.; Bean, Andrew G. D.; Bingham, John; Williams, David T.

    2016-01-01

    Avian influenza viruses of H5 subtype can cause highly pathogenic disease in poultry. In March 2014, a new reassortant H5N6 subtype highly pathogenic avian influenza virus emerged in Lao People’s Democratic Republic. We have assessed the pathogenicity, pathobiology and immunological responses associated with this virus in chickens. Infection caused moderate to advanced disease in 6 of 6 chickens within 48 h of mucosal inoculation. High virus titers were observed in blood and tissues (kidney, spleen, liver, duodenum, heart, brain and lung) taken at euthanasia. Viral antigen was detected in endothelium, neurons, myocardium, lymphoid tissues and other cell types. Pro-inflammatory cytokines were elevated compared to non-infected birds. Our study confirmed that this new H5N6 reassortant is highly pathogenic, causing disease in chickens similar to that of Asian H5N1 viruses, and demonstrated the ability of such clade 2.3.4-origin H5 viruses to reassort with non-N1 subtype viruses while maintaining a fit and infectious phenotype. Recent detection of influenza H5N6 poultry infections in Lao PDR, China and Viet Nam, as well as six fatal human infections in China, demonstrate that these emergent highly pathogenic H5N6 viruses may be widely established in several countries and represent an emerging threat to poultry and human populations. PMID:27631618

  10. Isolation, Identification, and Sequencing of a Goose-Derived Newcastle Disease Virus and Determination of Its Pathogenicity.

    PubMed

    Chen, Xiao-Qing; Li, Zi-Bing; Hu, Gui-Xue; Gu, Song-Zhi; Zhang, Shuang; Ying, Ying; Gao, Feng-Shan

    2015-06-01

    In August 2010, geese in the Meihekou area of Jilin province in China were found to be infected by a pathogen that caused a disease similar to Newcastle disease. To determine the causative agent of the infections, a virus was isolated from liver tissues of infected geese, followed by a pathogenicity determination. The isolated virus was named NDV/White Goose/China/Jilin(Meihekou)/MHK-1/2010. Specific primers were designed to amplify the whole genome of the MHK-1 virus, followed by sequencing and splicing of the entire genome. Sequencing and phylogenetic analysis of MHK-1 showed that the isolate was a virulent strain of Newcastle disease virus. The MHK-1 genome is 15,192 nucleotides long, and it belongs to the class II branch of Newcastle disease viruses, as evidenced by the amino acid sequence (112R-R-Q-K-R-F117) of the F protein. The hemagglutinin titer was 1:128 to 1:512. The chicken embryo mean death time, the intracerebral pathogenicity index, and the median lethal dose of chicken embryos of MHK-1 were 43 hr, 1.63, and 10(9)/ml, respectively, which revealed that the newly isolated MHK-1 strain is strongly pathogenic to geese.

  11. RNA Editing of the GP Gene of Ebola Virus is an Important Pathogenicity Factor.

    PubMed

    Volchkova, Valentina A; Dolnik, Olga; Martinez, Mikel J; Reynard, Olivier; Volchkov, Viktor E

    2015-10-01

    Synthesis of the surface glycoprotein GP of Ebola virus (EBOV) is dependent on transcriptional RNA editing, whereas direct expression of the GP gene results in synthesis of nonstructural secreted glycoprotein sGP. In this study, we investigate the role of RNA editing in the pathogenicity of EBOV using a guinea pig model and recombinant guinea pig-adapted EBOV containing mutations at the editing site, allowing expression of surface GP without the need for RNA editing, and also preventing synthesis of sGP. We demonstrate that the elimination of the editing site leads to EBOV attenuation in vivo, explained by lower virus spread caused by the higher virus cytotoxicity and, most likely, by an increased ability of the host defense systems to recognize and eliminate virus-infected cells. We also demonstrate that expression of sGP does not affect pathogenicity of EBOV in guinea pigs. In conclusion, data obtained indicate that downregulation of the level of surface GP expression through a mechanism of GP gene RNA editing plays an important role in the high pathogenicity of EBOV.

  12. Detection of viral respiratory pathogens in mild and severe acute respiratory infections in Singapore

    PubMed Central

    Jiang, Lili; Lee, Vernon Jian Ming; Cui, Lin; Lin, Raymond; Tan, Chyi Lin; Tan, Linda Wei Lin; Lim, Wei-yen; Leo, Yee-Sin; Low, Louie; Hibberd, Martin; Chen, Mark I-Cheng

    2017-01-01

    To investigate the performance of laboratory methods and clinical case definitions in detecting the viral pathogens for acute respiratory infections (ARIs) from a prospective community cohort and hospital inpatients, nasopharyngeal swabs from cohort members reporting ARIs (community-ARI) and inpatients admitted with ARIs (inpatient-ARI) were tested by Singleplex Real Time-Polymerase Chain Reaction (SRT-PCR), multiplex RT-PCR (MRT-PCR) and pathogen-chip system (PathChip) between April 2012 and December 2013. Community-ARI and inpatient-ARI was also combined with mild and severe cases of influenza from a historical prospective study as mild-ARI and severe-ARI respectively to evaluate the performance of clinical case definitions. We analysed 130 community-ARI and 140 inpatient-ARI episodes (5 inpatient-ARI excluded because multiple pathogens were detected), involving 138 and 207 samples respectively. Detection by PCR declined with days post-onset for influenza virus; decrease was faster for community-ARI than for inpatient-ARI. No such patterns were observed for non-influenza respiratory virus infections. PathChip added substantially to viruses detected for community-ARI only. Clinical case definitions discriminated influenza from other mild-ARI but performed poorly for severe-ARI and for older participants. Rational strategies for diagnosis and surveillance of influenza and other respiratory virus must acknowledge the differences between ARIs presenting in community and hospital settings. PMID:28218288

  13. Sustained live poultry market surveillance contributes to early warnings for human infection with avian influenza viruses

    PubMed Central

    Fang, Shisong; Bai, Tian; Yang, Lei; Wang, Xin; Peng, Bo; Liu, Hui; Geng, Yijie; Zhang, Renli; Ma, Hanwu; Zhu, Wenfei; Wang, Dayan; Cheng, Jinquan; Shu, Yuelong

    2016-01-01

    Sporadic human infections with the highly pathogenic avian influenza (HPAI) A (H5N6) virus have been reported in different provinces in China since April 2014. From June 2015 to January 2016, routine live poultry market (LPM) surveillance was conducted in Shenzhen, Guangdong Province. H5N6 viruses were not detected until November 2015. The H5N6 virus-positive rate increased markedly beginning in December 2015, and viruses were detected in LPMs in all districts of the city. Coincidently, two human cases with histories of poultry exposure developed symptoms and were diagnosed as H5N6-positive in Shenzhen during late December 2015 and early January 2016. Similar viruses were identified in environmental samples collected in the LPMs and the patients. In contrast to previously reported H5N6 viruses, viruses with six internal genes derived from the H9N2 or H7N9 viruses were detected in the present study. The increased H5N6 virus-positive rate in the LPMs and the subsequent human infections demonstrated that sustained LPM surveillance for avian influenza viruses provides an early warning for human infections. Interventions, such as LPM closures, should be immediately implemented to reduce the risk of human infection with the H5N6 virus when the virus is widely detected during LPM surveillance. PMID:27485495

  14. Sustained live poultry market surveillance contributes to early warnings for human infection with avian influenza viruses.

    PubMed

    Fang, Shisong; Bai, Tian; Yang, Lei; Wang, Xin; Peng, Bo; Liu, Hui; Geng, Yijie; Zhang, Renli; Ma, Hanwu; Zhu, Wenfei; Wang, Dayan; Cheng, Jinquan; Shu, Yuelong

    2016-08-03

    Sporadic human infections with the highly pathogenic avian influenza (HPAI) A (H5N6) virus have been reported in different provinces in China since April 2014. From June 2015 to January 2016, routine live poultry market (LPM) surveillance was conducted in Shenzhen, Guangdong Province. H5N6 viruses were not detected until November 2015. The H5N6 virus-positive rate increased markedly beginning in December 2015, and viruses were detected in LPMs in all districts of the city. Coincidently, two human cases with histories of poultry exposure developed symptoms and were diagnosed as H5N6-positive in Shenzhen during late December 2015 and early January 2016. Similar viruses were identified in environmental samples collected in the LPMs and the patients. In contrast to previously reported H5N6 viruses, viruses with six internal genes derived from the H9N2 or H7N9 viruses were detected in the present study. The increased H5N6 virus-positive rate in the LPMs and the subsequent human infections demonstrated that sustained LPM surveillance for avian influenza viruses provides an early warning for human infections. Interventions, such as LPM closures, should be immediately implemented to reduce the risk of human infection with the H5N6 virus when the virus is widely detected during LPM surveillance.

  15. Differential Host Response, Rather Than Early Viral Replication Efficiency, Correlates with Pathogenicity Caused by Influenza Viruses

    PubMed Central

    Askovich, Peter S.; Sanders, Catherine J.; Rosenberger, Carrie M.; Diercks, Alan H.; Dash, Pradyot; Navarro, Garnet; Vogel, Peter; Doherty, Peter C.; Thomas, Paul G.; Aderem, Alan

    2013-01-01

    Influenza viruses exhibit large, strain-dependent differences in pathogenicity in mammalian hosts. Although the characteristics of severe disease, including uncontrolled viral replication, infection of the lower airway, and highly inflammatory cytokine responses have been extensively documented, the specific virulence mechanisms that distinguish highly pathogenic strains remain elusive. In this study, we focused on the early events in influenza infection, measuring the growth rate of three strains of varying pathogenicity in the mouse airway epithelium and simultaneously examining the global host transcriptional response over the first 24 hours. Although all strains replicated equally rapidly over the first viral life-cycle, their growth rates in both lung and tracheal tissue strongly diverged at later times, resulting in nearly 10-fold differences in viral load by 24 hours following infection. We identified separate networks of genes in both the lung and tracheal tissues whose rapid up-regulation at early time points by specific strains correlated with a reduced viral replication rate of those strains. The set of early-induced genes in the lung that led to viral growth restriction is enriched for both NF-κB binding site motifs and members of the TREM1 and IL-17 signaling pathways, suggesting that rapid, NF-κB –mediated activation of these pathways may contribute to control of viral replication. Because influenza infection extending into the lung generally results in severe disease, early activation of these pathways may be one factor distinguishing high- and low-pathogenicity strains. PMID:24073225

  16. Phylogenetic analysis and pathogenicity of H3 subtype avian influenza viruses isolated from live poultry markets in China

    PubMed Central

    Cui, Hongrui; Shi, Ying; Ruan, Tao; Li, Xuesong; Teng, Qiaoyang; Chen, Hongjun; Yang, Jianmei; Liu, Qinfang; Li, Zejun

    2016-01-01

    H3 subtype influenza A virus is one of the main subtypes that threats both public and animal health. However, the evolution and pathogenicity of H3 avian influenza virus (AIV) circulating in domestic birds in China remain largely unclear. In this study, seven H3 AIVs (four H3N2 and three H3N8) were isolated from poultry in live poultry market (LPM) in China. Phylogenetic analyses of full genomes showed that all viruses were clustered into Eurasian lineage, except N8 genes of two H3N8 isolates fell into North American lineage. Intriguingly, the N8 gene of one H3N8 and PB2, PB1, NP and NS of two H3N2 isolates have close relationship with those of the highly pathogenic H5N8 viruses circulating in Korea and United States, suggesting that the H3-like AIV may contribute internal genes to the highly pathogenic H5N8 viruses. Phylogenetic tree of HA gene and antigenic cross-reactivity results indicated that two antigenically different H3 viruses are circulating in LPM in China. Most of the H3 viruses replicated in mice lung and nasal turbinate without prior adaptation, and the representative H3 viruses infected chickens without causing clinical signs. The reassortment of H3 subtype influenza viruses warrants continuous surveillance in LPM in China. PMID:27270298

  17. Surveillance for highly pathogenic avian influenza virus in wild birds during outbreaks in domestic poultry, Minnesota, 2015

    USGS Publications Warehouse

    Jennelle, Christopher S.; Carstensen, Michelle; Hildebrand, Erik C.; Cornicelli, Louis; Wolf, Paul C.; Grear, Daniel A.; Ip, Hon S.; VanDalen, Kaci K.; Minicucci, Larissa A.

    2016-01-01

    In 2015, a major outbreak of highly pathogenic avian influenza virus (HPAIV) infection devastated poultry facilities in Minnesota, USA. To clarify the role of wild birds, we tested 3,139 waterfowl fecal samples and 104 sick and dead birds during March 9–June 4, 2015. HPAIV was isolated from a Cooper’s hawk but not from waterfowl.

  18. Pathogenicity of three type 2 Porcine Reproductive and Respiratory Syndrome virus strains in experimentally inoculated pregnant gilts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mechanisms of reproductive failure resulting from infection with porcine reproductive and respiratory syndrome virus (PRRSv) are still poorly understood. The present study, a side-by-side evaluation of the pathogenicity of three type 2 PRRSv strains in a reproductive model, was used as a pilot study...

  19. 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.

  20. Reduction in airborne virus using modifications of simulated home slaughter of asymptomatic H5N1 HPAI virus infected chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: The majority of human infections with H5N1 high pathogenicity avian influenza (HPAI) virus have occurred in the village setting of developing countries with the primary exposure risk being direct contact with live or dead poultry in the household or neighborhood. In Egypt, the majority o...

  1. Impacts of allergic airway inflammation on lung pathology in a mouse model of influenza A virus infection

    PubMed Central

    Kawaguchi, Akira; Ohara, Yuki; Takahashi, Kenta; Sato, Yuko; Ainai, Akira; Nagata, Noriyo; Tashiro, Masato; Hasegawa, Hideki

    2017-01-01

    Influenza A virus is the respiratory pathogen responsible for influenza. Infection by the 2009 pandemic influenza A (H1N1) virus caused severe lower airway inflammation and pneumonia. Asthma is a chronic inflammatory disorder of the airways that affects the entire brachial tree, and was one of the commonest underlying medical conditions among patients hospitalized with the 2009 pandemic influenza virus infection. Although respiratory virus infections are the major causes of asthma exacerbation, the mechanism by which influenza exacerbates asthma is poorly understood. Animal models of disease comorbidity are crucial to understanding host-pathogen interactions and elucidating complex pathologies. Existing murine models of influenza virus infection in asthmatics show that asthmatic mice are highly resistant to influenza virus infection, which contradicts clinical observations in humans. Here, we developed a murine model of influenza virus/asthma comorbidity using NC/Nga mice, which are highly sensitive to allergic reactions such as atopic dermatitis and allergic airway inflammation. This model was then used to examine the impact of allergic airway inflammation on lung pathology in the 2009 pandemic influenza virus infected mice. The results showed that induction of acute allergic airway inflammation in pre-existing influenza virus infection had additive effects on exacerbation of lung pathology, which mirrors findings in human epidemiological studies. In contrast, pre-existing allergic airway inflammation protected from subsequent influenza virus infection, which was compatible with those of previous murine models of influenza virus infection in asthmatic mice. These variable outcomes of this murine model indicate that the temporal relation between allergic airway inflammation and influenza virus infection might play a critical role in asthma and influenza comorbidity. Thus, this murine model will further our understanding of how influenza virus infection affects an

  2. 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

  3. Pathobiological Characterization of a Novel Reassortant Highly Pathogenic H5N1 Virus Isolated in British Columbia, Canada, 2015

    PubMed Central

    Berhane, Yohannes; Kobasa, Darwyn; Embury-Hyatt, Carissa; Pickering, Brad; Babiuk, Shawn; Joseph, Tomy; Bowes, Victoria; Suderman, Mathew; Leung, Anders; Cottam-Birt, Colleen; Hisanaga, Tamiko; Pasick, John

    2016-01-01

    In the current study, we describe the pathobiologic characteristics of a novel reassortant virus - A/chicken/BC/FAV-002/2015 (H5N1) belonging to clade 2.3.4.4 that was isolated from backyard chickens in British Columbia, Canada. Sequence analyses demonstrate PB1, PA, NA and NS gene segments were of North American lineage while PB2, HA, NP and M were derived from a Eurasian lineage H5N8 virus. This novel virus had a 19 amino acid deletion in the neuraminidase stalk. We evaluated the pathogenic potential of this isolate in various animal models. The virus was highly pathogenic to mice with a LD50 of 10 plaque forming units (PFU), but had limited tissue tropism. It caused only subclinical infection in pigs which did result in seroconversion. This virus was highly pathogenic to chickens, turkeys, juvenile Muscovy ducks (Cairnia moschata foma domestica) and adult Chinese geese (Anser cynoides domesticus) causing a systemic infection in all species. The virus was also efficiently transmitted and resulted in mortality in naïve contact ducks, geese and chickens. Our findings indicate that this novel H5N1 virus has a wide host range and enhanced surveillance of migratory waterfowl may be necessary in order to determine its potential to establish itself in the wild bird reservoir. PMID:26988892

  4. 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.

  5. 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.

  6. The host immune response in respiratory virus infection: balancing virus clearance and immunopathology.

    PubMed

    Newton, Amy H; Cardani, Amber; Braciale, Thomas J

    2016-07-01

    The respiratory tract is constantly exposed to the external environment, and therefore, must be equipped to respond to and eliminate pathogens. Viral clearance and resolution of infection requires a complex, multi-faceted response initiated by resident respiratory tract cells and innate immune cells and ultimately resolved by adaptive immune cells. Although an effective immune response to eliminate viral pathogens is essential, a prolonged or exaggerated response can damage the respiratory tract. Immune-mediated pulmonary damage is manifested clinically in a variety of ways depending on location and extent of injury. Thus, the antiviral immune response represents a balancing act between the elimination of virus and immune-mediated pulmonary injury. In this review, we highlight major components of the host response to acute viral infection and their role in contributing to mitigating respiratory damage. We also briefly describe common clinical manifestations of respiratory viral infection and morphological correlates. The continuing threat posed by pandemic influenza as well as the emergence of novel respiratory viruses also capable of producing severe acute lung injury such as SARS-CoV, MERS-CoV, and enterovirus D68, highlights the need for an understanding of the immune mechanisms that contribute to virus elimination and immune-mediated injury.

  7. 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

  8. Widespread detection of highly pathogenic H5 influenza viruses in wild birds from the Pacific Flyway of the United States

    PubMed Central

    Bevins, S. N.; Dusek, R. J.; White, C. L.; Gidlewski, T.; Bodenstein, B.; Mansfield, K. G.; DeBruyn, P.; Kraege, D.; Rowan, E.; Gillin, C.; Thomas, B.; Chandler, S.; Baroch, J.; Schmit, B.; Grady, M. J.; Miller, R. S.; Drew, M. L.; Stopak, S.; Zscheile, B.; Bennett, J.; Sengl, J.; Brady, Caroline; Ip, H. S.; Spackman, E.; Killian, M. L.; Torchetti, M. K.; Sleeman, J. M.; Deliberto, T. J.

    2016-01-01

    A novel highly pathogenic avian influenza virus belonging to the H5 clade 2.3.4.4 variant viruses was detected in North America in late 2014. Motivated by the identification of these viruses in domestic poultry in Canada, an intensive study was initiated to conduct highly pathogenic avian influenza surveillance in wild birds in the Pacific Flyway of the United States. A total of 4,729 hunter-harvested wild birds were sampled and highly pathogenic avian influenza virus was detected in 1.3% (n = 63). Three H5 clade 2.3.4.4 subtypes were isolated from wild birds, H5N2, H5N8, and H5N1, representing the wholly Eurasian lineage H5N8 and two novel reassortant viruses. Testing of 150 additional wild birds during avian morbidity and mortality investigations in Washington yielded 10 (6.7%) additional highly pathogenic avian influenza isolates (H5N8 = 3 and H5N2 = 7). The geographically widespread detection of these viruses in apparently healthy wild waterfowl suggest that the H5 clade 2.3.4.4 variant viruses may behave similarly in this taxonomic group whereby many waterfowl species are susceptible to infection but do not demonstrate obvious clinical disease. Despite these findings in wild waterfowl, mortality has been documented for some wild bird species and losses in US domestic poultry during the first half of 2015 were unprecedented. PMID:27381241

  9. Widespread detection of highly pathogenic H5 influenza viruses in wild birds from the Pacific Flyway of the United States

    USGS Publications Warehouse

    Bevins, S.N.; Dusek, Robert J.; White, C. LeAnn; Gidlewski, Thomas; Bodenstein, B.; Mansfield, Kristin G.; DeBruyn, Paul; Kraege, Donald K.; Rowan, E.L.; Gillin, Colin; Thomas, B.; Chandler, S.; Baroch, J.; Schmit, B.; Grady, M. J.; Miller, R. S.; Drew, M.L.; Stopak, S.; Zscheile, B.; Bennett, J.; Sengl, J.; Brady, Caroline; Ip, Hon S.; Spackman, Erica; Killian, M. L.; Kim Torchetti, Mia; Sleeman, Jonathan M.; DeLiberto, T.J.

    2016-01-01

    A novel highly pathogenic avian influenza virus belonging to the H5 clade 2.3.4.4 variant viruses was detected in North America in late 2014. Motivated by the identification of these viruses in domestic poultry in Canada, an intensive study was initiated to conduct highly pathogenic avian influenza surveillance in wild birds in the Pacific Flyway of the United States. A total of 4,729 hunter-harvested wild birds were sampled and highly pathogenic avian influenza virus was detected in 1.3% (n = 63). Three H5 clade 2.3.4.4 subtypes were isolated from wild birds, H5N2, H5N8, and H5N1, representing the wholly Eurasian lineage H5N8 and two novel reassortant viruses. Testing of 150 additional wild birds during avian morbidity and mortality investigations in Washington yielded 10 (6.7%) additional highly pathogenic avian influenza isolates (H5N8 = 3 and H5N2 = 7). The geographically widespread detection of these viruses in apparently healthy wild waterfowl suggest that the H5 clade 2.3.4.4 variant viruses may behave similarly in this taxonomic group whereby many waterfowl species are susceptible to infection but do not demonstrate obvious clinical disease. Despite these findings in wild waterfowl, mortality has been documented for some wild bird species and losses in US domestic poultry during the first half of 2015 were unprecedented.

  10. 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

  11. 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.

  12. 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.

  13. Tissue tropism of highly pathogenic avian influenza virus subtype H5N1 in naturally infected mute swans (Cygnus Olor ), domestic geese (Aser Anser var. domestica), pekin ducks (Anas platyrhynchos) and mulard ducks ( Cairina moschata x anas platyrhynchos).

    PubMed

    Szeredi, Levente; Dán, Adám; Pálmai, Nimród; Ursu, Krisztina; Bálint, Adám; Szeleczky, Zsófia; Ivanics, Eva; Erdélyi, Károly; Rigó, Dóra; Tekes, Lajos; Glávits, Róbert

    2010-03-01

    The 2006 epidemic due to highly pathogenic avian influenza virus (HPAIV) subtype H5N1 in Hungary caused the most severe losses in waterfowl which were, according to the literature at the time, supposed to be the most resistant to this pathogen. The presence of pathological lesions and the amount of viral antigen were quantified by gross pathology, histopathology and immunohistochemistry (IHC) in the organs of four waterfowl species [mute swans (n = 10), domestic geese (n = 6), mulard ducks (n = 6) and Pekin ducks (n = 5)] collected during the epidemic. H5N1 subtype HPAIV was isolated from all birds examined. Quantitative real-time reverse transcriptase-polymerase chain reaction (qRRT-PCR) was also applied on a subset of samples [domestic geese (n = 3), mulard (n = 4) and Pekin duck (n = 4)] in order to compare its sensitivity with IHC. Viral antigen was detected by IHC in all cases. However, the overall presence of viral antigen in tissue samples was quite variable: virus antigen was present in 56/81 (69%) swan, 22/38 (58%) goose, 28/46 (61%) mulard duck and 5/43 (12%) Pekin duck tissue samples. HPAIV subtype H5N1 was detected by qRRT-PCR in all birds examined, in 19/19 (100%) goose, 7/28 (25%) mulard duck and 12/28 (43%) Pekin duck tissue samples. As compared to qRRTPCR, the IHC was less sensitive in geese and Pekin ducks but more sensitive in mulard ducks. The IHC was consistently positive above 4.31 log10 copies/reaction but it gave very variable results below that level. Neurotropism of the isolated virus strains was demonstrated by finding the largest amount of viral antigen and the highest average RNA load in the brain in all four waterfowl species examined.

  14. 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.

  15. An H5N1 highly pathogenic avian influenza virus that invaded Japan through waterfowl migration.

    PubMed

    Kajihara, Masahiro; Matsuno, Keita; Simulundu, Edgar; Muramatsu, Mieko; Noyori, Osamu; Manzoor, Rashid; Nakayama, Eri; Igarashi, Manabu; Tomabechi, Daisuke; Yoshida, Reiko; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Ito, Kimihito; Kida, Hiroshi; Takada, Ayato

    2011-08-01

    In 2010, an H5N1 highly pathogenic avian influenza virus (HPAIV) was isolated from feces of apparently healthy ducks migrating southward in Hokkaido, the northernmost prefecture of Japan. The H5N1 HPAIVs were subsequently detected in domestic and wild birds at multiple sites corresponding to the flyway of the waterfowl having stopovers in the Japanese archipelago. The Hokkaido isolate was genetically nearly identical to H5N1 HPAIVs isolated from swans in the spring of 2009 and 2010 in Mongolia, but less pathogenic in experimentally infected ducks than the 2009 Mongolian isolate. These findings suggest that H5N1 HPAIVs with relatively mild pathogenicity might be selected and harbored in the waterfowl population during the 2009-2010 migration seasons. Our data provide "early warning" signals for preparedness against the unprecedented situation in which the waterfowl reservoirs serve as perpetual sources and disseminators of HPAIVs.

  16. 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.

  17. Genome Wide Host Gene Expression Analysis in Chicken Lungs Infected with Avian Influenza Viruses

    PubMed Central

    Gandhale, Pradeep N.; Kumar, Himanshu; Kulkarni, Diwakar D.

    2016-01-01

    The molecular pathogenesis of avian influenza infection varies greatly with individual bird species and virus strain. The molecular pathogenesis of the highly pathogenic avian influenza virus (HPAIV) or the low pathogenic avian influenza virus (LPAIV) infection in avian species remains poorly understood. Thus, global immune response of chickens infected with HPAI H5N1 (A/duck/India/02CA10/2011) and LPAI H9N2 (A/duck/India/249800/2010) viruses was studied using microarray to identify crucial host genetic components responsive to these infection. HPAI H5N1 virus induced excessive expression of type I IFNs (IFNA and IFNG), cytokines (IL1B, IL18, IL22, IL13, and IL12B), chemokines (CCL4, CCL19, CCL10, and CX3CL1) and IFN stimulated genes (OASL, MX1, RSAD2, IFITM5, IFIT5, GBP 1, and EIF2AK) in lung tissues. This dysregulation of host innate immune genes may be the critical determinant of the severity and the outcome of the influenza infection in chickens. In contrast, the expression levels of most of these genes was not induced in the lungs of LPAI H9N2 virus infected chickens. This study indicated the relationship between host immune genes and their roles in pathogenesis of HPAIV infection in chickens. PMID:27071061

  18. Genome Wide Host Gene Expression Analysis in Chicken Lungs Infected with Avian Influenza Viruses.

    PubMed

    Ranaware, Pradip B; Mishra, Anamika; Vijayakumar, Periyasamy; Gandhale, Pradeep N; Kumar, Himanshu; Kulkarni, Diwakar D; Raut, Ashwin Ashok

    2016-01-01

    The molecular pathogenesis of avian influenza infection varies greatly with individual bird species and virus strain. The molecular pathogenesis of the highly pathogenic avian influenza virus (HPAIV) or the low pathogenic avian influenza virus (LPAIV) infection in avian species remains poorly understood. Thus, global immune response of chickens infected with HPAI H5N1 (A/duck/India/02CA10/2011) and LPAI H9N2 (A/duck/India/249800/2010) viruses was studied using microarray to identify crucial host genetic components responsive to these infection. HPAI H5N1 virus induced excessive expression of type I IFNs (IFNA and IFNG), cytokines (IL1B, IL18, IL22, IL13, and IL12B), chemokines (CCL4, CCL19, CCL10, and CX3CL1) and IFN stimulated genes (OASL, MX1, RSAD2, IFITM5, IFIT5, GBP 1, and EIF2AK) in lung tissues. This dysregulation of host innate immune genes may be the critical determinant of the severity and the outcome of the influenza infection in chickens. In contrast, the expression levels of most of these genes was not induced in the lungs of LPAI H9N2 virus infected chickens. This study indicated the relationship between host immune genes and their roles in pathogenesis of HPAIV infection in chickens.

  19. 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.

  20. 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

  1. Hyaluronan synthesis in virus PBCV-1-infected chlorella-like green algae.

    PubMed

    Graves, M V; Burbank, D E; Roth, R; Heuser, J; DeAngelis, P L; Van Etten, J L

    1999-04-25

    We previously reported that the chlorella virus PBCV-1 genome encodes an authentic, membrane-associated glycosyltransferase, hyaluronan synthase (HAS). Hyaluronan, a linear polysaccharide chain composed of alternating beta1,4-glucuronic acid and beta1, 3-N-acetylglucosamine groups, is present in vertebrates as well as a few pathogenic bacteria. Studies of infected cells show that the transcription of the PBCV-1 has gene begins within 10 min of virus infection and ends at 60-90 min postinfection. The hyaluronan polysaccharide begins to accumulate as hyaluronan-lyase sensitive, hair-like fibers on the outside of the chlorella cell wall by 15-30 min postinfection; by 240 min postinfection, the infected cells are coated with a dense fibrous network. This hyaluronan slightly reduces attachment of a second chlorella virus to the infected algae. An analysis of 41 additional chlorella viruses indicates that many, but not all, produce hyaluronan during infection.

  2. A Network Integration Approach to Predict Conserved Regulators Related to Pathogenicity of Influenza and SARS-CoV Respiratory Viruses

    SciTech Connect

    Mitchell, Hugh D.; Eisfeld, Amie J.; Sims, Amy; McDermott, Jason E.; Matzke, Melissa M.; Webb-Robertson, Bobbie-Jo M.; Tilton, Susan C.; Tchitchek, Nicholas; Josset, Laurence; Li, Chengjun; Ellis, Amy L.; Chang, Jean H.; Heegel, Robert A.; Luna, Maria L.; Schepmoes, Athena A.; Shukla, Anil K.; Metz, Thomas O.; Neumann, Gabriele; Benecke, Arndt; Smith, Richard D.; Baric, Ralph; Kawaoka, Yoshihiro; Katze, Michael G.; Waters, Katrina M.

    2013-07-25

    Respiratory infections stemming from influenza viruses and the Severe Acute Respiratory Syndrome corona virus (SARS-CoV) represent a serious public health threat as emerging pandemics. Despite efforts to identify the critical interactions of these viruses with host machinery, the key regulatory events that lead to disease pathology remain poorly targeted with therapeutics. Here we implement an integrated network interrogation approach, in which proteome and transcriptome datasets from infection of both viruses in human lung epithelial cells are utilized to predict regulatory genes involved in the host response. We take advantage of a novel “crowd-based” approach to identify and combine ranking metrics that isolate genes/proteins likely related to the pathogenicity of SARS-CoV and influenza virus. Subsequently, a multivariate regression model is used to compare predicted lung epithelial regulatory influences with data derived from other respiratory virus infection models. We predicted a small set of regulatory factors with conserved behavior for consideration as important components of viral pathogenesis that might also serve as therapeutic targets for intervention. Our results demonstrate the utility of integrating diverse ‘omic datasets to predict and prioritize regulatory features conserved across multiple pathogen infection models.

  3. A Network Integration Approach to Predict Conserved Regulators Related to Pathogenicity of Influenza and SARS-CoV Respiratory Viruses

    PubMed Central

    Mitchell, Hugh D.; Eisfeld, Amie J.; Sims, Amy C.; McDermott, Jason E.; Matzke, Melissa M.; Webb-Robertson, Bobbi-Jo M.; Tilton, Susan C.; Tchitchek, Nicolas; Josset, Laurence; Li, Chengjun; Ellis, Amy L.; Chang, Jean H.; Heegel, Robert A.; Luna, Maria L.; Schepmoes, Athena A.; Shukla, Anil K.; Metz, Thomas O.; Neumann, Gabriele; Benecke, Arndt G.; Smith, Richard D.; Baric, Ralph S.; Kawaoka, Yoshihiro; Katze, Michael G.; Waters, Katrina M.

    2013-01-01

    Respiratory infections stemming from influenza viruses and the Severe Acute Respiratory Syndrome corona virus (SARS-CoV) represent a serious public health threat as emerging pandemics. Despite efforts to identify the critical interactions of these viruses with host machinery, the key regulatory events that lead to disease pathology remain poorly targeted with therapeutics. Here we implement an integrated network interrogation approach, in which proteome and transcriptome datasets from infection of both viruses in human lung epithelial cells are utilized to predict regulatory genes involved in the host response. We take advantage of a novel “crowd-based” approach to identify and combine ranking metrics that isolate genes/proteins likely related to the pathogenicity of SARS-CoV and influenza virus. Subsequently, a multivariate regression model is used to compare predicted lung epithelial regulatory influences with data derived from other respiratory virus infection models. We predicted a small set of regulatory factors with conserved behavior for consideration as important components of viral pathogenesis that might also serve as therapeutic targets for intervention. Our results demonstrate the utility of integrating diverse ‘omic datasets to predict and prioritize regulatory features conserved across multiple pathogen infection models. PMID:23935999

  4. Biologic characterization of chicken-derived H6N2 low pathogenic avian influenza viruses in chickens and ducks.

    PubMed

    Jackwood, Mark W; Suarez, David L; Hilt, Deborah; Pantin-Jackwood, Mary J; Spackman, Erica; Woolcock, Peter; Cardona, Carol

    2010-03-01

    Low pathogenic avian influenza H6N2 viruses were biologically characterized by infecting chickens and ducks in order to compare adaptation of these viruses in these species. We examined the clinical signs, virus shedding, and immune response to infection in 4-wk-old white leghorn chickens and in 2-wk-old Pekin ducks. Five H6N2 viruses isolated between 2000 and 2004 from chickens in California, and one H6N2 virus isolated from chickens in New York in 1998, were given intrachoanally at a dose of 1 x 10(6) 50% embryo infectious dose per bird. Oral-pharyngeal and cloacal swabs were taken at 2, 4, and 7 days postinoculation (PI) and tested by real-time reverse-transcriptase polymerase chain reaction for presence of virus. Serum was collected at 7, 14, and 21 days PI and examined for avian influenza virus antibodies by commercial enzyme-linked immunosorbent assay (ELISA) and hemagglutination inhibition (HI) testing. Virus shedding for all of the viruses was detected in the oral-pharyngeal swabs from chickens at 2 and 4 days PI, but only three of the five viruses were detected at 7 days PI. Only two viruses were detected in the cloacal swabs from the chickens. Virus shedding for four of the five viruses was detected in the oral-pharyngeal cavity of the ducks, and fecal shedding was detected for three of the viruses (including the virus not shed by the oral-pharyngeal route) in ducks at 4 and 7 days PI. All other fecal swabs from the ducks were negative. Fewer ducks shed virus compared to chickens. Both the chickens and the ducks developed antibodies, as evidenced by HI and ELISA titers. The data indicate that the H6N2 viruses can infect both chickens and ducks, but based on the number of birds shedding virus and on histopathology, the viruses appear to be more adapted to chickens. Virus shedding, which could go unnoticed in the absence of clinical signs in commercial chickens, can lead to transmission of the virus among poultry. However, the viruses isolated in 2004 did

  5. 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

  6. Propagation of field highly pathogenic porcine reproductive and respiratory syndrome virus in MARC-145 cells is promoted by cell apoptosis.

    PubMed

    Ge, Mengyun; Zhang, Yi; Liu, Ying; Liu, Tao; Zeng, Fanya

    2016-02-02

    Infection of porcine reproductive and respiratory syndrome virus (PRRSV) induces cell apoptosis both in vivo and in vitro. However, the correlation between host cell apoptosis and PRRSV replication is unclear. Here, the promotion of PRRSV propagation by cell apoptosis in MARC-145 cells was reported. The observation on propagation of field highly pathogenic PRRSV (HP-PRRSV) in MARC-145 cells showed that infection of overgrown MARC-145 cells obviously elevated virus production and cell apoptosis was triggered in these cells before virus inoculation. The investigation on propagation of field HP-PRRSV in apoptosis induced MARC-145 cells displayed that induction of apoptosis further increased the virus production and a vigorous viral RNA replication accompanied by fast virus release in these cells was detected in the initial 24h post infection. In addition, when field HP-PRRSV was serially passed in drug-treated MARC-145 cells, the progeny viruses kept a stable viral titer and infectivity to its native target cells in the tested generations. In summary, these findings demonstrated that apoptotic MARC-145 cells were more susceptible to field HP-PRRSV and propagation of the virus was promoted by effective replication and cell-to-cell transmission of the virus in these cells.

  7. 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.

  8. Heterogeneous and Dynamic Prevalence of Asymptomatic Influenza Virus Infections

    PubMed Central

    Furuya-Kanamori, Luis; Cox, Mitchell; Milinovich, Gabriel J.; Magalhaes, Ricardo J. Soares; Mackay, Ian M.

    2016-01-01

    Influenza infection manifests in a wide spectrum of severity, including symptomless pathogen carriers. We conducted a systematic review and meta-analysis of 55 studies to elucidate the proportional representation of these asymptomatic infected persons. We observed extensive heterogeneity among these studies. The prevalence of asymptomatic carriage (total absence of symptoms) ranged from 5.2% to 35.5% and subclinical cases (illness that did not meet the criteria for acute respiratory or influenza-like illness) from 25.4% to 61.8%. Statistical analysis showed that the heterogeneity could not be explained by the type of influenza, the laboratory tests used to detect the virus, the year of the study, or the location of the study. Projections of infection spread and strategies for disease control require that we identify the proportional representation of these insidious spreaders early on in the emergence of new influenza subtypes or strains and track how this rate evolves over time and space. PMID:27191967

  9. [Pulmonary complications in children with human immunodeficiency virus infection].

    PubMed

    Brockmann V, Pablo; Viviani S, Támara; Peña D, Anamaría

    2007-08-01

    Pulmonary complications in children infected by human immunodeficiency virus (HIV) are common and may be the first manifestation of acquired immunodeficiency syndrome (AIDS). The aim of our study was to review pulmonary diseases and complications in pediatric patients with HIV infection in a large tertiary hospital in Santiago, Chile. We performed a retrospective, descriptive analysis of 17 patients with HIV infection controlled at the Hospital Dr. Sótero del Rio. Respiratory complications/diseases were: overall pneumonia (n: 14), recurrent pneumonia (n: 10), citomegalovirus associated pneumonia (n: 4), Pneumocystis jiroveci associated pneumonia (n: 1) pulmonary tuberculosis (n: 1), lymphoid interstitial pneumonia (n: 3) and chronic pulmonary disease (n: 7). Microorganisms isolated were mostly atypical and frequently associated with severe and chronic pulmonary damage. A high degree of suspicion is required to detect atypical microorganisms promptly, in order to rapidly implement pathogen targeted therapy that could potentially decrease the possibility of sequelae.

  10. 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.

  11. Antiretroviral Therapy in Simian Immunodeficiency Virus-Infected Sooty Mangabeys: Implications for AIDS Pathogenesis

    PubMed Central

    Calascibetta, Francesca; Micci, Luca; Carnathan, Diane; Lawson, Benton; Vanderford, Thomas H.; Bosinger, Steven E.; Easley, Kirk; Chahroudi, Ann; Mackel, Joseph; Keele, Brandon F.; Long, Samuel; Lifson, Jeffrey; Paiardini, Mirko

    2016-01-01

    ABSTRACT Simian immunodeficiency virus (SIV)-infected sooty mangabeys (SMs) do not develop AIDS despite high levels of viremia. Key factors involved in the benign course of SIV infection in SMs are the absence of chronic immune activation and low levels of infection of CD4+ central memory (TCM) and stem cell memory (TSCM) T cells. To better understand the role of virus replication in determining the main features of SIV infection in SMs, we treated 12 SMs with a potent antiretroviral therapy (ART) regimen for 2 to 12 months. We observed that ART suppressed viremia to <60 copies/ml of plasma in 10 of 12 animals and induced a variable decrease in the level of cell-associated SIV DNA in peripheral blood (average changes of 0.9-, 1.1-, 1.5-, and 3.7-fold for CD4+ transitional memory [TTM], TCM, effector memory [TEM], and TSCM cells, respectively). ART-treated SIV-infected SMs showed (i) increased percentages of circulating CD4+ TCM cells, (ii) increased levels of CD4+ T cells in the rectal mucosa, and (iii) significant declines in the frequencies of HLA-DR+ CD8+ T cells in the blood and rectal mucosa. In addition, we observed that ART interruption resulted in rapid viral rebound in all SIV-infected SMs, indicating that the virus reservoir persists for at least a year under ART despite lower infection levels of CD4+ TCM and TSCM cells than those seen in pathogenic SIV infections of macaques. Overall, these data indicate that ART induces specific immunological changes in SIV-infected SMs, thus suggesting that virus replication affects immune function even in the context of this clinically benign infection. IMPORTANCE Studies of natural, nonpathogenic simian immunodeficiency virus (SIV) infection of African monkeys have provided important insights into the mechanisms responsible for the progression to AIDS during pathogenic human immunodeficiency virus (HIV) infection of humans and SIV infection of Asian macaques. In this study, for the first time, we treated SIV-infected

  12. Tembusu virus infection in Cherry Valley ducks: the effect of age at infection.

    PubMed

    Sun, X Y; Diao, Y X; Wang, J; Liu, X; Lu, A L; Zhang, L; Ge, P P; Hao, D M

    2014-01-10

    Three groups of Cherry Valley ducks at 5 day, 2 week and 5 week of age were intranasally infected with the WFCL strain of Tembusu virus (TMUV) to investigate the effect of host age on the outcome of TMUV infection. For each age group, clinical signs, gross and microscopic lesions, viral copy numbers in tissues and serum neutralizing antibody titers were recorded. Age-related differences in the resistance to TMUV infection were observed with younger ducks being more susceptible. Some ducks infected at 5 day and 2 week of age developed severe clinical signs, including severe neurological dysfunction and death. However, subclinical signs and no mortality were observed in ducks infected at 5 week of age. A decline in the severity of gross and microscopic lesions was observed as ducks mature. Systemic infections were established in the three age groups post challenge. Higher viral copy numbers in the tissues, especially in vital organs such as the brain and the heart, were developed in the ducks infected at 5 day of age than older ducks, correlating with the severity of clinical signs and lesions in the tissues. Furthermore, ducks infected at 5 week of age developed significantly higher serum neutralizing antibody titers than ducks infected at 5 day of age as determined by serum neutralization test. Therefore, age-related differences in the resistance to TMUV infection should be considered when studying the pathogenicity, pathogenesis, formulation of the vaccination and therapy strategies of TMUV infection in ducks.

  13. Changes in adaptation of H5N2 highly pathogenic avian influenza H5 clade 2.3.4.4 viruses in chickens and mallards

    Technology Transfer Automated Retrieval System (TEKTRAN)

    H5N2 highly pathogenic avian influenza (HPAI) viruses caused a severe poultry outbreak in the United States (U.S.) during 2015. In order to examine changes in adaptation of this viral lineage, the infectivity, transmission and pathogenesis of poultry H5N2 viruses was investigated in chickens and mal...

  14. Susceptibility of five migratory aquatic birds to H5N1 highly pathogenic avian influenza virus (A/Chicken/Korea/IS/06)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It is not known which migratory aquatic species are important in spreading H5N1 highly pathogenic avian influenza (HPAI) viruses, and the pathobiology of infections by such viruses. The objective of this investigation was to assess the susceptibility of Mute swans (Cygnus olor), Greylag geese (Anse...

  15. Reduction of high pathogenicity avian influenza virus in eggs from chickens once or twice vaccinated with an oil-emulsified inactivated H5 avian influenza vaccine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The negative impact of high pathogenicity avian influenza virus (HPAIV) infection on egg production and deposition of virus in eggs, as well as any protective effect of vaccination, is unknown. Individually housed non-vaccinated, sham-vaccinated and inactivated H5N9 vaccinated once or twice adult Wh...

  16. Ferrets develop fatal influenza after inhaling small particle aerosols of highly pathogenic avian influenza virus A/Vietnam/1203/2004 (H5N1)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There is limited knowledge about the potential routes for H5N1 influenza virus transmission to and between humans, and it is not clear whether humans can be infected through inhalation of aerosolized H5N1 virus particles. Ferrets are often used as a surrogate for humans in influenza pathogenicity a...

  17. 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 activation of the AKT/mTOR pathways in PRV infected cells. These findings suggest that autophagy likely contributes to clearance of PRV, and that the virus has evolved strategies to antagonize this pathway. PMID:28059118

  18. Borrelia Diversity and Co-infection with Other Tick Borne Pathogens in Ticks

    PubMed Central

    Raileanu, Cristian; Moutailler, Sara; Pavel, Ionuţ; Porea, Daniela; Mihalca, Andrei D.; Savuta, Gheorghe; Vayssier-Taussat, Muriel

    2017-01-01

    Identifying Borrelia burgdorferi as the causative agent of Lyme disease in 1981 was a watershed moment in understanding the major impact that tick-borne zoonoses can have on public health worldwide, particularly in Europe and the USA. The medical importance of tick-borne diseases has long since been acknowledged, yet little is known regarding the occurrence of emerging tick-borne pathogens such as Borrelia spp., Anaplasma phagocytophilum, Rickettsia spp., Bartonella spp., “Candidatus Neoehrlichia mikurensis”, and tick-borne encephalitis virus in questing ticks in Romania, a gateway into Europe. The objective of our study was to identify the infection and co-infection rates of different Borrelia genospecies along with other tick-borne pathogens in questing ticks collected from three geographically distinct areas in eastern Romania. We collected 557 questing adult and nymph ticks of three different species (534 Ixodes ricinus, 19 Haemaphysalis punctata, and 4 Dermacentor reticulatus) from three areas in Romania. We analyzed ticks individually for the presence of eight different Borrelia genospecies with high-throughput real-time PCR. Ticks with Borrelia were then tested for possible co-infections with A. phagocytophilum, Rickettsia spp., Bartonella spp., “Candidatus Neoehrlichia mikurensis”, and tick-borne encephalitis virus. Borrelia spp. was detected in I. ricinus ticks from all sampling areas, with global prevalence rates of 25.8%. All eight Borrelia genospecies were detected in I. ricinus ticks: Borrelia garinii (14.8%), B. afzelii (8.8%), B. valaisiana (5.1%), B. lusitaniae (4.9%), B. miyamotoi (0.9%), B. burgdorferi s.s (0.4%), and B. bissettii (0.2%). Regarding pathogen co-infection 64.5% of infected I. ricinus were positive for more than one pathogen. Associations between different Borrelia genospecies were detected in 9.7% of ticks, and 6.9% of I. ricinus ticks tested positive for co-infection of Borrelia spp. with other tick-borne pathogens. The

  19. Antibody Responses to Zika Virus Infections in Environments of Flavivirus Endemicity.

    PubMed

    Keasey, Sarah L; Pugh, Christine L; Jensen, Stig M R; Smith, Jessica L; Hontz, Robert D; Durbin, Anna P; Dudley, Dawn M; O'Connor, David H; Ulrich, Robert G

    2017-04-01

    Zika virus (ZIKV) infections occur in areas where dengue virus (DENV), West Nile virus (WNV), yellow fever virus (YFV), and other viruses of the genus Flavivirus cocirculate. The envelope (E) proteins of these closely related flaviviruses induce specific long-term immunity, yet subsequent infections are associated with cross-reactive antibody responses that may enhance disease susceptibility and severity. To gain a better understanding of ZIKV infections against a background of similar viral diseases, we examined serological immune responses to ZIKV, WNV, DENV, and YFV infections of humans and nonhuman primates (NHPs). Using printed microarrays, we detected very specific antibody responses to primary infections with probes of recombinant E proteins from 15 species and lineages of flaviviruses pathogenic to humans, while high cross-reactivity between ZIKV and DENV was observed with 11 printed native viruses. Notably, antibodies from human primary ZIKV or secondary DENV infections that occurred in areas where flavivirus is endemic broadly recognized E proteins from many flaviviruses, especially DENV, indicating a strong influence of infection history on immune responses. A predictive algorithm was used to tentatively identify previous encounters with specific flaviviruses based on serum antibody interactions with the multispecies panel of E proteins. These results illustrate the potential impact of exposure to related viruses on the outcome of ZIKV infection and offer considerations for development of vaccines and diagnostics.

  20. 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

  1. 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.

  2. Host behaviour and physiology underpin individual variation in avian influenza virus infection in migratory Bewick's swans

    PubMed Central

    Hoye, Bethany J.; Fouchier, Ron A. M.; Klaassen, Marcel

    2012-01-01

    Individual variation in infection modulates both the dynamics of pathogens and their impact on host populations. It is therefore crucial to identify differential patterns of infection and understand the mechanisms responsible. Yet our understanding of infection heterogeneity in wildlife is limited, even for important zoonotic host–pathogen systems, owing to the intractability of host status prior to infection. Using novel applications of stable isotope ecology and eco-immunology, we distinguish antecedent behavioural and physiological traits associated with avian influenza virus (AIV) infection in free-living Bewick's swans (Cygnus columbianus bewickii). Swans infected with AIV exhibited higher serum δ13C (−25.3 ± 0.4) than their non-infected counterparts (−26.3 ± 0.2). Thus, individuals preferentially foraging in aquatic rather than terrestrial habitats experienced a higher risk of infection, suggesting that the abiotic requirements of AIV give rise to heterogeneity in pathogen exposure. Juveniles were more likely to be infected (30.8% compared with 11.3% for adults), shed approximately 15-fold higher quantity of virus and exhibited a lower specific immune response than adults. Together, these results demonstrate the potential for heterogeneity in infection to have a profound influence on the dynamics of pathogens, with concomitant impacts on host habitat selection and fitness. PMID:21733894

  3. 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.

  4. 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.

  5. 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.

  6. Characterization of low pathogenicity H5N1 avian influenza viruses from North America

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Wild bird surveillance in North America for avian influenza (AI) viruses with a goal of early identification of the Asian H5N1 highly pathogenic AI virus has identified at least six low pathogenic H5N1 AI viruses between 2004 and 2006. The hemagglutinin (HA) and neuraminidase (NA) genes from all 6 ...

  7. 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

  8. 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.

  9. Extended transmission of two H5/H7 low pathogenic avian influenza viruses in chickens.

    PubMed

    Claes, G; Lambrecht, B; Dewulf, J; van den Berg, T; Marché, S

    2015-03-01

    Transmission experiments are useful for investigating the mechanisms of low pathogenic notifiable avian influenza virus (LPNAI) transmission. In this study, the hypothesis that inoculation-infected chickens are more infectious than contact-infected chickens was tested. To this end, extended transmission experiments with one H5N2 and one H7N1 LPAIV which had previously been characterized in a series of standard transmission experiments were conducted in specific pathogen-free (SPF) chickens. For the H5N2 LPAIV, the infectivity of contact-infected chickens was similar to the infectivity of inoculated chickens. Despite results from a previous study suggesting the H7N1 LPAIV strain to be similarly infectious to SPF chickens as the H5N2 LPAIV strain, the acquisition of contact-infected chickens proved more difficult for H7N1 LPAIV. It was assumed that this might have been a consequence of the length and timing of the exposure period. In conclusion, for LPNAIVs that first seemed equally infectious, short-term transmissibility may vary considerably.

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

    PubMed

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

    2016-06-16

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

  11. Immunohistochemistry for the diagnosis of hepatitis E virus infection.

    PubMed

    Gupta, P; Jagya, N; Pabhu, S B; Durgapal, H; Acharya, S K; Panda, S K

    2012-02-01

    Hepatitis E virus (HEV) is an emerging pathogen and the most common cause of acute viral hepatitis all over the world. We describe here an immunohistochemical method for the detection of HEV antigens (pORF2 and pORF3) in formalin-fixed, paraffin-embedded liver tissues using monoclonal antibodies raised against two of the virus proteins (pORF2 and pORF3). We analysed their specificity and sensitivity in comparison with serology and nucleic acid detection in cases of acute liver failure (ALF). We used this test on 30 liver biopsies collected post-mortem from the patients of ALF caused by HEV infection. These cases were selected on the basis of positive results for enzyme immunoassay (IgM anti-HEV). Of the 30 cases taken from the archives of the Department of Pathology, the antibodies successfully stained all. However, only 25 serum samples (83.3%) of these were positive for HEV RNA. Fifteen controls used (Five noninfected liver tissues, five HBV- and five hepatitis C virus-infected liver tissues) were all negative. The immunohistochemical assay described here may prove a valuable tool for the detection of HEV infection in biopsy, autopsy and explant liver tissues and can serve as a link along with other available tests to delineate the extent of HEV-associated problem worldwide.

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

    PubMed Central

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

    2016-01-01

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

  13. 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

  14. 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.

  15. 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)

  16. 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

  17. 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

  18. 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.

  19. Differential induction of CCL5 by pathogenic and non-pathogenic strains of West Nile virus in brain endothelial cells and astrocytes

    PubMed Central

    Hussmann, Katherine L.

    2014-01-01

    The neuroinflammatory response to West Nile virus (WNV) infection can be either protective or pathological depending on the context. Although several studies have examined chemokine profiles within brains of WNV-infected mice, little is known about how various cell types within the central nervous system (CNS) contribute to chemokine expression. Here, we assessed chemokine expression in brain microvascular endothelial cells and astrocytes, which comprise the major components of the blood–brain barrier (BBB), in response to a non-pathogenic