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Sample records for pathogens cytomegalovirus influenza

  1. Schizophrenia Susceptibility Genes Directly Implicated in the Life Cycles of Pathogens: Cytomegalovirus, Influenza, Herpes simplex, Rubella, and Toxoplasma gondii

    PubMed Central

    Carter, C.J.

    2009-01-01

    Many genes implicated in schizophrenia can be related to glutamatergic transmission and neuroplasticity, oligodendrocyte function, and other families clearly related to neurobiology and schizophrenia phenotypes. Others appear rather to be involved in the life cycles of the pathogens implicated in the disease. For example, aspartylglucosaminidase (AGA), PLA2, SIAT8B, GALNT7, or B3GAT1 metabolize chemical ligands to which the influenza virus, herpes simplex, cytomegalovirus (CMV), rubella, or Toxoplasma gondii bind. The epidermal growth factor receptor (EGR/EGFR) is used by the CMV to gain entry to cells, and a CMV gene codes for an interleukin (IL-10) mimic that binds the host cognate receptor, IL10R. The fibroblast growth factor receptor (FGFR1) is used by herpes simplex. KPNA3 and RANBP5 control the nuclear import of the influenza virus. Disrupted in schizophrenia 1 (DISC1) controls the microtubule network that is used by viruses as a route to the nucleus, while DTNBP1, MUTED, and BLOC1S3 regulate endosomal to lysosomal routing that is also important in viral traffic. Neuregulin 1 activates ERBB receptors releasing a factor, EBP1, known to inhibit the influenza virus transcriptase. Other viral or bacterial components bind to genes or proteins encoded by CALR, FEZ1, FYN, HSPA1B, IL2, HTR2A, KPNA3, MED12, MED15, MICB, NQO2, PAX6, PIK3C3, RANBP5, or TP53, while the cerebral infectivity of the herpes simplex virus is modified by Apolipoprotein E (APOE). Genes encoding for proteins related to the innate immune response, including cytokine related (CCR5, CSF2RA, CSF2RB, IL1B, IL1RN, IL2, IL3, IL3RA, IL4, IL10, IL10RA, IL18RAP, lymphotoxin-alpha, tumor necrosis factor alpha [TNF]), human leukocyte antigen (HLA) antigens (HLA-A10, HLA-B, HLA-DRB1), and genes involved in antigen processing (angiotensin-converting enzyme and tripeptidyl peptidase 2) are all concerned with defense against invading pathogens. Human microRNAs (Hsa-mir-198 and Hsa-mir-206) are predicted to bind

  2. 76 FR 24793 - Highly Pathogenic Avian Influenza

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-03

    ... Inspection Service 9 CFR Parts 93, 94, and 95 RIN 0579-AC36 Highly Pathogenic Avian Influenza AGENCY: Animal... products from regions where any subtype of highly pathogenic avian influenza is considered to exist. The... vaccinated for certain types of avian influenza, or that have moved through regions where any subtype...

  3. Cytomegalovirus as an Insidious Pathogen Causing Duodenitis.

    PubMed

    Hagiya, Hideharu; Iwamuro, Masaya; Tanaka, Takehiro; Hanayama, Yoshihisa; Otsuka, Fumio

    2015-01-01

    A 60-year-old woman with rheumatoid arthritis treated with methotrexate for a decade complained of slight epigastric discomfort. A positive cytomegalovirus (CMV) antigenemia test indicated the probability of CMV-related gastrointestinal infection, for which esophagogastroduodenoscopy was performed. Endoscopic findings showed a non-specific duodenal mucosal lesion;however, pathological investigation revealed evidence of CMV duodenitis. There is scarce information on the clinical and pathological features of CMV-related duodenitis, likely due to its low prevalence. CMV infection in the upper gastrointestinal tract should be considered as a differential diagnosis in high-risk individuals, particularly those with symptoms relating to the digestive system. Biopsy examinations are preferable for the definitive diagnosis of CMV gastrointestinal infection, even without specific endoscopic features. PMID:26490030

  4. 76 FR 4046 - Highly Pathogenic Avian Influenza

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-24

    ...We are amending the regulations concerning the importation of animals and animal products to prohibit or restrict the importation of bird and poultry products from regions where any subtype of highly pathogenic avian influenza is considered to exist. We are also adding restrictions concerning importation of live poultry and birds that have been vaccinated for certain types of avian influenza,......

  5. 77 FR 34783 - Highly Pathogenic Avian Influenza

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-12

    ... avian influenza (HPAI). On January 24, 2011, we published in the Federal Register (76 FR 4046-4056... Avian Influenza AGENCY: Animal and Plant Health Inspection Service, USDA. ACTION: Interim rule... importation of bird and poultry products from regions where any subtype of highly pathogenic avian...

  6. Human cytomegalovirus (CMV) in Africa: a neglected but important pathogen.

    PubMed

    Bates, Matthew; Brantsaeter, Arne Broch

    2016-01-01

    In Africa, human cytomegalovirus (CMV) is an important pathogen in a diverse range of patient groups. Congenital CMV infection is common, and most children undergo primary infection during the first year of life. Preliminary studies suggest that these early primary CMV infections could have population-wide effects on growth and development. In most studies of adults, CMV seroprevalence is close to 100%, but some studies have found that significant minorities of adults are seronegative. CMV is a common cause of pneumonia and meningitis in hospitalised immunosuppressed patient groups, and CMV DNAemia may be an important marker of rapid progression and poor outcomes of HIV infection, despite roll-out of antiretroviral therapy (ART). Diagnosis and treatment of CMV-related disease is broadly neglected in Africa, and no randomised clinical trials of anti-CMV drugs have been conducted to date. Autopsy is rarely performed in Africa, but identifies CMV as a frequent pathogen when it is carried out. Here we review the available literature on CMV in Africa, primarily in adult patients, and discuss this in the context of contemporary understanding of CMV as a human pathogen. PMID:27482452

  7. Inactivation of Influenza A virus, Adenovirus, and Cytomegalovirus with PAXgene tissue fixative and formalin.

    PubMed

    Kap, Marcel; Arron, Georgina I; Loibner, M; Hausleitner, Anja; Siaulyte, Gintare; Zatloukal, Kurt; Murk, Jean-Luc; Riegman, Peter

    2013-08-01

    Formalin fixation is known to inactivate most viruses in a vaccine production context, but nothing is published about virus activity in tissues treated with alternative, non-crosslinking fixatives. We used a model assay based on cell culture to test formalin and PAXgene Tissue fixative for their virus-inactivating abilities. MDCK, A549, and MRC-5 cells were infected with Influenza A virus, Adenovirus, and Cytomegalovirus, respectively. When 75% of the cells showed a cytopathic effect (CPE), the cells were harvested and incubated for 15 min, or 1, 3, 6, or 24 hours, with PBS (positive control), 4% formalin, or PAXgene Tissue Fix. The cells were disrupted and the released virus was used to infect fresh MDCK, A549, and MRC-5 cells cultured on cover slips in 24-well plates. The viral cultures were monitored for CPE and by immunocytochemistry (ICC) to record viral replication and infectivity. Inactivation of Adenovirus by formalin occurred after 3 h, while Influenza A virus as well as Cytomegalovirus were inactivated by formalin after 15 min. All three virus strains were inactivated by PAXgene Tissue fixative after 15 min. We conclude that PAXgene Tissue fixative is at least as effective as formalin in inactivating infectivity of Influenza A virus, Adenovirus, and Cytomegalovirus. PMID:24845590

  8. Host genetic determinants of influenza pathogenicity

    PubMed Central

    Lin, Tsai-Yu; Brass, Abraham L.

    2014-01-01

    Despite effective vaccines, influenza remains a major global health threat due to the morbidity and mortality caused by seasonal epidemics, as well as the 2009 pandemic. Also of profound concern are the rare but potentially catastrophic transmissions of avian influenza to humans, highlighted by a recent H7N9 influenza outbreak. Murine and human studies reveal that the clinical course of influenza is the result of a combination of both host and viral genetic determinants. While viral pathogenicity has long been the subject of intensive efforts, research to elucidate host genetic determinants, particularly human, is now in the ascendant, and the goal of this review is to highlight these recent insights. PMID:23933004

  9. Cytomegalovirus (CMV) seropositivity decreases B cell responses to the influenza vaccine

    PubMed Central

    Frasca, Daniela; Diaz, Alain; Romero, Maria; Landin, Ana Marie; Blomberg, Bonnie B.

    2015-01-01

    Cytomegalovirus (CMV)-seropositivity has been shown to have a negative effect on influenza vaccine-specific antibody responses. In this paper we confirm and extend these results showing for the first time a negative association between CMV-seropositivity and B cell predictive biomarkers of optimal vaccine responses. These biomarkers are switched memory B cells and AID in CpG-stimulated B cell cultures measured before vaccination which positively correlate with the serum response to the influenza vaccine. We also found that CMV-seropositivity is associated with increased levels of B cell-intrinsic inflammation and these both correlate with lower B cell function. Finally, CMV-seropositivity is associated with decreased percentages of individuals responding to the vaccine in both young and elderly individuals. PMID:25659271

  10. USGS highly pathogenic avian influenza research strategy

    USGS Publications Warehouse

    Harris, M. Camille; Miles, A. Keith; Pearce, John M.; Prosser, Diann J.; Sleeman, Jonathan M.; Whalen, Mary E.

    2015-01-01

    Avian influenza viruses are naturally occurring in wild birds such as ducks, geese, swans, and gulls. These viruses generally do not cause illness in wild birds, however, when spread to poultry they can be highly pathogenic and cause illness and death in backyard and commercial farms. Outbreaks may cause devastating agricultural economic losses and some viral strains have the potential to infect people directly. Furthermore, the combination of avian influenza viruses with mammalian viruses can result in strains with the ability to transmit from person to person, possibly leading to viruses with pandemic potential. All known pandemic influenza viruses have had some genetic material of avian origin. Since 1996, a strain of highly pathogenic avian influenza (HPAI) virus, H5N1, has caused infection in wild birds, losses to poultry farms in Eurasia and North Africa, and led to the deaths of several hundred people. Spread of the H5N1 virus and other influenza strains from China was likely facilitated by migratory birds. In December 2014, HPAI was detected in poultry in Canada and migratory birds in the United States. Since then, HPAI viruses have spread to large parts of the United States and will likely continue to spread through migratory bird flyways and other mechanisms throughout North America. In the United States, HPAI viruses have severely affected the poultry industry with millions of domestic birds dead or culled. These strains of HPAI are not known to cause disease in humans; however, the Centers for Disease Control and Prevention (CDC) advise caution when in close contact with infected birds. Experts agree that HPAI strains currently circulating in wild birds of North America will likely persist for the next few years. This unprecedented situation presents risks to the poultry industry, natural resource management, and potentially human health. Scientific knowledge and decision support tools are urgently needed to understand factors affecting the persistence

  11. Expanding role of cytomegalovirus as a human pathogen.

    PubMed

    Navarro, David

    2016-07-01

    Cytomegalovirus (CMV) continues to be a leading cause of morbidity and mortality in transplant recipients, despite major advancements in preventative strategies. Antiviral prophylaxis and pre-emptive antiviral therapeutic regimens are associated with a high incidence of late-onset end-organ disease and cause drug-related toxicity when overused. Therefore, the identification of risk factors for CMV replication is required. Genetic and immunological factors that predispose individuals to CMV-related clinical complications have been identified and may be instrumental for optimizing CMV treatment in the future. Evidence suggests a causal pathogenetic link between CMV-related complications and inflammatory diseases in non-canonically immunosuppressed individuals such as patients with lung injury and critically ill and cancer patients. However, a randomized clinical trial is required to determine if a causal relationship exists. J. Med. Virol. 88:1103-1112, 2016. © 2015 Wiley Periodicals, Inc. PMID:26681168

  12. Rapidly Expanding Range of Highly Pathogenic Avian Influenza Viruses

    PubMed Central

    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. PMID:26079209

  13. 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.

  14. 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...

  15. Persistence of Highly Pathogenic Avian Influenza Viruses in Natural Ecosystems

    PubMed Central

    Feare, Chris J.; Renaud, François; Thomas, Frédéric; Gauthier-Clerc, Michel

    2010-01-01

    Understanding of ecologic factors favoring emergence and maintenance of highly pathogenic avian influenza (HPAI) viruses is limited. Although low pathogenic avian influenza viruses persist and evolve in wild populations, HPAI viruses evolve in domestic birds and cause economically serious epizootics that only occasionally infect wild populations. We propose that evolutionary ecology considerations can explain this apparent paradox. Host structure and transmission possibilities differ considerably between wild and domestic birds and are likely to be major determinants of virulence. Because viral fitness is highly dependent on host survival and dispersal in nature, virulent forms are unlikely to persist in wild populations if they kill hosts quickly or affect predation risk or migratory performance. Interhost transmission in water has evolved in low pathogenic influenza viruses in wild waterfowl populations. However, oropharyngeal shedding and transmission by aerosols appear more efficient for HPAI viruses among domestic birds. PMID:20587174

  16. 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...

  17. Highly Pathogenic Avian Influenza: Intersecting Humans, Animals, and the Environment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Eurasian-African H5N1 highly pathogenic avian influenza (HPAI) virus has caused an unprecedented epizootic affecting mainly poultry, but has crossed multiple species barriers to infect captive and wild birds, carnivorous mammals and humans. There is still great concern over the continued infecti...

  18. 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...

  19. Pathogenicity of two Egyptian H5N1 highly pathogenic avian influenza viruses in domestic ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Domestic ducks have been implicated in the dissemination and evolution of H5N1 highly pathogenic avian influenza (HPAI) viruses. Interestingly, the pathogenicity of H5N1 HPAI viruses in domestic ducks has increased over time with some viruses producing 100% mortality in ducks. These changes in vir...

  20. Pathogenicity of reassortant H5N1 highly pathogenic avian influenza viruses in domestic ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The pathogenicity of H5N1 highly pathogenic avian influenza (HPAI) viruses in domestic ducks has increased over time. These changes in virulence have been reported with viruses from countries with high population of domestic ducks, including Egypt. In order to understand which viral genes are contri...

  1. Outbreak of H7N8 Low Pathogenic Avian Influenza in Commercial Turkeys with Spontaneous Mutation to Highly Pathogenic Avian Influenza.

    PubMed

    Killian, Mary Lea; Kim-Torchetti, Mia; Hines, Nichole; Yingst, Sam; DeLiberto, Thomas; Lee, Dong-Hun

    2016-01-01

    Highly pathogenic avian influenza (HPAI) subtype H7N8 was detected in commercial turkeys in January 2016. Control zone surveillance discovered a progenitor low pathogenic avian influenza (LPAI) virus in surrounding turkey flocks. Data analysis supports a single LPAI virus introduction followed by spontaneous mutation to HPAI on a single premises. PMID:27313288

  2. Outbreak of H7N8 Low Pathogenic Avian Influenza in Commercial Turkeys with Spontaneous Mutation to Highly Pathogenic Avian Influenza

    PubMed Central

    Killian, Mary Lea; Hines, Nichole; Yingst, Sam; DeLiberto, Thomas; Lee, Dong-Hun

    2016-01-01

    Highly pathogenic avian influenza (HPAI) subtype H7N8 was detected in commercial turkeys in January 2016. Control zone surveillance discovered a progenitor low pathogenic avian influenza (LPAI) virus in surrounding turkey flocks. Data analysis supports a single LPAI virus introduction followed by spontaneous mutation to HPAI on a single premises. PMID:27313288

  3. Humoral response to influenza vaccination in relation to pre-vaccination antibody titres, vaccination history, cytomegalovirus serostatus and CD4/CD8 ratio.

    PubMed

    Strindhall, Jan; Ernerudh, Jan; Mörner, Andreas; Waalen, Kristian; Löfgren, Sture; Matussek, Andreas; Bengner, Malin

    2016-06-01

    Background Annual vaccination against influenza virus is generally recommended to elderly and chronically ill, but the relative importance of factors influencing the outcome is not fully understood. Methods In this study of 88 individuals all aged 69 years, the increase in haemagglutinin-inhibiting (HI) antibodies to trivalent inactivated influenza vaccine was correlated with HI titres before vaccination, prior vaccinations against influenza, cytomegalovirus serostatus and, as an estimate of immune risk profile, the ratio between CD4 + and CD8 + T cells. Results Vaccine responses were impaired by high pre-existing HI antibody titres. For influenza B repeated vaccinations and an inverse CD4/CD8 ratio had a negative impact on the vaccine response. Cytomegalovirus seropositivity had no apparent effect on HI titres before or after vaccination. Conclusions It is concluded that both pre-existing HI antibodies and previous vaccinations to influenza may influence the humoral response to influenza vaccination and that a CD4/CD8 ratio < 1 may indicate an impaired ability to respond to repeated antigenic stimulation. PMID:27030916

  4. Helping poultry and people through research on high pathogenicity avian influenza

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza (AI) viruses are a diverse group divided into 144 different subtypes based on different combinations of the 16 hemagglutinin and 9 neuraminidase subtypes, and two different pathotypes (low [LP] and high pathogenicity [HP]). Low pathogenicity avian influenza (LPAI) viruses are maintai...

  5. USGS role and response to highly pathogenic avian influenza

    USGS Publications Warehouse

    Harris, M. Camille; Miles, A. Keith; Pearce, John M.; Prosser, Diann J.; Sleeman, Jonathan M.; Whalen, Mary E.

    2015-01-01

    Avian influenza viruses are naturally occurring in wild birds such as ducks, geese, swans, and gulls. These viruses generally do not cause illness in wild birds, however, when spread to poultry they can be highly pathogenic and cause illness and death in backyard and commercial farms. Outbreaks may cause devastating agricultural economic losses and some viral strains have the potential to infect people directly. Furthermore, the combination of avian influenza viruses with mammalian viruses can result in strains with the ability to transmit from person to person, possibly leading to viruses with pandemic potential. All known pandemic influenza viruses have had some genetic material of avian origin. Since 1996, a strain of highly pathogenic avian influenza (HPAI) virus, H5N1, has caused infection in wild birds, losses to poultry farms in Eurasia and North Africa, and led to the deaths of several hundred people. Spread of the H5N1 virus and other influenza strains from China was likely facilitated by migratory birds. In December 2014, HPAI was detected in poultry in Canada and migratory birds in the United States. Since then, HPAI viruses have spread to large parts of the United States and will likely continue to spread through migratory bird flyways and other mechanisms throughout North America. In the United States, HPAI viruses have severely affected the poultry industry with millions of domestic birds dead or culled. These strains of HPAI are not known to cause disease in humans; however, the Centers for Disease Control and Prevention (CDC) advise caution when in close contact with infected birds. Experts agree that HPAI strains currently circulating in wild birds of North America will likely persist for the next few years. This unprecedented situation presents risks to the poultry industry, natural resource management, and potentially human health. Scientific knowledge and decision support tools are urgently needed to understand factors affecting the persistence

  6. 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

  7. Comparison of pathogenicities of H7 avian influenza viruses via intranasal and conjunctival inoculation in cynomolgus macaques.

    PubMed

    Shichinohe, Shintaro; Itoh, Yasushi; Nakayama, Misako; Ozaki, Hiroichi; Soda, Kosuke; Ishigaki, Hirohito; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Kida, Hiroshi; Ogasawara, Kazumasa

    2016-06-01

    The outbreak of H7N9 low pathogenic avian influenza viruses in China has attracted attention to H7 influenza virus infection in humans. Since we have shown that the pathogenicity of H1N1 and H5N1 influenza viruses in macaques was almost the same as that in humans, we compared the pathogenicities of H7 avian influenza viruses in cynomolgus macaques via intranasal and conjunctival inoculation, which mimics natural infection in humans. H7N9 virus, as well as H7N7 highly pathogenic avian influenza virus, showed more efficient replication and higher pathogenicity in macaques than did H7N1 and H7N3 highly pathogenic avian influenza viruses. These results are different from pathogenicity in chickens as reported previously. Therefore, our results obtained in macaques help to estimate the pathogenicity of H7 avian influenza viruses in humans. PMID:26994587

  8. Highly Pathogenic Avian Influenza Virus Infection of Mallards with Homo- and Heterosubtypic Immunity Induced by Low Pathogenic Avian Influenza Viruses

    PubMed Central

    Fereidouni, Sasan R.; Starick, Elke; Beer, Martin; Wilking, Hendrik; Kalthoff, Donata; Grund, Christian; Häuslaigner, Rafaela; Breithaupt, Angele; Lange, Elke; Harder, Timm C.

    2009-01-01

    The potential role of wild birds as carriers of highly pathogenic avian influenza virus (HPAIV) subtype H5N1 is still a matter of debate. Consecutive or simultaneous infections with different subtypes of influenza viruses of low pathogenicity (LPAIV) are very common in wild duck populations. To better understand the epidemiology and pathogenesis of HPAIV H5N1 infections in natural ecosystems, we investigated the influence of prior infection of mallards with homo- (H5N2) and heterosubtypic (H4N6) LPAIV on exposure to HPAIV H5N1. In mallards with homosubtypic immunity induced by LPAIV infection, clinical disease was absent and shedding of HPAIV from respiratory and intestinal tracts was grossly reduced compared to the heterosubtypic and control groups (mean GEC/100 µl at 3 dpi: 3.0×102 vs. 2.3×104 vs. 8.7×104; p<0.05). Heterosubtypic immunity induced by an H4N6 infection mediated a similar but less pronounced effect. We conclude that the epidemiology of HPAIV H5N1 in mallards and probably other aquatic wild bird species is massively influenced by interfering immunity induced by prior homo- and heterosubtypic LPAIV infections. PMID:19693268

  9. Influenza Vaccination Generates Cytokine-Induced Memory-like NK Cells: Impact of Human Cytomegalovirus Infection

    PubMed Central

    Goodier, Martin R.; Rodriguez-Galan, Ana; Lusa, Chiara; Nielsen, Carolyn M.; Darboe, Alansana; Moldoveanu, Ana L.; White, Matthew J.; Behrens, Ron

    2016-01-01

    Human NK cells are activated by cytokines, immune complexes, and signals transduced via activating ligands on other host cells. After vaccination, or during secondary infection, adaptive immune responses can enhance both cytokine-driven and Ab-dependent NK cell responses. However, induction of NK cells for enhanced function after in vitro exposure to innate inflammatory cytokines has also been reported and may synergize with adaptive signals to potentiate NK cell activity during infection or vaccination. To test this hypothesis, we examined the effect of seasonal influenza vaccination on NK cell function and phenotype in 52 previously unvaccinated individuals. Enhanced, IL-2–dependent, NK cell IFN-γ responses to Influenza A/California/7/2009 virus were detected up to 4 wk postvaccination and higher in human CMV (HCMV)-seronegative (HCMV−) individuals than in HCMV-seropositive (HCMV+) individuals. By comparison, robust NK cell degranulation responses were observed both before and after vaccination, due to high titers of naturally occurring anti-influenza Abs in human plasma, and did not differ between HCMV+ and HCMV− subjects. In addition to these IL-2–dependent and Ab-dependent responses, NK cell responses to innate cytokines were also enhanced after influenza vaccination; this was associated with proliferation of CD57− NK cells and was most evident in HCMV+ subjects. Similar enhancement of cytokine responsiveness was observed when NK cells were cocultured in vitro with Influenza A/California/7/2009 virus, and this was at least partially dependent upon IFN-αβR2. In summary, our data indicate that attenuated or live viral vaccines promote cytokine-induced memory-like NK cells and that this process is influenced by HCMV infection. PMID:27233958

  10. Influenza Vaccination Generates Cytokine-Induced Memory-like NK Cells: Impact of Human Cytomegalovirus Infection.

    PubMed

    Goodier, Martin R; Rodriguez-Galan, Ana; Lusa, Chiara; Nielsen, Carolyn M; Darboe, Alansana; Moldoveanu, Ana L; White, Matthew J; Behrens, Ron; Riley, Eleanor M

    2016-07-01

    Human NK cells are activated by cytokines, immune complexes, and signals transduced via activating ligands on other host cells. After vaccination, or during secondary infection, adaptive immune responses can enhance both cytokine-driven and Ab-dependent NK cell responses. However, induction of NK cells for enhanced function after in vitro exposure to innate inflammatory cytokines has also been reported and may synergize with adaptive signals to potentiate NK cell activity during infection or vaccination. To test this hypothesis, we examined the effect of seasonal influenza vaccination on NK cell function and phenotype in 52 previously unvaccinated individuals. Enhanced, IL-2-dependent, NK cell IFN-γ responses to Influenza A/California/7/2009 virus were detected up to 4 wk postvaccination and higher in human CMV (HCMV)-seronegative (HCMV(-)) individuals than in HCMV-seropositive (HCMV(+)) individuals. By comparison, robust NK cell degranulation responses were observed both before and after vaccination, due to high titers of naturally occurring anti-influenza Abs in human plasma, and did not differ between HCMV(+) and HCMV(-) subjects. In addition to these IL-2-dependent and Ab-dependent responses, NK cell responses to innate cytokines were also enhanced after influenza vaccination; this was associated with proliferation of CD57(-) NK cells and was most evident in HCMV(+) subjects. Similar enhancement of cytokine responsiveness was observed when NK cells were cocultured in vitro with Influenza A/California/7/2009 virus, and this was at least partially dependent upon IFN-αβR2. In summary, our data indicate that attenuated or live viral vaccines promote cytokine-induced memory-like NK cells and that this process is influenced by HCMV infection. PMID:27233958

  11. Free-grazing Ducks and Highly Pathogenic Avian Influenza, Thailand

    PubMed Central

    Chaitaweesub, Prasit; Parakamawongsa, Tippawon; Premashthira, Sith; Tiensin, Thanawat; Kalpravidh, Wantanee; Wagner, Hans; Slingenbergh, Jan

    2006-01-01

    Thailand has recently had 3 epidemic waves of highly pathogenic avian influenza (HPAI); virus was again detected in July 2005. Risk factors need to be identified to better understand disease ecology and assist HPAI surveillance and detection. This study analyzed the spatial distribution of HPAI outbreaks in relation to poultry, land use, and other anthropogenic variables from the start of the second epidemic wave (July 2004–May 2005). Results demonstrate a strong association between H5N1 virus in Thailand and abundance of free-grazing ducks and, to a lesser extent, native chickens, cocks, wetlands, and humans. Wetlands used for double-crop rice production, where free-grazing duck feed year round in rice paddies, appear to be a critical factor in HPAI persistence and spread. This finding could be important for other duck-producing regions in eastern and southeastern Asian countries affected by HPAI. PMID:16494747

  12. Highly Pathogenic Avian Influenza H5N1, Thailand, 2004

    PubMed Central

    Chaitaweesub, Prasit; Songserm, Thaweesak; Chaisingh, Arunee; Hoonsuwan, Wirongrong; Buranathai, Chantanee; Parakamawongsa, Tippawon; Premashthira, Sith; Amonsin, Alongkorn; Gilbert, Marius; Nielen, Mirjam; Stegeman, Arjan

    2005-01-01

    In January 2004, highly pathogenic avian influenza (HPAI) virus of the H5N1 subtype was first confirmed in poultry and humans in Thailand. Control measures, e.g., culling poultry flocks, restricting poultry movement, and improving hygiene, were implemented. Poultry populations in 1,417 villages in 60 of 76 provinces were affected in 2004. A total of 83% of infected flocks confirmed by laboratories were backyard chickens (56%) or ducks (27%). Outbreaks were concentrated in the Central, the southern part of the Northern, and Eastern Regions of Thailand, which are wetlands, water reservoirs, and dense poultry areas. More than 62 million birds were either killed by HPAI viruses or culled. H5N1 virus from poultry caused 17 human cases and 12 deaths in Thailand; a number of domestic cats, captive tigers, and leopards also died of the H5N1 virus. In 2005, the epidemic is ongoing in Thailand. PMID:16318716

  13. Highly Pathogenic Avian Influenza Virus among Wild Birds in Mongolia

    PubMed Central

    Gilbert, Martin; Jambal, Losolmaa; Karesh, William B.; Fine, Amanda; Shiilegdamba, Enkhtuvshin; Dulam, Purevtseren; Sodnomdarjaa, Ruuragchaa; Ganzorig, Khuukhenbaatar; Batchuluun, Damdinjav; Tseveenmyadag, Natsagdorj; Bolortuya, Purevsuren; Cardona, Carol J.; Leung, Connie Y. H.; Peiris, J. S. Malik; Spackman, Erica; Swayne, David E.; Joly, Damien O.

    2012-01-01

    Mongolia combines a near absence of domestic poultry, with an abundance of migratory waterbirds, to create an ideal location to study the epidemiology of highly pathogenic avian influenza virus (HPAIV) in a purely wild bird system. Here we present the findings of active and passive surveillance for HPAIV subtype H5N1 in Mongolia from 2005–2011, together with the results of five outbreak investigations. In total eight HPAIV outbreaks were confirmed in Mongolia during this period. Of these, one was detected during active surveillance employed by this project, three by active surveillance performed by Mongolian government agencies, and four through passive surveillance. A further three outbreaks were recorded in the neighbouring Tyva Republic of Russia on a lake that bisects the international border. No HPAIV was isolated (cultured) from 7,855 environmental fecal samples (primarily from ducks), or from 2,765 live, clinically healthy birds captured during active surveillance (primarily shelducks, geese and swans), while four HPAIVs were isolated from 141 clinically ill or dead birds located through active surveillance. Two low pathogenic avian influenza viruses (LPAIV) were cultured from ill or dead birds during active surveillance, while environmental feces and live healthy birds yielded 56 and 1 LPAIV respectively. All Mongolian outbreaks occurred in 2005 and 2006 (clade 2.2), or 2009 and 2010 (clade 2.3.2.1); all years in which spring HPAIV outbreaks were reported in Tibet and/or Qinghai provinces in China. The occurrence of outbreaks in areas deficient in domestic poultry is strong evidence that wild birds can carry HPAIV over at least moderate distances. However, failure to detect further outbreaks of clade 2.2 after June 2006, and clade 2.3.2.1 after June 2010 suggests that wild birds migrating to and from Mongolia may not be competent as indefinite reservoirs of HPAIV, or that HPAIV did not reach susceptible populations during our study. PMID:22984464

  14. Genetic characterization of highly pathogenic H5 influenza viruses from poultry in Taiwan, 2015.

    PubMed

    Huang, Pei-Yu; Lee, Chang-Chun David; Yip, Chun-Hung; Cheung, Chung-Lam; Yu, Guangchuang; Lam, Tommy Tsan-Yuk; Smith, David K; Zhu, Huachen; Guan, Yi

    2016-03-01

    Phylogenetic analysis of the highly pathogenic avian influenza (HPAI) H5 viruses causing recent outbreaks in Taiwan showed that they belonged to the Asian HPAI H5 lineage, clade 2.3.4.4 viruses, and were apparently introduced by migratory birds. These viruses reassorted with Eurasian influenza gene pool viruses and formed five genotypic variants. As Taiwan has a similar influenza ecosystem to southern China, the HPAI H5 lineage could become established and enzootic in the island. PMID:26690663

  15. The role of vaccines and vaccination in high pathogenicity avian influenza control and eradication

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Thirty epizootics of high pathogenicity avian influenza (HPAI) have occurred in the world since influenza was identified as the etiology in 1955. Twenty-four of the epizootics were eradicated by using stamping-out programs composed of education, biosecurity, rapid diagnostics and surveillance, and ...

  16. Susceptibility of avian species to north american H13 low pathogenic avian influenza viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gulls are widely recognized reservoirs for low pathogenic avian influenza (LPAI) viruses; however, the subtypes maintained in these populations and/or the transmission mechanisms involved are poorly understood. Although, a wide diversity of influenza viruses have been isolated from gulls, two hemag...

  17. Comparative susceptibility of avian species to low pathogenic avian influenza viruses of the H13 subtype

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gulls are widely recognized reservoirs for low pathogenic avian influenza (LPAI) viruses; however, the subtypes maintained in these populations and/or the transmission mechanisms involved are poorly understood. Although, a wide diversity of influenza viruses have been isolated from gulls, two hemag...

  18. 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 ...

  19. 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...

  20. Current status and future needs in diagnostics and vaccines for high pathogenicity avian influenza

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since 1959, 31 epizootics of high pathogenicity avian influenza (HPAI) have occurred in birds. Rapid detection and accurate identification of HPAI has been critical to controlling such epizootics in poultry. Specific paradigms for the detection and diagnosis of avian influenza virus (AIV) in poultry...

  1. Susceptibility of wood ducks to H5N1 highly pathogenic avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since 2002, H5N1 highly pathogenic avian influenza (HPAI) viruses have caused mortality in numerous species of wild birds; this is atypical for avian influenza virus (AIV) infections in wild birds, especially for species in the Order Anseriformes. Although these infections document the susceptibili...

  2. Human Infection with Highly Pathogenic A(H7N7) Avian Influenza Virus, Italy, 2013

    PubMed Central

    Rossini, Giada; Facchini, Marzia; Vaccari, Gabriele; Di Trani, Livia; Di Martino, Angela; Gaibani, Paolo; Vocale, Caterina; Cattoli, Giovanni; Bennett, Michael; McCauley, John W.; Rezza, Giovanni; Moro, Maria Luisa; Rangoni, Roberto; Finarelli, Alba Carola; Landini, Maria Paola; Castrucci, Maria Rita; Donatelli, Isabella

    2014-01-01

    During an influenza A(H7N7) virus outbreak among poultry in Italy during August–September 2013, infection with a highly pathogenic A(H7N7) avian influenza virus was diagnosed for 3 poultry workers with conjunctivitis. Genetic analyses revealed that the viruses from the humans were closely related to those from chickens on affected farms. PMID:25271444

  3. Impact of poultry vaccines on control of H5N1 high pathogenicity avian influenza

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Use of vaccines against avian influenza (AI) have been sporadic in poultry until 2002 when the H5N1 high pathogenicity avian influenza (HPAI) spread from China to Hong Kong, and then multiple southeast Asian countries in 2003-2004, and to Europe in 2005, and Africa in 2006. Over the past 40 years, ...

  4. Susceptibility of Swine to Low Pathogenic H5 and H7 Avian Influenza Viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: The emergence of the 2009 pandemic H1N1 influenza virus from swine origin viruses (1) reinforced the concern about transmission of animal influenza viruses to man. This follows the transmission of highly pathogenic H5N1 viruses from birds to people identified in the late 1990s and cont...

  5. Emergence of a Highly Pathogenic Avian Influenza Virus from a Low-Pathogenic Progenitor

    PubMed Central

    Fusaro, Alice; Nelson, Martha I.; Bonfanti, Lebana; Mulatti, Paolo; Hughes, Joseph; Murcia, Pablo R.; Schivo, Alessia; Valastro, Viviana; Moreno, Ana; Holmes, Edward C.; Cattoli, Giovanni

    2014-01-01

    ABSTRACT Avian influenza (AI) viruses of the H7 subtype have the potential to evolve into highly pathogenic (HP) viruses that represent a major economic problem for the poultry industry and a threat to global health. However, the emergence of HPAI viruses from low-pathogenic (LPAI) progenitor viruses currently is poorly understood. To investigate the origin and evolution of one of the most important avian influenza epidemics described in Europe, we investigated the evolutionary and spatial dynamics of the entire genome of 109 H7N1 (46 LPAI and 63 HPAI) viruses collected during Italian H7N1 outbreaks between March 1999 and February 2001. Phylogenetic analysis revealed that the LPAI and HPAI epidemics shared a single ancestor, that the HPAI strains evolved from the LPAI viruses in the absence of reassortment, and that there was a parallel emergence of mutations among HPAI and later LPAI lineages. Notably, an ultradeep-sequencing analysis demonstrated that some of the amino acid changes characterizing the HPAI virus cluster were already present with low frequency within several individual viral populations from the beginning of the LPAI H7N1 epidemic. A Bayesian phylogeographic analysis revealed stronger spatial structure during the LPAI outbreak, reflecting the more rapid spread of the virus following the emergence of HPAI. The data generated in this study provide the most complete evolutionary and phylogeographic analysis of epidemiologically intertwined high- and low-pathogenicity viruses undertaken to date and highlight the importance of implementing prompt eradication measures against LPAI to prevent the appearance of viruses with fitness advantages and unpredictable pathogenic properties. IMPORTANCE The Italian H7 AI epidemic of 1999 to 2001 was one of the most important AI outbreaks described in Europe. H7 viruses have the ability to evolve into HP forms from LP precursors, although the mechanisms underlying this evolutionary transition are only poorly

  6. Highly pathogenic avian influenza viruses and generation of novel reassortants,United States, 2014–2015

    USGS Publications Warehouse

    Dong-Hun Lee; Justin Bahl; Mia Kim Torchetti; Mary Lea Killian; Ip, Hon S.; David E Swayne

    2016-01-01

    Asian highly pathogenic avian influenza A(H5N8) viruses spread into North America in 2014 during autumn bird migration. Complete genome sequencing and phylogenetic analysis of 32 H5 viruses identified novel H5N1, H5N2, and H5N8 viruses that emerged in late 2014 through reassortment with North American low-pathogenicity avian influenza viruses.

  7. Highly Pathogenic Avian Influenza Viruses and Generation of Novel Reassortants, United States, 2014–2015

    PubMed Central

    Lee, Dong-Hun; Bahl, Justin; Torchetti, Mia Kim; Killian, Mary Lea; Ip, Hon S.; DeLiberto, Thomas J.

    2016-01-01

    Asian highly pathogenic avian influenza A(H5N8) viruses spread into North America in 2014 during autumn bird migration. Complete genome sequencing and phylogenetic analysis of 32 H5 viruses identified novel H5N1, H5N2, and H5N8 viruses that emerged in late 2014 through reassortment with North American low-pathogenicity avian influenza viruses. PMID:27314845

  8. Highly Pathogenic Avian Influenza Viruses and Generation of Novel Reassortants, United States, 2014-2015.

    PubMed

    Lee, Dong-Hun; Bahl, Justin; Torchetti, Mia Kim; Killian, Mary Lea; Ip, Hon S; DeLiberto, Thomas J; Swayne, David E

    2016-07-01

    Asian highly pathogenic avian influenza A(H5N8) viruses spread into North America in 2014 during autumn bird migration. Complete genome sequencing and phylogenetic analysis of 32 H5 viruses identified novel H5N1, H5N2, and H5N8 viruses that emerged in late 2014 through reassortment with North American low-pathogenicity avian influenza viruses. PMID:27314845

  9. Quantifying Transmission of Highly Pathogenic and Low Pathogenicity H7N1 Avian Influenza in Turkeys

    PubMed Central

    Saenz, Roberto A.; Essen, Steve C.; Brookes, Sharon M.; Iqbal, Munir; Wood, James L. N.; Grenfell, Bryan T.; McCauley, John W.; Brown, Ian H.; Gog, Julia R.

    2012-01-01

    Outbreaks of avian influenza in poultry can be devastating, yet many of the basic epidemiological parameters have not been accurately characterised. In 1999–2000 in Northern Italy, outbreaks of H7N1 low pathogenicity avian influenza virus (LPAI) were followed by the emergence of H7N1 highly pathogenic avian influenza virus (HPAI). This study investigates the transmission dynamics in turkeys of representative HPAI and LPAI H7N1 virus strains from this outbreak in an experimental setting, allowing direct comparison of the two strains. The fitted transmission rates for the two strains are similar: 2.04 (1.5–2.7) per day for HPAI, 2.01 (1.6–2.5) per day for LPAI. However, the mean infectious period is far shorter for HPAI (1.47 (1.3–1.7) days) than for LPAI (7.65 (7.0–8.3) days), due to the rapid death of infected turkeys. Hence the basic reproductive ratio, is significantly lower for HPAI (3.01 (2.2–4.0)) than for LPAI (15.3 (11.8–19.7)). The comparison of transmission rates and are critically important in relation to understanding how HPAI might emerge from LPAI. Two competing hypotheses for how transmission rates vary with population size are tested by fitting competing models to experiments with differing numbers of turkeys. A model with frequency-dependent transmission gives a significantly better fit to experimental data than density-dependent transmission. This has important implications for extrapolating experimental results from relatively small numbers of birds to the commercial poultry flock size, and for how control, including vaccination, might scale with flock size. PMID:23028760

  10. Animal cytomegaloviruses.

    PubMed Central

    Staczek, J

    1990-01-01

    Cytomegaloviruses are agents that infect a variety of animals. Human cytomegalovirus is associated with infections that may be inapparent or may result in severe body malformation. More recently, human cytomegalovirus infections have been recognized as causing severe complications in immunosuppressed individuals. In other animals, cytomegaloviruses are often associated with infections having relatively mild sequelae. Many of these sequelae parallel symptoms associated with human cytomegalovirus infections. Recent advances in biotechnology have permitted the study of many of the animal cytomegaloviruses in vitro. Consequently, animal cytomegaloviruses can be used as model systems for studying the pathogenesis, immunobiology, and molecular biology of cytomegalovirus-host and cytomegalovirus-cell interactions. PMID:2170830

  11. Control strategies for highly pathogenic avian influenza: a global perspective.

    PubMed

    Lubroth, J

    2007-01-01

    Comprehensive programmes for the prevention, detection and control of highly pathogenic avian influenza (HPAI) require a national dimension and relevant national legislation in which veterinary services can conduct surveillance, competent diagnosis and rapid response. Avian influenza was controlled and prevented by vaccination long before the current H5N1 crisis. The use of vaccine cannot be separated from other essential elements of a vaccination campaign, which include education in poultry production practices, such as hygiene, all in-all out production concepts, separation of species, biosecurity (bio-exclusion to keep the disease out and biocontainment to keep the disease from spreading once suspected or detected), competence in giving the vaccine and the role of vaccination teams, post-vaccination monitoring to ensure efficacy and to detect the circulation of wild-type virus, surveillance and buffer zones in outbreak areas, and performance indicators to determine when vaccination can cease. Reporting of disease can be improved through well-structured, adequately financed veterinary services and also by fair compensation for producers who suffer financial loss. A rapid response to suspected cases of HPAI should be ensured in simulation exercises involving various sectors of the food production and marketing chain, policy-makers, official veterinary structures and other government personnel. As for other transboundary animal diseases, national approaches must be part of a regional strategy and regional networks for cooperation and information sharing, which in turn reflect global policies and international standards, such as the quality of vaccines, reporting obligations, humane interventions, cleaning and disinfection methods, restocking times, monitoring and safe trade. PMID:18411931

  12. A Homolog Pentameric Complex Dictates Viral Epithelial Tropism, Pathogenicity and Congenital Infection Rate in Guinea Pig Cytomegalovirus.

    PubMed

    Coleman, Stewart; Choi, K Yeon; Root, Matthew; McGregor, Alistair

    2016-07-01

    In human cytomegalovirus (HCMV), tropism to epithelial and endothelial cells is dependent upon a pentameric complex (PC). Given the structure of the placenta, the PC is potentially an important neutralizing antibody target antigen against congenital infection. The guinea pig is the only small animal model for congenital CMV. Guinea pig cytomegalovirus (GPCMV) potentially encodes a UL128-131 HCMV PC homolog locus (GP128-GP133). In transient expression studies, GPCMV gH and gL glycoproteins interacted with UL128, UL130 and UL131 homolog proteins (designated GP129 and GP131 and GP133 respectively) to form PC or subcomplexes which were determined by immunoprecipitation reactions directed to gH or gL. A natural GP129 C-terminal deletion mutant (aa 107-179) and a chimeric HCMV UL128 C-terminal domain swap GP129 mutant failed to form PC with other components. GPCMV infection of a newly established guinea pig epithelial cell line required a complete PC and a GP129 mutant virus lacked epithelial tropism and was attenuated in the guinea pig for pathogenicity and had a low congenital transmission rate. Individual knockout of GP131 or 133 genes resulted in loss of viral epithelial tropism. A GP128 mutant virus retained epithelial tropism and GP128 was determined not to be a PC component. A series of GPCMV mutants demonstrated that gO was not strictly essential for epithelial infection whereas gB and the PC were essential. Ectopic expression of a GP129 cDNA in a GP129 mutant virus restored epithelial tropism, pathogenicity and congenital infection. Overall, GPCMV forms a PC similar to HCMV which enables evaluation of PC based vaccine strategies in the guinea pig model. PMID:27387220

  13. A Homolog Pentameric Complex Dictates Viral Epithelial Tropism, Pathogenicity and Congenital Infection Rate in Guinea Pig Cytomegalovirus

    PubMed Central

    McGregor, Alistair

    2016-01-01

    In human cytomegalovirus (HCMV), tropism to epithelial and endothelial cells is dependent upon a pentameric complex (PC). Given the structure of the placenta, the PC is potentially an important neutralizing antibody target antigen against congenital infection. The guinea pig is the only small animal model for congenital CMV. Guinea pig cytomegalovirus (GPCMV) potentially encodes a UL128-131 HCMV PC homolog locus (GP128-GP133). In transient expression studies, GPCMV gH and gL glycoproteins interacted with UL128, UL130 and UL131 homolog proteins (designated GP129 and GP131 and GP133 respectively) to form PC or subcomplexes which were determined by immunoprecipitation reactions directed to gH or gL. A natural GP129 C-terminal deletion mutant (aa 107–179) and a chimeric HCMV UL128 C-terminal domain swap GP129 mutant failed to form PC with other components. GPCMV infection of a newly established guinea pig epithelial cell line required a complete PC and a GP129 mutant virus lacked epithelial tropism and was attenuated in the guinea pig for pathogenicity and had a low congenital transmission rate. Individual knockout of GP131 or 133 genes resulted in loss of viral epithelial tropism. A GP128 mutant virus retained epithelial tropism and GP128 was determined not to be a PC component. A series of GPCMV mutants demonstrated that gO was not strictly essential for epithelial infection whereas gB and the PC were essential. Ectopic expression of a GP129 cDNA in a GP129 mutant virus restored epithelial tropism, pathogenicity and congenital infection. Overall, GPCMV forms a PC similar to HCMV which enables evaluation of PC based vaccine strategies in the guinea pig model. PMID:27387220

  14. Assessment of national strategies for control of high pathogenicity avian influenza and low pathogenicity notifiable avian influenza in poultry, with emphasis on vaccines and vaccination

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Twenty-nine distinct epizootics of highly pathogenic avian influenza (HPAI) have occurred since 1959. The H5N1 HPAI panzootic affecting Asia, Africa and Eastern Europe has been the largest among these, affecting poultry and/or wild birds in 63 countries. Historically, control strategies have focus...

  15. Increased virulence in ducks of H5N1 highly pathogenic avian influenza viruses from Egypt

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The pathogenicity of H5N1 highly pathogenic avian influenza (HPAI) viruses in domestic ducks has increased over time. These changes in virulence have been reported with viruses from countries with high population of domestic ducks. Since 2006, H5N1 HPAI outbreaks in Egypt have been occurring in po...

  16. 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 ...

  17. Age at infection affects the pathogenicity of Asian highly pathogenic avian influenza H5N1 viruses in ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Asian H5N1 avian influenza (AI) viruses have changed from producing no disease or mild respiratory infections in ducks to some strains causing systemic disease and death. Differences in pathogenicity between four of these viruses as well as the effect of host age on the outcome of infection were...

  18. Potential strategies and biosafety protocols used for dual-use research on highly pathogenic influenza viruses

    PubMed Central

    Du, Lanying; Li, Ye; Gao, Jimin; Zhou, Yusen; Jiang, Shibo

    2013-01-01

    Summary Influenza A viruses (IAVs), particularly the highly pathogenic avian influenza (HPAI) H5N1, have posed a substantial threat to public health worldwide. Although the laboratory generation of the mutant influenza virus H5N1 with airborne transmissibility among mammals, which has been considered as a dual-use research, may benefit the development of effective vaccines and therapeutics against the emerging infectious agents, it may also pose threats to national biosecurity, laboratory biosafety, and/or public health. This review introduces the classification and characterization of IAVs, pinpoints historic pandemics and epidemics caused by IAVs, emphasizes the significance and necessity of biosafety, summarizes currently established biosafety-related protocols for IAV research, and provides potential strategies to improve biosafety protocols for dual-use research on the highly pathogenic avian influenza viruses and other emerging infectious agents. PMID:22987727

  19. Highly pathogenic avian influenza virus (H5N1) in experimentally infected adult mute swans.

    PubMed

    Kalthoff, Donata; Breithaupt, Angele; Teifke, Jens P; Globig, Anja; Harder, Timm; Mettenleiter, Thomas C; Beer, Martin

    2008-08-01

    Adult, healthy mute swans were experimentally infected with highly pathogenic avian influenza virus A/Cygnus cygnus/Germany/R65/2006 subtype H5N1. Immunologically naive birds died, whereas animals with preexisting, naturally acquired avian influenza virus-specific antibodies became infected asymptomatically and shed virus. Adult mute swans are highly susceptible, excrete virus, and can be clinically protected by preexposure immunity. PMID:18680652

  20. Single vaccination provides limited protection to ducks and geese against H5N1 high pathogenicity avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since 2002, high pathogenicity avian influenza has spread from Asia to Europe and into Africa causing the largest epizootic of high pathogenicity avian influenza (HPAI) of the last 50 years including infecting domestic and wild waterfowl. Our study was conducted to investigate whether single vaccina...

  1. Survivability of Eurasian H5N1 highly pathogenic avian influenza viruses in water varies between strains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aquatic habitats play critical role in the transmission and maintenance of low pathogenic avian influenza (LPAI) viruses in wild waterfowl; however the importance of these environments in the ecology of H5N1 highly pathogenic avian influenza (HPAI) viruses is unknown. In laboratory-based studies, L...

  2. 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 ...

  3. The Transcription and Translation Landscapes during Human Cytomegalovirus Infection Reveal Novel Host-Pathogen Interactions.

    PubMed

    Tirosh, Osnat; Cohen, Yifat; Shitrit, Alina; Shani, Odem; Le-Trilling, Vu Thuy Khanh; Trilling, Mirko; Friedlander, Gilgi; Tanenbaum, Marvin; Stern-Ginossar, Noam

    2015-01-01

    Viruses are by definition fully dependent on the cellular translation machinery, and develop diverse mechanisms to co-opt this machinery for their own benefit. Unlike many viruses, human cytomegalovirus (HCMV) does suppress the host translation machinery, and the extent to which translation machinery contributes to the overall pattern of viral replication and pathogenesis remains elusive. Here, we combine RNA sequencing and ribosomal profiling analyses to systematically address this question. By simultaneously examining the changes in transcription and translation along HCMV infection, we uncover extensive transcriptional control that dominates the response to infection, but also diverse and dynamic translational regulation for subsets of host genes. We were also able to show that, at late time points in infection, translation of viral mRNAs is higher than that of cellular mRNAs. Lastly, integration of our translation measurements with recent measurements of protein abundance enabled comprehensive identification of dozens of host proteins that are targeted for degradation during HCMV infection. Since targeted degradation indicates a strong biological importance, this approach should be applicable for discovering central host functions during viral infection. Our work provides a framework for studying the contribution of transcription, translation and degradation during infection with any virus. PMID:26599541

  4. The Transcription and Translation Landscapes during Human Cytomegalovirus Infection Reveal Novel Host-Pathogen Interactions

    PubMed Central

    Shitrit, Alina; Shani, Odem; Le-Trilling, Vu Thuy Khanh; Trilling, Mirko; Friedlander, Gilgi; Tanenbaum, Marvin; Stern-Ginossar, Noam

    2015-01-01

    Viruses are by definition fully dependent on the cellular translation machinery, and develop diverse mechanisms to co-opt this machinery for their own benefit. Unlike many viruses, human cytomegalovirus (HCMV) does suppress the host translation machinery, and the extent to which translation machinery contributes to the overall pattern of viral replication and pathogenesis remains elusive. Here, we combine RNA sequencing and ribosomal profiling analyses to systematically address this question. By simultaneously examining the changes in transcription and translation along HCMV infection, we uncover extensive transcriptional control that dominates the response to infection, but also diverse and dynamic translational regulation for subsets of host genes. We were also able to show that, at late time points in infection, translation of viral mRNAs is higher than that of cellular mRNAs. Lastly, integration of our translation measurements with recent measurements of protein abundance enabled comprehensive identification of dozens of host proteins that are targeted for degradation during HCMV infection. Since targeted degradation indicates a strong biological importance, this approach should be applicable for discovering central host functions during viral infection. Our work provides a framework for studying the contribution of transcription, translation and degradation during infection with any virus. PMID:26599541

  5. Multiple introductions of highly pathogenic avian influenza H5N1 viruses into Bangladesh

    PubMed Central

    Marinova-Petkova, Atanaska; Feeroz, Mohammed M; Rabiul Alam, SM; Kamrul Hasan, M; Akhtar, Sharmin; Jones-Engel, Lisa; Walker, David; McClenaghan, Laura; Rubrum, Adam; Franks, John; Seiler, Patrick; Jeevan, Trushar; McKenzie, Pamela; Krauss, Scott; Webby, Richard J; Webster, Robert G

    2014-01-01

    Highly pathogenic H5N1 and low pathogenic H9N2 influenza viruses are endemic to poultry markets in Bangladesh and have cocirculated since 2008. H9N2 influenza viruses circulated constantly in the poultry markets, whereas highly pathogenic H5N1 viruses occurred sporadically, with peaks of activity in cooler months. Thirty highly pathogenic H5N1 influenza viruses isolated from poultry were characterized by antigenic, molecular, and phylogenetic analyses. Highly pathogenic H5N1 influenza viruses from clades 2.2.2 and 2.3.2.1 were isolated from live bird markets only. Phylogenetic analysis of the 30 H5N1 isolates revealed multiple introductions of H5N1 influenza viruses in Bangladesh. There was no reassortment between the local H9N2 influenza viruses and H5N1 genotype, despite their prolonged cocirculation. However, we detected two reassortant H5N1 viruses, carrying the M gene from the Chinese H9N2 lineage, which briefly circulated in the Bangladesh poultry markets and then disappeared. On the other hand, interclade reassortment occurred within H5N1 lineages and played a role in the genesis of the currently dominant H5N1 viruses in Bangladesh. Few ‘human-like' mutations in H5N1 may account for the limited number of human cases. Antigenically, clade 2.3.2.1 H5N1 viruses in Bangladesh have evolved since their introduction and are currently mainly homogenous, and show evidence of recent antigenic drift. Although reassortants containing H9N2 genes were detected in live poultry markets in Bangladesh, these reassortants failed to supplant the dominant H5N1 lineage. PMID:26038508

  6. 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...

  7. Within-Host Models of High and Low Pathogenic Influenza Virus Infections: The Role of Macrophages.

    PubMed

    Pawelek, Kasia A; Dor, Daniel; Salmeron, Cristian; Handel, Andreas

    2016-01-01

    The World Health Organization identifies influenza as a major public health problem. While the strains commonly circulating in humans usually do not cause severe pathogenicity in healthy adults, some strains that have infected humans, such as H5N1, can cause high morbidity and mortality. Based on the severity of the disease, influenza viruses are sometimes categorized as either being highly pathogenic (HP) or having low pathogenicity (LP). The reasons why some strains are LP and others HP are not fully understood. While there are likely multiple mechanisms of interaction between the virus and the immune response that determine LP versus HP outcomes, we focus here on one component, namely macrophages (MP). There is some evidence that MP may both help fight the infection and become productively infected with HP influenza viruses. We developed mathematical models for influenza infections which explicitly included the dynamics and action of MP. We fit these models to viral load and macrophage count data from experimental infections of mice with LP and HP strains. Our results suggest that MP may not only help fight an influenza infection but may contribute to virus production in infections with HP viruses. We also explored the impact of combination therapies with antivirals and anti-inflammatory drugs on HP infections. Our study suggests a possible mechanism of MP in determining HP versus LP outcomes, and how different interventions might affect infection dynamics. PMID:26918620

  8. Within-Host Models of High and Low Pathogenic Influenza Virus Infections: The Role of Macrophages

    PubMed Central

    Pawelek, Kasia A.; Dor, Daniel; Salmeron, Cristian; Handel, Andreas

    2016-01-01

    The World Health Organization identifies influenza as a major public health problem. While the strains commonly circulating in humans usually do not cause severe pathogenicity in healthy adults, some strains that have infected humans, such as H5N1, can cause high morbidity and mortality. Based on the severity of the disease, influenza viruses are sometimes categorized as either being highly pathogenic (HP) or having low pathogenicity (LP). The reasons why some strains are LP and others HP are not fully understood. While there are likely multiple mechanisms of interaction between the virus and the immune response that determine LP versus HP outcomes, we focus here on one component, namely macrophages (MP). There is some evidence that MP may both help fight the infection and become productively infected with HP influenza viruses. We developed mathematical models for influenza infections which explicitly included the dynamics and action of MP. We fit these models to viral load and macrophage count data from experimental infections of mice with LP and HP strains. Our results suggest that MP may not only help fight an influenza infection but may contribute to virus production in infections with HP viruses. We also explored the impact of combination therapies with antivirals and anti-inflammatory drugs on HP infections. Our study suggests a possible mechanism of MP in determining HP versus LP outcomes, and how different interventions might affect infection dynamics. PMID:26918620

  9. Pathogenic influenza B virus in the ferret model establishes lower respiratory tract infection

    PubMed Central

    Huang, Stephen S. H.; Banner, David; Paquette, Stephane G.; Leon, Alberto J.; Kelvin, Alyson A.

    2014-01-01

    Influenza B viruses have become increasingly more prominent during influenza seasons. Influenza B infection is typically considered a mild disease and receives less attention than influenza A, but has been causing 20 to 50 % of the total influenza incidence in several regions around the world. Although there is increasing evidence of mid to lower respiratory tract diseases such as bronchitis and pneumonia in influenza B patients, little is known about the pathogenesis of recent influenza B viruses. Here we investigated the clinical and pathological profiles of infection with strains representing the two current co-circulating B lineages (B/Yamagata and B/Victoria) in the ferret model. Specifically, we studied two B/Victoria (B/Brisbane/60/2008 and B/Bolivia/1526/2010) and two B/Yamagata (B/Florida/04/2006 and B/Wisconsin/01/2010) strain infections in ferrets and observed strain-specific but not lineage-specific pathogenicity. We found B/Brisbane/60/2008 caused the most severe clinical illness and B/Brisbane/60/2008 and the B/Yamagata strains instigated pathology in the middle to lower respiratory tract. Importantly, B/Brisbane/60/2008 established efficient lower respiratory tract infection with high viral burden. Our phylogenetic analyses demonstrate profound reassortment among recent influenza B viruses, which indicates the genetic make-up of B/Brisbane/60/2008 differs from the other strains. This may explain the pathogenicity difference post-infection in ferrets. PMID:24989173

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

    USGS Publications Warehouse

    Ip, Hon S.; Torchetti, Mia Kim; 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.

  11. 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...

  12. 9 CFR 145.15 - Diagnostic surveillance program for low pathogenic avian influenza.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Diagnostic surveillance program for low pathogenic avian influenza. 145.15 Section 145.15 Animals and Animal Products ANIMAL AND PLANT... antigen detection test. Memoranda of understanding or other means must be used to establish testing...

  13. 9 CFR 145.15 - Diagnostic surveillance program for low pathogenic avian influenza.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Diagnostic surveillance program for low pathogenic avian influenza. 145.15 Section 145.15 Animals and Animal Products ANIMAL AND PLANT... antigen detection test. Memoranda of understanding or other means must be used to establish testing...

  14. 9 CFR 145.15 - Diagnostic surveillance program for low pathogenic avian influenza.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Diagnostic surveillance program for low pathogenic avian influenza. 145.15 Section 145.15 Animals and Animal Products ANIMAL AND PLANT... antigen detection test. Memoranda of understanding or other means must be used to establish testing...

  15. 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...

  16. Global expansion of high pathogenicity avian influenza: implications on prevention and control programs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The H5N1 high pathogenicity avian influenza (HPAI) virus emerged in China during 1996 and has spread to infect poultry and/or wild birds in 63 countries during the past 18 years. The majority of the recent outbreaks of H5N1 HPAI have occurred in Indonesia, Egypt, Vietnam, and Bangladesh, in decreas...

  17. Global expansion of high pathogenicity avian influenza: implications on prevention and control programs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The H5N1 high pathogenicity avian influenza (HPAI) virus emerged in China during 1996 and has spread to infect poultry and/or wild birds in 63 countries during the past 18 years. The majority of the recent outbreaks of H5N1 HPAI have occurred in Indonesia, Egypt, Vietnam, and Bangladesh, in decreasi...

  18. Thermal inactivation of high pathogenicity avian influenza viruses in chicken meat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High pathogenicity avian influenza (HPAI) viruses cause severe disease with high mortality in chickens and related gallinaceous poultry. Some HPAI viruses cause systemic infections and replicate to high titers in skeletal muscle fibers. To prevent transmission of these viruses through contaminate...

  19. H9N2 low pathogenic avian influenza in Pakistan (2012-2015)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Significant economic losses from deaths and decreased egg production have resulted from H9N2 low pathogenic avian influenza virus (LPAIV) infections in poultry across North Africa, the Middle East and Asia. The H9N2 LPAIVs have been endemic in Pakistani poultry since 1996, but no new viruses have be...

  20. 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...

  1. Low pathogenicity notifiable avian influenza (LPNAI) with an emphasis on vaccination programs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There have been 30 epizootics of H5 or H7 high pathogenicity avian influenza (HPAI) from 1959 to early 2012. The largest has been the H5N1 HPAI which began in Guangdong China in 1996, and has affected over 250 million poultry and/or wild birds in 63 countries. For most countries, stamping-out prog...

  2. The pathogenicity of H7 subtype avian influenza viruses in chickens, turkeys and ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza (AI) viruses infect numerous avian species, and low pathogenicity (LP) AI viruses of the H7 subtype are typically reported to produce mild or subclinical infections in both wild aquatic birds and domestic poultry. However relatively little work has been done to compare LPAI viruses ...

  3. Chlorine inactivation of H5N1 highly pathogenic avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two Asian strains of H5N1 highly pathogenic avian influenza virus were studied to determine their resistance to chlorination. Experiments were conducted at two pH levels (pH 7 and 8) at 5 C. CT (chlorine concentration x exposure time) values were calculated for different levels of inactivation. R...

  4. Serum and egg yolk antibody detection in chickens infected with low pathogenicity avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Surveillance for low pathogenicity avian influenza virus (LPAIV) infections has primarily relied on labor intensive collection and serological testing of serum, but for many poultry diseases, easier to collect yolk samples have replaced serum for surveillance testing. A time course LPAIV infection s...

  5. 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 ...

  6. Global assessments of high pathogenicity avian influenza control, including vaccination programs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There have been 32 epizootics of H5 or H7 high pathogenicity avian influenza (HPAI) from 1959 to early 2013. The largest has been the H5N1 HPAI which began in Guangdong China in 1996, and has affected over 250 million poultry and/or wild birds in 63 countries. For most countries, stamping-out progra...

  7. 9 CFR 145.15 - Diagnostic surveillance program for low pathogenic avian influenza.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE LIVESTOCK IMPROVEMENT NATIONAL POULTRY IMPROVEMENT PLAN FOR BREEDING POULTRY General Provisions § 145.15 Diagnostic surveillance program for low... H5/H7 low pathogenic avian influenza for all poultry in the State. The exact provisions of...

  8. 9 CFR 145.15 - Diagnostic surveillance program for low pathogenic avian influenza.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE LIVESTOCK IMPROVEMENT NATIONAL POULTRY IMPROVEMENT PLAN FOR BREEDING POULTRY General Provisions § 145.15 Diagnostic surveillance program for low... H5/H7 low pathogenic avian influenza for all poultry in the State. The exact provisions of...

  9. Highly pathogenic avian influenza virus and generation of novel reassortants, United States, 2014-2015

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Asian highly pathogenic avian influenza A(H5N8) viruses spread into North America in 2014 during autumn bird migration. Complete genome sequencing and phylogenetic analysis of 32 H5 viruses identified novel H5N1, H5N2, and H5N8 viruses that emerged in late 2014 through reassortment with North Americ...

  10. 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...

  11. Susceptibility of wood ducks (Aix sponsa) to H5N1 highly pathogenic avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since 2002, H5N1 highly pathogenic avian influenza (HPAI) viruses have caused mortality in numerous species of wild birds. Although these infections document the susceptibility of wild birds to H5N1 HPAI viruses and the spillover of these viruses from infected domestic birds to wild birds, it is un...

  12. 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...

  13. Update on H7N3 highly pathogenic avian influenza in Mexico

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In June of 2012, an H7N3 highly pathogenic avian influenza (HPAI) virus was identified as the cause of a severe disease outbreak in commercial laying chicken farms in Jalisco, Mexico. This region is responsible for approximately 55% of the eggs produced in Mexico, and infection with this virus seve...

  14. 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...

  15. Novel Eurasian Highly Pathogenic Avian Influenza A H5 Viruses in Wild Birds, Washington, USA, 2014

    PubMed Central

    Ip, Hon S.; 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.

    2015-01-01

    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. PMID:25898265

  16. Cytomegalovirus retinitis

    MedlinePlus

    ... to prevent its return. Alternative Names Cytomegalovirus retinitis Images Eye CMV retinitis CMV (cytomegalovirus) References Crumpacker CS. ... 5. Read More Antibody HIV/AIDS Immune response Retinal detachment Systemic WBC count Update Date 12/10/ ...

  17. The influence of economic indicators, poultry density and the performance of Veterinary Services on the control of high-pathogenicity avian influenza in poultry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High pathogenicity avian influenza (HPAI) and low pathogenicity notifiable avian influenza (LPNAI) in poultry are notifiable to World Organisation for Animal Health (OIE) by its member countries. There may be variation between countries’ responses to avian influenza (AI) outbreak situations based o...

  18. Highly Pathogenic Avian Influenza Virus (H5N1) Outbreak in Captive Wild Birds and Cats, Cambodia

    PubMed Central

    Marx, Nick; Ong, Sivuth; Gaidet, Nicolas; Hunt, Matt; Manuguerra, Jean-Claude; Sorn, San; Peiris, Malik; Van der Werf, Sylvie; Reynes, Jean-Marc

    2009-01-01

    From December 2003 through January 2004, the Phnom Tamao Wildlife Rescue Centre, Cambodia, was affected by the highly pathogenic influenza virus (H5N1). Birds from 26 species died. Influenza virus subtype H5N1 was detected in 6 of 7 species tested. Cats from 5 of 7 species were probably infected; none died. PMID:19239769

  19. 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...

  20. Characteristics of diagnostic tests used in the 2002 low pathogenicity avian influenza H7N2 outbreak in Virginia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An outbreak of low pathogenicity avian influenza (LPAI) H7N2 occurred in 2002 in the Shenandoah Valley, Virginia, a high density poultry production region. A combination of clinical signs, and laboratory diagnostic tests designed to detect avian influenza (AI) antibodies, virus, or H7 specific RNA ...

  1. 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...

  2. Highly pathogenic H5N1 avian influenza viruses differentially affect gene expression in primary chicken embryo fibroblasts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Highly pathogenic avian influenza viruses cause severe clinical disease associated with high mortality in chickens and other gallinaceous species. However, the mechanism by which different strains of avian influenza viruses overcome host response in birds is still unclear. In the present study, ch...

  3. Pathogenicity of recombinant H5N1 avian influenza viruses with truncated NS1 gene in chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The NS1 protein of influenza A virus plays an important role in blocking the induction of type I interferon and other regulatory functions in infected cells. However, differences in length of the NS1 protein has been observed in highly pathogenic H5N1, H5N2, and H7N1 subtype avian influenza viruses...

  4. Influenza virus pathogenicity regulated by host cellular proteases, cytokines and metabolites, and its therapeutic options

    PubMed Central

    KIDO, Hiroshi

    2015-01-01

    Influenza A virus (IAV) causes significant morbidity and mortality. The knowledge gained within the last decade on the pandemic IAV(H1N1)2009 improved our understanding not only of the viral pathogenicity but also the host cellular factors involved in the pathogenicity of multiorgan failure (MOF), such as cellular trypsin-type hemagglutinin (HA0) processing proteases for viral multiplication, cytokine storm, metabolic disorders and energy crisis. The HA processing proteases in the airway and organs for all IAV known to date have been identified. Recently, a new concept on the pathogenicity of MOF, the “influenza virus–cytokine–trypsin” cycle, has been proposed involving up-regulation of trypsin through pro-inflammatory cytokines, and potentiation of viral multiplication in various organs. Furthermore, the relationship between causative factors has been summarized as the “influenza virus–cytokine–trypsin” cycle interconnected with the “metabolic disorders–cytokine” cycle. These cycles provide new treatment concepts for ATP crisis and MOF. This review discusses IAV pathogenicity on cellular proteases, cytokines, metabolites and therapeutic options. PMID:26460316

  5. 1918 and 2009 H1N1 influenza viruses are not pathogenic in birds.

    PubMed

    Babiuk, Shawn; Albrecht, Randy; Berhane, Yohannes; Marszal, Peter; Richt, Jürgen A; García-Sastre, Adolfo; Pasick, John; Weingartl, Hana

    2010-02-01

    The susceptibility of chickens to both 1918 and 2009 H1N1 influenza virus was evaluated. The intravenous pathogenicity index of 1918 and 2009 H1N1 viruses in chickens was 0. Chickens did not develop clinical signs following experimental inoculation simulating natural infection. No gross pathological changes were observed in any tissues of chickens between 2 and 18 days post-infection (p.i.) and viral RNA was not detected by real-time RT-PCR in mucosal secretions or tissues. Seroconversion was not detected in any of the chickens following inoculation with H1N1 2009 virus, whereas half the chickens developed influenza-specific antibodies at 28 days p.i. with 1918 influenza, suggesting limited infection. Viral RNA was detected by real-time RT-PCR in mallard ducks following inoculation with 1918 influenza virus at 3 days p.i. in cloacal swabs, but not in tissues, and all ducks seroconverted by 28 days p.i. Both 1918 and 2009 H1N1 influenza viruses behave as LPAI in gallinaceous poultry. PMID:19889930

  6. Wild bird surveillance for highly pathogenic avian influenza H5 in North America

    USGS Publications Warehouse

    Flint, Paul L.; Pearce, John M.; Franson, J. Christian; Derksen, Dirk V.

    2015-01-01

    It is unknown how the current Asian origin highly pathogenic avian influenza H5 viruses arrived, but these viruses are now poised to become endemic in North America. Wild birds harbor these viruses and have dispersed them at regional scales. What is unclear is how the viruses may be moving from the wild bird reservoir into poultry holdings. Active surveillance of live wild birds is likely the best way to determine the true distribution of these viruses. We also suggest that sampling be focused on regions with the greatest risk for poultry losses and attempt to define the mechanisms of transfer to enhance biosecurity. Responding to the recent outbreaks of highly pathogenic avian influenza in North America requires an efficient plan with clear objectives and potential management outcomes.

  7. Implementing hospital-based surveillance for severe acute respiratory infections caused by influenza and other respiratory pathogens in New Zealand

    PubMed Central

    Baker, Michael; McArthur, Colin; Roberts, Sally; Williamson, Deborah; Grant, Cameron; Trenholme, Adrian; Wong, Conroy; Taylor, Susan; LeComte, Lyndsay; Mackereth, Graham; Bandaranayake, Don; Wood, Tim; Bissielo, Ange; Se, Ruth; Turner, Nikki; Pierse, Nevil; Thomas, Paul; Webby, Richard; Gross, Diane; Duque, Jazmin; Thompson, Mark; Widdowson, Marc-Alain

    2014-01-01

    Background Recent experience with pandemic influenza A(H1N1)pdm09 highlighted the importance of global surveillance for severe respiratory disease to support pandemic preparedness and seasonal influenza control. Improved surveillance in the southern hemisphere is needed to provide critical data on influenza epidemiology, disease burden, circulating strains and effectiveness of influenza prevention and control measures. Hospital-based surveillance for severe acute respiratory infection (SARI) cases was established in New Zealand on 30 April 2012. The aims were to measure incidence, prevalence, risk factors, clinical spectrum and outcomes for SARI and associated influenza and other respiratory pathogen cases as well as to understand influenza contribution to patients not meeting SARI case definition. Methods/Design All inpatients with suspected respiratory infections who were admitted overnight to the study hospitals were screened daily. If a patient met the World Health Organization’s SARI case definition, a respiratory specimen was tested for influenza and other respiratory pathogens. A case report form captured demographics, history of presenting illness, co-morbidities, disease course and outcome and risk factors. These data were supplemented from electronic clinical records and other linked data sources. Discussion Hospital-based SARI surveillance has been implemented and is fully functioning in New Zealand. Active, prospective, continuous, hospital-based SARI surveillance is useful in supporting pandemic preparedness for emerging influenza A(H7N9) virus infections and seasonal influenza prevention and control. PMID:25077034

  8. Dynamics of low and high pathogenic avian influenza in wild and domestic bird populations.

    PubMed

    Tuncer, Necibe; Torres, Juan; Martcheva, Maia; Barfield, Michael; Holt, Robert D

    2016-01-01

    This paper introduces a time-since-recovery structured, multi-strain, multi-population model of avian influenza. Influenza A viruses infect many species of wild and domestic birds and are classified into two groups based on their ability to cause disease: low pathogenic avian influenza (LPAI) and high pathogenic avian influenza (HPAI). Prior infection with LPAI provides partial immunity towards HPAI. The model introduced in this paper structures LPAI-recovered birds (wild and domestic) with time-since-recovery and includes cross-immunity towards HPAI that can fade with time. The model has a unique disease-free equilibrium (DFE), unique LPAI-only and HPAI-only equilibria and at least one coexistence equilibrium. We compute the reproduction numbers of LPAI ([Formula: see text]) and HPAI ([Formula: see text]) and show that the DFE is locally asymptotically stable when [Formula: see text] and [Formula: see text]. A unique LPAI-only (HPAI-only) equilibrium exists when [Formula: see text] ([Formula: see text]) and it is locally asymptotically stable if HPAI (LPAI) cannot invade the equilibrium, that is, if the invasion number [Formula: see text] ([Formula: see text]). We show using numerical simulations that the ODE version of the model, which is obtained by discarding the time-since-recovery structures (making cross-immunity constant), can exhibit oscillations, and also that the pathogens LPAI and HPAI can coexist with sustained oscillations in both populations. Through simulations, we show that even if both populations (wild and domestic) are sinks when alone, LPAI and HPAI can persist in both populations combined. Thus, reducing the reproduction numbers of LPAI and HPAI in each population to below unity is not enough to eradicate the disease. The pathogens can continue to coexist in both populations unless transmission between the populations is reduced. PMID:26667351

  9. 75 FR 10645 - Low Pathogenic Avian Influenza; Voluntary Control Program and Payment of Indemnity

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-09

    ...We are adopting as a final rule, with changes, an interim rule that amended the regulations by establishing, under the auspices of the National Poultry Improvement Plan, a voluntary program for the control of the H5/H7 subtypes of low pathogenic avian influenza in commercial poultry. As amended by this document, the rule provides that the amount of indemnity for which contract growers are......

  10. Homo- and Heterosubtypic Low Pathogenic Avian Influenza Exposure on H5N1 Highly Pathogenic Avian Influenza Virus Infection in Wood Ducks (Aix sponsa)

    PubMed Central

    Costa, Taiana P.; Brown, Justin D.; Howerth, Elizabeth W.; Stallknecht, David E.; Swayne, David E.

    2011-01-01

    Wild birds in the Orders Anseriformes and Charadriiformes are the natural reservoirs for avian influenza (AI) viruses. Although they are often infected with multiple AI viruses, the significance and extent of acquired immunity in these populations is not understood. Pre-existing immunity to AI virus has been shown to modulate the outcome of a highly pathogenic avian influenza (HPAI) virus infection in multiple domestic avian species, but few studies have addressed this effect in wild birds. In this study, the effect of pre-exposure to homosubtypic (homologous hemagglutinin) and heterosubtypic (heterologous hemagglutinin) low pathogenic avian influenza (LPAI) viruses on the outcome of a H5N1 HPAI virus infection in wood ducks (Aix sponsa) was evaluated. Pre-exposure of wood ducks to different LPAI viruses did not prevent infection with H5N1 HPAI virus, but did increase survival associated with H5N1 HPAI virus infection. The magnitude of this effect on the outcome of the H5N1 HPAI virus infection varied between different LPAI viruses, and was associated both with efficiency of LPAI viral replication in wood ducks and the development of a detectable humoral immune response. These observations suggest that in naturally occurring outbreaks of H5N1 HPAI, birds with pre-existing immunity to homologous hemagglutinin or neuraminidase subtypes of AI virus may either survive H5N1 HPAI virus infection or live longer than naïve birds and, consequently, could pose a greater risk for contributing to viral transmission and dissemination. The mechanisms responsible for this protection and/or the duration of this immunity remain unknown. The results of this study are important for surveillance efforts and help clarify epidemiological data from outbreaks of H5N1 HPAI virus in wild bird populations. PMID:21253608

  11. 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...

  12. Airborne Transmission of Highly Pathogenic H7N1 Influenza Virus in Ferrets

    PubMed Central

    Finch, Courtney; Shao, Hongxia; Angel, Matthew; Chen, Hongjun; Capua, Ilaria; Cattoli, Giovanni; Monne, Isabella

    2014-01-01

    ABSTRACT Avian H7 influenza viruses are recognized as potential pandemic viruses, as personnel often become infected during poultry outbreaks. H7 infections in humans typically cause mild conjunctivitis; however, the H7N9 outbreak in the spring of 2013 has resulted in severe respiratory disease. To date, no H7 viruses have acquired the ability for sustained transmission among humans. Airborne transmission is considered a requirement for the emergence of pandemic influenza, and advanced knowledge of the molecular changes or signature required for transmission would allow early identification of pandemic vaccine seed stocks, screening and stockpiling of antiviral compounds, and eradication efforts focused on flocks harboring threatening viruses. Thus, we sought to determine if a highly pathogenic influenza A H7N1 (A/H7N1) virus with no history of human infection could become capable of airborne transmission among ferrets. We show that after 10 serial passages, A/H7N1 developed the ability to be transmitted to cohoused and airborne contact ferrets. Four amino acid mutations (PB2 T81I, NP V284M, and M1 R95K and Q211K) in the internal genes and a minimal amino acid mutation (K/R313R) in the stalk region of the hemagglutinin protein were associated with airborne transmission. Furthermore, transmission was not associated with loss of virulence. These findings highlight the importance of the internal genes in host adaptation and suggest that natural isolates carrying these mutations be further evaluated. Our results demonstrate that a highly pathogenic avian H7 virus can become capable of airborne transmission in a mammalian host, and they support ongoing surveillance and pandemic H7 vaccine development. IMPORTANCE The major findings of this report are that a highly pathogenic strain of H7N1 avian influenza virus can be adapted to become capable of airborne transmission in mammals without mutations altering receptor specificity. Changes in receptor specificity have been

  13. Egg-independent vaccine strategies for highly pathogenic H5N1 influenza viruses.

    PubMed

    Pandey, Aseem; Singh, Neetu; Sambhara, Suryaprakash; Mittal, Suresh K

    2010-02-01

    The emergence of a highly pathogenic H5N1 influenza virus in Hong Kong in 1997 and the subsequent appearance of other H5N1 strains and their spread to several countries in southeast Asia, Africa, the Middle East and Europe has evoked fear of a global influenza pandemic. Vaccines offer the best hope to combat the threat of an influenza pandemic. However, the global demand for a pandemic vaccine cannot be fulfilled by the current egg-based vaccine manufacturing strategies, thus creating a need to explore alternative technologies for vaccine production and delivery. Several egg-independent vaccine approaches such as cell culture-derived whole virus or subvirion vaccines, recombinant protein-based vaccines, virus-like particle (VLP) vaccines, DNA vaccines and viral vector-based vaccines are currently being investigated and appear promising both in preclinical and clinical studies. The present review will highlight the various egg-independent alternative vaccine approaches for pandemic influenza. PMID:19875936

  14. Survey for Highly Pathogenic Avian Influenza from Poultry in Two Northeastern States, Nigeria

    PubMed Central

    Musa, Ibrahim Waziri; Abdu, Paul Ayuba; Sackey, Anthony Kojo Bedu; Oladele, Sunday Blessing

    2013-01-01

    Highly pathogenic avian influenza (HPAI) is a major global zoonosis. It has a complex ecological distribution with almost unpredictable epidemiological features thus placing it topmost in the World Organization for Animal Health list A poultry diseases. Structured questionnaire survey of poultry farmer's knowledge, attitudes, and practices (KAP) in two Nigerian states revealed the presence of risk farming practices that may enable avian influenza high chance of introduction/reintroduction. There existed significant statistical association between farmer's educational levels and AI awareness and zoonotic awareness (P < 0.005). Poultry rearing of multiage and species (81%), multiple sources of stock (62%), inadequate dead-bird disposal (71%), and access to live bird markets (LBMs) (62%) constituted major biosecurity threats in these poultry farming communities. Haemagglutination inhibition (HI) test detected antibodies against H5 avian influenza (AI) in 8 of the 400 sera samples; rapid antigen detection test kit (RADTK) was negative for all the 400 cloaca and trachea swabs. These results and other poultry diseases similar to AI observed in this study could invariably affect avian influenza early detection, reporting, and control. We recommend strong policy initiatives towards poultry farmers' attitudinal change and increasing efforts on awareness of the implications of future HPAI outbreaks in Nigeria. PMID:23936731

  15. Vaccination and acute phase mediator production in chickens challenged with low pathogenic avian influenza virus; novel markers for vaccine efficacy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Methods to determine vaccine efficacy of low pathogenic avian influenza (LPAI) isolates are limited in poultry because experimental infections with LPAI virus in specific pathogen free chickens rarely causes clinical disease. The most commonly used method to compare LPAI vaccine efficacy is to quant...

  16. Characaterization of H5N1 highly pathogenic avian influenza viruses isolated from poultry in Pakistan 2006-2008

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nine avian influenza viruses (AIV), H5N1 subtype, were isolated from dead poultry in the Karachi region of Pakistan from 2006-2008. The intravenous pathogenicity indices and HA protein cleavage sites of all nine viruses were consistent with highly pathogenic AIV. Based on phylogenetic analysis of ...

  17. Innate immune responses to infection with H5N1 highly pathogenic avian influenza virus in different duck species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ducks have been implicated in the dissemination and evolution of H5N1 highly pathogenic avian influenza (HPAI) viruses. Differences in pathogenicity and response to vaccination have been observed between different duck species. The innate immune system is responsible for controlling viruses during t...

  18. Acid Stability of the Hemagglutinin Protein Regulates H5N1 Influenza Virus Pathogenicity

    SciTech Connect

    DuBois, Rebecca M.; Zaraket, Hassan; Reddivari, Muralidhar; Heath, Richard J.; White, Stephen W.; Russell, Charles J.

    2012-12-10

    Highly pathogenic avian influenza viruses of the H5N1 subtype continue to threaten agriculture and human health. Here, we use biochemistry and x-ray crystallography to reveal how amino-acid variations in the hemagglutinin (HA) protein contribute to the pathogenicity of H5N1 influenza virus in chickens. HA proteins from highly pathogenic (HP) A/chicken/Hong Kong/YU562/2001 and moderately pathogenic (MP) A/goose/Hong Kong/437-10/1999 isolates of H5N1 were found to be expressed and cleaved in similar amounts, and both proteins had similar receptor-binding properties. However, amino-acid variations at positions 104 and 115 in the vestigial esterase sub-domain of the HA1 receptor-binding domain (RBD) were found to modulate the pH of HA activation such that the HP and MP HA proteins are activated for membrane fusion at pH 5.7 and 5.3, respectively. In general, an increase in H5N1 pathogenicity in chickens was found to correlate with an increase in the pH of HA activation for mutant and chimeric HA proteins in the observed range of pH 5.2 to 6.0. We determined a crystal structure of the MP HA protein at 2.50 {angstrom} resolution and two structures of HP HA at 2.95 and 3.10 {angstrom} resolution. Residues 104 and 115 that modulate the acid stability of the HA protein are situated at the N- and C-termini of the 110-helix in the vestigial esterase sub-domain, which interacts with the B loop of the HA2 stalk domain. Interactions between the 110-helix and the stalk domain appear to be important in regulating HA protein acid stability, which in turn modulates influenza virus replication and pathogenesis. Overall, an optimal activation pH of the HA protein is found to be necessary for high pathogenicity by H5N1 influenza virus in avian species.

  19. Recovery Based Nanowire Field-Effect Transistor Detection of Pathogenic Avian Influenza DNA

    NASA Astrophysics Data System (ADS)

    Lin, Chih-Heng; Chu, Chia-Jung; Teng, Kang-Ning; Su, Yi-Jr; Chen, Chii-Dong; Tsai, Li-Chu; Yang, Yuh-Shyong

    2012-02-01

    Fast and accurate diagnosis is critical in infectious disease surveillance and management. We proposed a DNA recovery system that can easily be adapted to DNA chip or DNA biosensor for fast identification and confirmation of target DNA. This method was based on the re-hybridization of DNA target with a recovery DNA to free the DNA probe. Functionalized silicon nanowire field-effect transistor (SiNW FET) was demonstrated to monitor such specific DNA-DNA interaction using high pathogenic strain virus hemagglutinin 1 (H1) DNA of avian influenza (AI) as target. Specific electric changes were observed in real-time for AI virus DNA sensing and device recovery when nanowire surface of SiNW FET was modified with complementary captured DNA probe. The recovery based SiNW FET biosensor can be further developed for fast identification and further confirmation of a variety of influenza virus strains and other infectious diseases.

  20. The live bird market system and low-pathogenic avian influenza prevention in southern California.

    PubMed

    Yee, Karen S; Carpenter, Tim E; Mize, Sarah; Cardona, Carol J

    2008-06-01

    Although live bird markets (LBMs) have been associated with outbreaks of avian influenza (AI), there are some LBM systems where AI outbreaks are extremely rare events. The California LBMs have not had any detected avian influenza viruses (AIVs) since December 2005. Responses to a detailed questionnaire on the practices and characteristics of the participants in the California low-pathogenic (LP) AI control program have been described to characterize possible reasons for the lack of AI outbreaks in LBMs. Compliance with an LPAI control program that contains active surveillance, prevention, and rapid response measures by those involved in the LBM system, rendering services to dispose of carcasses, no wholesalers, and few third-party bird deliveries was associated with the lack of LPAIV circulating in the Southern California LBM system. PMID:18646469

  1. Assessment of reduced vaccine dose on efficacy of an inactivated avian influenza vaccine against an H5N1 high pathogenicity avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza (AI) vaccines have emerged to be a viable emergency tool for use in a comprehensive strategy for dealing with high pathogenicity (HP) AI in developed countries. However, the available doses of inactivated AI vaccine are limited to national vaccine banks and inventory stocks of some ...

  2. Lemna (duckweed) expressed hemagglutinin from avian influenza H5N1 protects chickens against H5N1 high pathogenicity avian influenza virus challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the last two decades, transgenic plants have been explored as safe and cost effective alternative expression platforms for producing recombinant proteins. In this study, a synthetic hemagglutinin (HA) gene from the high pathogenicity avian influenza (HPAI) virus A/chicken/Indonesia/7/2003 (H5N1)...

  3. EFFICACY OF A FOWLPOX-VECTORED AVIAN INFLUENZA H5 VACCINE AGAINST ASIAN H5N1 HIGHLY PATHOGENIC AVIAN INFLUENZA VIRUS CHALLENGE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A recombinant fowlpox-avian influenza (AI) H5 vaccine (rFP-AIV-H5) expressing the hemagglutinin of the A/turkey/Ireland/1378/83 H5N8 AI isolate has been used in Central America since 1998 to control H5N2 low pathogenicity (LP) AI. Previously, this vaccine was shown to induce full protection against...

  4. Potency, efficacy, and antigenic mapping of H7 avian influenza virus vaccines against the 2012 H7N3 highly pathogenic avian influenza virus from Mexico

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the spring of 2012 an outbreak of H7N3 highly pathogenic (HP) avian influenza virus (AIV) occurred in poultry in Mexico. Vaccination was implemented as a control measure along with increased biosecurity and surveillance. At that time there was no commercially available H7 AIV vaccine in North Ame...

  5. Protection against H7N3 high pathogenicity avian influenza in chickens immunized with a recombinant fowlpox and an inactivated avian influenza vaccines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Beginning on June 2012, an H7N3 highly pathogenic avian influenza (HPAI) epizootic was reported in the State of Jalisco (Mexico), with some 22.4 million chickens that died, were slaughtered on affected farms or were preemptively culled on neighboring farms. In the current study, layer chickens were ...

  6. Efficacy of inactivated influenza vaccines for protection of poultry against the H7N9 low pathogenic avian influenza virus isolated in China during 2013

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The recent outbreak in China of avian influenza (AI) H7N9 in birds and humans underscores the interspecies movement of these viruses. Interestingly, the genetic composition of these H7N9 viruses appears to be solely of avian origin and of low pathogenicity in birds. Although few isolations of these ...

  7. 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...

  8. Protection of poultry against the 2012 Mexican H7N3 highly pathogenic avian influenza virus with inactivated H7 avian influenza vaccines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In June of 2012, an outbreak of highly pathogenic avian influenza (HPAI) H7N3 was reported poultry in Jalisco, Mexico. Since that time the virus has spread to the surrounding States of Guanajuato and Aguascalientes and new outbreaks continue to be reported. To date more than 25 million birds have di...

  9. Vaccine protection of turkeys against H5N1 highly pathogenic avian influenza virus with a recombinant HVT expressing the hemagglutinin gene of avian influenza

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Outbreaks of H5 highly pathogenic avian influenza (HPAI) in commercial poultry are a constant threat to animal health and food supplies. While vaccination can enhance protection and reduce the spread of disease, there is considerable evidence that the level of immunity required for protection varies...

  10. Novel Highly Pathogenic Avian H5 Influenza A Viruses in Live Poultry Markets, Wuxi City, China, 2013−2014

    PubMed Central

    Ma, Mai-Juan; Chen, Shan-Hui; Wang, Guo-Lin; Zhao, Teng; Qian, Yan-Hua; Wu, Meng-Na; Liu, Ying; Gray, Gregory C.; Lu, Bing; Cao, Wu-Chun

    2016-01-01

    During 12 recent months of periodic influenza virus surveillance at 9 live poultry markets in Wuxi City China, we identified multiple highly pathogenic H5N6, H5N8, H5N2, and H5N1 avian influenza viruses. The variety of potentially pandemic viruses in this low-risk area is disconcerting and portends an increased pandemic threat. PMID:27186580

  11. Highly pathogenic influenza H5N1 virus of clade 2.3.2.1c in Western Siberia.

    PubMed

    Marchenko, V Y; Susloparov, I M; Kolosova, N P; Goncharova, N I; Shipovalov, A V; Ilyicheva, T N; Durymanov, A G; Chernyshova, O A; Kozlovskiy, L I; Chernyshova, T V; Pryadkina, E N; Karimova, T V; Mikheev, V N; Ryzhikov, A B

    2016-06-01

    In the spring of 2015, avian influenza virus surveillance in Western Siberia resulted in isolation of several influenza H5N1 virus strains. The strains were isolated from several wild bird species. Investigation of biological features of those strains demonstrated their high pathogenicity for mammals. Phylogenetic analysis of the HA gene showed that the strains belong to clade 2.3.2.1c. PMID:26935914

  12. 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

  13. Isolation and characterization of highly pathogenic avian influenza virus subtype H5N1 from donkeys

    PubMed Central

    2010-01-01

    Background The highly pathogenic H5N1 is a major avian pathogen that crosses species barriers and seriously affects humans as well as some mammals. It mutates in an intensified manner and is considered a potential candidate for the possible next pandemic with all the catastrophic consequences. Methods Nasal swabs were collected from donkeys suffered from respiratory distress. The virus was isolated from the pooled nasal swabs in specific pathogen free embryonated chicken eggs (SPF-ECE). Reverse transcriptase polymerase chain reaction (RT-PCR) and sequencing of both haemagglutingin and neuraminidase were performed. H5 seroconversion was screened using haemagglutination inhibition (HI) assay on 105 donkey serum samples. Results We demonstrated that H5N1 jumped from poultry to another mammalian host; donkeys. Phylogenetic analysis showed that the virus clustered within the lineage of H5N1 from Egypt, closely related to 2009 isolates. It harboured few genetic changes compared to the closely related viruses from avian and humans. The neuraminidase lacks oseltamivir resistant mutations. Interestingly, HI screening for antibodies to H5 haemagglutinins in donkeys revealed high exposure rate. Conclusions These findings extend the host range of the H5N1 influenza virus, possess implications for influenza virus epidemiology and highlight the need for the systematic surveillance of H5N1 in animals in the vicinity of backyard poultry units especially in endemic areas. PMID:20398268

  14. Using Extreme Value Theory Approaches to Forecast the Probability of Outbreak of Highly Pathogenic Influenza in Zhejiang, China

    PubMed Central

    Chen, Jiangpeng; Lei, Xun; Zhang, Li; Peng, Bin

    2015-01-01

    Background Influenza is a contagious disease with high transmissibility to spread around the world with considerable morbidity and mortality and presents an enormous burden on worldwide public health. Few mathematical models can be used because influenza incidence data are generally not normally distributed. We developed a mathematical model using Extreme Value Theory (EVT) to forecast the probability of outbreak of highly pathogenic influenza. Methods The incidence data of highly pathogenic influenza in Zhejiang province from April 2009 to November 2013 were retrieved from the website of Health and Family Planning Commission of Zhejiang Province. MATLAB “VIEM” toolbox was used to analyze data and modelling. In the present work, we used the Peak Over Threshold (POT) model, assuming the frequency as a Poisson process and the intensity to be Pareto distributed, to characterize the temporal variability of the long-term extreme incidence of highly pathogenic influenza in Zhejiang, China. Results The skewness and kurtosis of the incidence of highly pathogenic influenza in Zhejiang between April 2009 and November 2013 were 4.49 and 21.12, which indicated a “fat tail” distribution. A QQ plot and a mean excess plot were used to further validate the features of the distribution. After determining the threshold, we modeled the extremes and estimated the shape parameter and scale parameter by the maximum likelihood method. The results showed that months in which the incidence of highly pathogenic influenza is about 4462/2286/1311/487 are predicted to occur once every five/three/two/one year, respectively. Conclusions Despite the simplicity, the present study successfully offers the sound modeling strategy and a methodological avenue to implement forecasting of an epidemic in the midst of its course. PMID:25710503

  15. 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. PMID:26814367

  16. Transcriptional analysis of the innate immune response of ducks to different species-of-origin low pathogenic H7 avian influenza viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Ducks represent an important reservoir for avian influenza (AI) viruses and are partly responsible for the worldwide dissemination of AI. Due to the ability of some low pathogenicity avian influenza viruses (LPAIV) of the hemagglutinin H7 subtype to mutate into a highly pathogenic form o...

  17. Ferrets develop fatal influenza after inhaling small particle aerosols of highly pathogenic avian influenza virus A/Vietnam/1203/2004 (H5N1)

    PubMed Central

    2010-01-01

    Background 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 animal model for humans in influenza pathogenicity and transmissibility studies. In this manuscript, a nose-only bioaerosol inhalation exposure system that was recently developed and validated was used in an inhalation exposure study of aerosolized A/Vietnam/1203/2004 (H5N1) virus in ferrets. The clinical spectrum of influenza resulting from exposure to A/Vietnam/1203/2004 (H5N1) through intranasal verses inhalation routes was analyzed. Results Ferrets were successfully infected through intranasal instillation or through inhalation of small particle aerosols with four different doses of Influenza virus A/Vietnam/1203/2004 (H5N1). The animals developed severe influenza encephalomyelitis following intranasal or inhalation exposure to 101, 102, 103, or 104 infectious virus particles per ferret. Conclusions Aerosolized Influenza virus A/Vietnam/1203/2004 (H5N1) is highly infectious and lethal in ferrets. Clinical signs appeared earlier in animals infected through inhalation of aerosolized virus compared to those infected through intranasal instillation. PMID:20843329

  18. Characterization of a novel highly pathogenic H5N2 avian influenza virus isolated from a duck in eastern China.

    PubMed

    Wu, Haibo; Peng, Xiaorong; Xu, Lihua; Jin, Changzhong; Cheng, Linfang; Lu, Xiangyun; Xie, Tiansheng; Yao, Hangping; Wu, Nanping

    2014-12-01

    During surveillance for avian influenza viruses (AIVs) in live-poultry markets (LPMs) in eastern China in 2013, one H5N2 AIV was isolated from a duck. Phylogenetic analysis showed that the hemagglutinin of this strain belongs to clade 2.3.4 and received its genes from H5, H3 and H6 AIVs of poultry in China. The virulence of this strain was examined in chickens and mice, and it was found to be highly pathogenic in chickens but demonstrated moderate pathogenicity in mice. These results suggest that active surveillance of AIVs in LPMs should be used in an early warning system for avian influenza outbreaks. PMID:25091744

  19. Differences in pathogenicity and response to vaccination between Pekin and Muscovy ducks infected with H5N1 highly pathogenic influenza viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ducks have been implicated in the dissemination and evolution of H5N1 highly pathogenic avian influenza (HPAI) viruses. Vaccination of domestic ducks against H5N1 HPAI is being conducted as a method of control but with mixed results. One of the observations from the field is that Muscovy ducks (Cair...

  20. Comparison of molecular classification and experimental pathogenicity for classification of low and high pathogenicity H5 and H7 avian influenza viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Highly pathogenic avian influenza (HPAI) viruses, which have been restricted to H5 and H7 subtypes, have caused continuous outbreaks in the poultry industry with devastating economic losses and is a severe threat to public health. Genetic features and severity of the disease in poultry determine wh...

  1. Differences in pathogenicity of A/Duck/Vietnam/201/05 H5N1 highly pathogenic avian influenza virus reassortants in ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In order to understand which viral genes contribute to the high virulence of A/Dk/Vietnam/201/05 H5N1 highly pathogenic avian influenza (HPAI) virus in ducks, we used reverse genetics to generate single-gene reassortant viruses with genes from A/Ck/Indonesia/7/03, a virus that produces mild disease ...

  2. A High Diversity of Eurasian Lineage Low Pathogenicity Avian Influenza A Viruses Circulate among Wild Birds Sampled in Egypt

    PubMed Central

    Gerloff, Nancy A.; Jones, Joyce; Simpson, Natosha; Balish, Amanda; ElBadry, Maha Adel; Baghat, Verina; Rusev, Ivan; de Mattos, Cecilia C.; de Mattos, Carlos A.; Zonkle, Luay Elsayed Ahmed; Kis, Zoltan; Davis, C. Todd; Yingst, Sam; Cornelius, Claire; Soliman, Atef; Mohareb, Emad; Klimov, Alexander; Donis, Ruben O.

    2013-01-01

    Surveillance for influenza A viruses in wild birds has increased substantially as part of efforts to control the global movement of highly pathogenic avian influenza A (H5N1) virus. Studies conducted in Egypt from 2003 to 2007 to monitor birds for H5N1 identified multiple subtypes of low pathogenicity avian influenza A viruses isolated primarily from migratory waterfowl collected in the Nile Delta. Phylogenetic analysis of 28 viral genomes was performed to estimate their nearest ancestors and identify possible reassortants. Migratory flyway patterns were included in the analysis to assess gene flow between overlapping flyways. Overall, the viruses were most closely related to Eurasian, African and/or Central Asian lineage low pathogenicity viruses and belonged to 15 different subtypes. A subset of the internal genes seemed to originate from specific flyways (Black Sea-Mediterranean, East African-West Asian). The remaining genes were derived from a mixture of viruses broadly distributed across as many as 4 different flyways suggesting the importance of the Nile Delta for virus dispersal. Molecular clock date estimates suggested that the time to the nearest common ancestor of all viruses analyzed ranged from 5 to 10 years, indicating frequent genetic exchange with viruses sampled elsewhere. The intersection of multiple migratory bird flyways and the resulting diversity of influenza virus gene lineages in the Nile Delta create conditions favoring reassortment, as evident from the gene constellations identified by this study. In conclusion, we present for the first time a comprehensive phylogenetic analysis of full genome sequences from low pathogenic avian influenza viruses circulating in Egypt, underscoring the significance of the region for viral reassortment and the potential emergence of novel avian influenza A viruses, as well as representing a highly diverse influenza A virus gene pool that merits continued monitoring. PMID:23874653

  3. [Haemophilus influenzae b: a review on the determinants of pathogenicity and immune response to the infection].

    PubMed

    Gómez de León, P; Cabrera-Contreras, R; Cravioto, A

    1991-01-01

    Haemophilus influenzae is still one of the main causes of diverse invasive diseases in children in México. Epidemiologic data indicate that these processes affect primarily the central nervous system and the respiratory tract. Several factors are involved in the expression of infectious disease by this organism, among them the pathogenic determinants of the parasite and those related with resistance in the host. Occurrence of disease is usually the result of the interaction between these determinants. Knowledge of these pathogenic determinants of the parasite and of factors involved in the immune response of the host have allowed an understanding of the infectious process and have directed research in a least three areas: 1) identification of bacterial membrane fractions related with diagnosis of the disease, 2) screening for immunogenic components in the bacterias as vaccine candidates to be used in the prevention of the disease and, 3) the planning of appropriate alternatives for specific antimicrobial therapy. PMID:1948428

  4. Susceptibility of rock doves to low-pathogenic avian influenza A viruses.

    PubMed

    Shriner, Susan A; Root, J Jeffrey; Mooers, Nicole L; Ellis, Jeremy W; Stopak, Scott R; Sullivan, Heather J; VanDalen, Kaci K; Franklin, Alan B

    2016-03-01

    Following a 2008 outbreak of North American low-pathogenic H5N8 influenza A virus at an upland gamebird farm, we sero-sampled rock doves (pigeons, Columba livia) at the outbreak site and conducted experimental inoculations of wild-caught pigeons using the H5N8 virus and another low-pathogenic virus (H4N6). While 13% of pigeons at the outbreak site were seropositive, none were positive for exposure to H5, and one was positive for N8. Challenged pigeons exhibited low susceptibility and limited viral RNA excretion for both viruses tested, but at least one individual had RNA loads indicative of the potential for viral transmission to other birds. PMID:26687583

  5. H5N1 influenza virulence, pathogenicity and transmissibility: what do we know?

    PubMed Central

    Neumann, Gabriele

    2015-01-01

    Highly pathogenic influenza viruses of the H5N1 subtype have infected more than 600 people since 1997, resulting in the deaths of approximately 60% of those infected. Multiple studies have established the viral hemagglutinin (HA) surface glycoprotein as the major determinant of H5N1 virulence. HA mediates host-specific virus binding to cells, and mutations that allow efficient binding to viral receptors on mammalian cells are critical (although not sufficient) for H5N1 transmissibility among mammals. The viral polymerase PB2 protein is also a critical virulence determinant, and adaptive mutations in this protein are crucial for efficient H5N1 virus replication in mammals. Additionally, viral proteins (such as NS1 and PB1-F2) with roles in innate immune responses also affect the virulence of highly pathogenic H5N1 viruses. PMID:26617665

  6. Highly Pathogenic Avian Influenza H5N8 in Germany: Outbreak Investigations.

    PubMed

    Conraths, F J; Sauter-Louis, C; Globig, A; Dietze, K; Pannwitz, G; Albrecht, K; Höreth-Böntgen, D; Beer, M; Staubach, C; Homeier-Bachmann, T

    2016-02-01

    Epidemiological outbreak investigations were conducted in highly pathogenic avian influenza virus of the subtype H5N8 (HPAIV H5N8)-affected poultry holdings and a zoo to identify potential routes of entry of the pathogen via water, feedstuffs, animals, people, bedding material, other fomites (equipment, vehicles etc.) and the presence of wild birds near affected holdings. Indirect introduction of HPAIV H5N8 via material contaminated by infected wild bird seems the most reasonable explanation for the observed outbreak series in three commercial holdings in Mecklenburg-Western Pomerania and Lower Saxony, while direct contact to infected wild birds may have led to outbreaks in a zoo in Rostock and in two small free-range holdings in Anklam, Mecklenburg-Western Pomerania. PMID:26519355

  7. 2.1 Natural History of Highly Pathogenic Avian Influenza H5N1

    PubMed Central

    Sonnberg, Stephanie; Webby, Richard J.; Webster, Robert G.

    2013-01-01

    The ecology of highly pathogenic avian influenza (HPAI) H5N1 has significantly changed from sporadic outbreaks in terrestrial poultry to persistent circulation in terrestrial and aquatic poultry and potentially in wild waterfowl. A novel genotype of HPAI H5N1 arose in 1996 in southern China and through ongoing mutation, reassortment, and natural selection, has diverged into distinct lineages and expanded into multiple reservoir hosts. The evolution of Goose/Guangdong-lineage highly pathogenic H5N1 viruses is ongoing: while stable interactions exist with some reservoir hosts, these viruses are continuing to evolve and adapt to others, and pose an un-calculable risk to sporadic hosts, including humans. PMID:23735535

  8. Extended Viral Shedding of a Low Pathogenic Avian Influenza Virus by Striped Skunks (Mephitis mephitis)

    PubMed Central

    Root, J. Jeffrey; Shriner, Susan A.; Bentler, Kevin T.; Gidlewski, Thomas; Mooers, Nicole L.; Ellis, Jeremy W.; Spraker, Terry R.; VanDalen, Kaci K.; Sullivan, Heather J.; Franklin, Alan B.

    2014-01-01

    Background Striped skunks (Mephitis mephitis) are susceptible to infection with some influenza A viruses. However, the viral shedding capability of this peri-domestic mammal and its potential role in influenza A virus ecology are largely undetermined. Methodology/Principal Findings Striped skunks were experimentally infected with a low pathogenic (LP) H4N6 avian influenza virus (AIV) and monitored for 20 days post infection (DPI). All of the skunks exposed to H4N6 AIV shed large quantities of viral RNA, as detected by real-time RT-PCR and confirmed for live virus with virus isolation, from nasal washes and oral swabs (maximum ≤106.02 PCR EID50 equivalent/mL and ≤105.19 PCR EID50 equivalent/mL, respectively). Some evidence of potential fecal shedding was also noted. Following necropsy on 20 DPI, viral RNA was detected in the nasal turbinates of one individual. All treatment animals yielded evidence of a serological response by 20 DPI. Conclusions/Significance These results indicate that striped skunks have the potential to shed large quantities of viral RNA through the oral and nasal routes following exposure to a LP AIV. Considering the peri-domestic nature of these animals, along with the duration of shedding observed in this species, their presence on poultry and waterfowl operations could influence influenza A virus epidemiology. For example, this species could introduce a virus to a naive poultry flock or act as a trafficking mechanism of AIV to and from an infected poultry flock to naive flocks or wild bird populations. PMID:24489638

  9. Modelling the wind-borne spread of highly pathogenic avian influenza virus between farms.

    PubMed

    Ssematimba, Amos; Hagenaars, Thomas J; de Jong, Mart C M

    2012-01-01

    A quantitative understanding of the spread of contaminated farm dust between locations is a prerequisite for obtaining much-needed insight into one of the possible mechanisms of disease spread between farms. Here, we develop a model to calculate the quantity of contaminated farm-dust particles deposited at various locations downwind of a source farm and apply the model to assess the possible contribution of the wind-borne route to the transmission of Highly Pathogenic Avian Influenza virus (HPAI) during the 2003 epidemic in the Netherlands. The model is obtained from a Gaussian Plume Model by incorporating the dust deposition process, pathogen decay, and a model for the infection process on exposed farms. Using poultry- and avian influenza-specific parameter values we calculate the distance-dependent probability of between-farm transmission by this route. A comparison between the transmission risk pattern predicted by the model and the pattern observed during the 2003 epidemic reveals that the wind-borne route alone is insufficient to explain the observations although it could contribute substantially to the spread over short distance ranges, for example, explaining 24% of the transmission over distances up to 25 km. PMID:22348042

  10. Models of highly pathogenic avian influenza epidemics in commercial poultry flocks in Nigeria and Ghana

    PubMed Central

    Pelletier, Sky T. K.; Rorres, Chris; Macko, Peter C.; Peters, Sarah

    2013-01-01

    State-scale and premises-scale gravity models for the spread of highly pathogenic avian influenza (H5N1) in Nigeria and Ghana were used to provide a basis for risk maps for future epidemics and to compare and rank plausible culling and vaccination strategies for control. Maximum likelihood methods were used to fit the models to the 2006–2007 outbreaks. The sensitivity and specificity of the state-scale model-generated probabilities that any given state would be involved in an epidemic were each 57 %. The premises-based model indicated that reactive, countrywide vaccination strategies, in which the order in which flocks are vaccinated was strictly determined by known risk factors for infection, were more effective in reducing the final size of the epidemic and the epidemic impact than vaccinating flocks at random or ring vaccination. The model suggests that an introduction of highly pathogenic avian influenza (H5N1) into Ghana had a high chance (84 %) of causing a major outbreak. That this did not happen was most probably a result of the very swift Ghanaian response to news of the first introductions. PMID:22476732

  11. Alterations in Hemagglutinin Receptor-Binding Specificity Accompany the Emergence of Highly Pathogenic Avian Influenza Viruses

    PubMed Central

    Mochalova, Larisa; Harder, Timm; Tuzikov, Alexander; Bovin, Nicolai; Wolff, Thorsten; Matrosovich, Mikhail; Schweiger, Brunhilde

    2015-01-01

    ABSTRACT Highly pathogenic avian influenza viruses (HPAIVs) of hemagglutinin H5 and H7 subtypes emerge after introduction of low-pathogenic avian influenza viruses (LPAIVs) from wild birds into poultry flocks, followed by subsequent circulation and evolution. The acquisition of multiple basic amino acids at the endoproteolytical cleavage site of the hemagglutinin (HA) is a molecular indicator for high pathogenicity, at least for infections of gallinaceous poultry. Apart from the well-studied significance of the multibasic HA cleavage site, there is only limited knowledge on other alterations in the HA and neuraminidase (NA) molecules associated with changes in tropism during the emergence of HPAIVs from LPAIVs. We hypothesized that changes in tropism may require alterations of the sialyloligosaccharide specificities of HA and NA. To test this hypothesis, we compared a number of LPAIVs and HPAIVs for their HA-mediated binding and NA-mediated desialylation of a set of synthetic receptor analogs, namely, α2-3-sialylated oligosaccharides. NA substrate specificity correlated with structural groups of NAs and did not correlate with pathogenic potential of the virus. In contrast, all HPAIVs differed from LPAIVs by a higher HA receptor-binding affinity toward the trisaccharides Neu5Acα2-3Galβ1-4GlcNAcβ (3′SLN) and Neu5Acα2-3Galβ1-3GlcNAcβ (SiaLec) and by the ability to discriminate between the nonfucosylated and fucosylated sialyloligosaccharides 3′SLN and Neu5Acα2-3Galβ1-4(Fucα1-3)GlcNAcβ (SiaLex), respectively. These results suggest that alteration of the receptor-binding specificity accompanies emergence of the HPAIVs from their low-pathogenic precursors. IMPORTANCE Here, we have found for the first time correlations of receptor-binding properties of the HA with a highly pathogenic phenotype of poultry viruses. Our study suggests that enhanced receptor-binding affinity of HPAIVs for a typical “poultry-like” receptor, 3′SLN, is provided by

  12. Emergence of H5N1 high pathogenicity avian influenza strains in Indonesia that are resistant to vaccines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vaccines have been used to protect poultry in Asia against H5N1 high pathogenicity avian influenza (HPAI) since 2002. Reports of vaccine “failures” began to emerge in 2006 in Indonesia, with identification of clinical disease consistent with HPAI or isolation of H5N1 HPAIV in vaccinated flocks or in...

  13. What are the possible transmission methods for H5N1 high pathogenicity avian influenza viruses to people

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The H5N1 high pathogenicity avian influenza (HPAI) virus has caused an unprecedented epizootic affecting poultry in Asia, Africa and parts of Europe, but has crossed multiple species barriers to infect captive and wild birds, carnivorous mammals and humans. Human infections (391 infections with 247...

  14. 9 CFR 146.14 - Diagnostic surveillance program for H5/H7 low pathogenic avian influenza.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Diagnostic surveillance program for H5/H7 low pathogenic avian influenza. 146.14 Section 146.14 Animals and Animal Products ANIMAL AND PLANT... antigen detection test. Memoranda of understanding or other means must be used to establish testing...

  15. 9 CFR 146.14 - Diagnostic surveillance program for H5/H7 low pathogenic avian influenza.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Diagnostic surveillance program for H5/H7 low pathogenic avian influenza. 146.14 Section 146.14 Animals and Animal Products ANIMAL AND PLANT... antigen detection test. Memoranda of understanding or other means must be used to establish testing...

  16. 9 CFR 146.14 - Diagnostic surveillance program for H5/H7 low pathogenic avian influenza.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Diagnostic surveillance program for H5/H7 low pathogenic avian influenza. 146.14 Section 146.14 Animals and Animal Products ANIMAL AND PLANT... antigen detection test. Memoranda of understanding or other means must be used to establish testing...

  17. 9 CFR 146.14 - Diagnostic surveillance program for H5/H7 low pathogenic avian influenza.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Diagnostic surveillance program for H5/H7 low pathogenic avian influenza. 146.14 Section 146.14 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE LIVESTOCK IMPROVEMENT NATIONAL POULTRY IMPROVEMENT PLAN FOR COMMERCIAL POULTRY...

  18. Co-infection of mallards with low virulence Newcastle disease virus and low pathogenic avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Waterfowl are considered the natural reservoirs of low pathogenic avian influenza viruses (LPAIV) and low virulence Newcastle disease viruses (loNDV). The objective of this study was to investigate the effect of co-infections with loNDV and LPAIV on the infectivity and excretion of these viruses in ...

  19. Mechanisms of transmission and spread of H5N1 high pathogenicity avian influenza virus in birds and mammals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Eurasian-African H5N1 high pathogenicity avian influenza (HPAI) virus has crossed multiple species barriers to infect poultry, captive and wild birds, carnivorous mammals and humans. The specific transmission mechanisms are unclear in most cases, but experimental studies and field data sug...

  20. The pathobiology of highly pathogenic H5N2 avian influenza virus in Ruddy ducks and Lesser Scaup

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The susceptibility and pathogenesis of avian influenza virus (AIV) has not been characterized in numerous duck species, especially diving ducks, some of which migrate across the continental U.S. The pathobiology of highly pathogenic (HP) H5N2 AIV was characterized in two diving duck species, Ruddy ...

  1. 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...

  2. THERMAL INACTIVATION OF H5N1 HIGH PATHOGENICITY AVIAN INFLUENZA VIRUS IN NATURALLY INFECTED CHICKEN MEAT

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Thermal inactivation of the H5N1 high pathogenicity avian influenza (HPAI) virus strain A/chicken/Korea/ES/2003 (Korea/03) was quantitatively measured in thigh and breast meat harvested from infected chickens. The average Korea/03 titers in uncooked meat samples were 8.0 log 10 EID50/g (thigh) and 7...

  3. 9 CFR 146.14 - Diagnostic surveillance program for H5/H7 low pathogenic avian influenza.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Diagnostic surveillance program for H5/H7 low pathogenic avian influenza. 146.14 Section 146.14 Animals and Animal Products ANIMAL AND PLANT... antigen detection test. Memoranda of understanding or other means must be used to establish testing...

  4. Characterization of 10 adjuvants for inactivated avian influenza virus (AIV) vaccines against challenge with highly pathogenic AIV in chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Inactivated vaccines comprise 95% of all vaccine used for avian influenza virus (AIV) by dose. Optimizing the adjuvant is one way to improve vaccine efficacy. Inactivated vaccines were produced with beta-propiolactone inactivated A/chicken/BC/314514-1/2004 H7N3 low pathogenicity AIV and standardiz...

  5. Efficacy of commercial vaccines in chickens and ducks against H5N1 highly pathogenic avian influenza viruses from Vietnam

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Highly pathogenic (HP) H5N1 avian influenza (AI) viruses continue to circulate in Asia and have spread to other regions of the world. Though attempts at eradication of the viruses during various outbreaks have been successful for short periods of time, new strains of H5N1 viruses continue to emerge...

  6. Detection of H5N1 high pathogenicity avian influenza virus in meat and tracheal samples from experimentally infected chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Asian H5N1 highly pathogenic avian influenza (HPAI) virus causes a systemic disease with high mortality of poultry and is potentially zoonotic. In both chickens and ducks, the virus has been demonstrated to replicate in both cardiac and skeletal muscle cells. Experimentally, H5N1 HPAI virus ha...

  7. 75 FR 17368 - Notice of Availability of an Evaluation of the Highly Pathogenic Avian Influenza Status of Czech...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-06

    ... additional risk factors that would indicate that domestic poultry in the Czech Republic and Sweden continue... introduction of diseases and pests into the U.S. livestock and poultry populations. Highly pathogenic avian influenza (HPAI) is a zoonotic disease of poultry. The H5N1 subtype of HPAI is an extremely infectious...

  8. 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.; Torchetti, Mia Kim; 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.

  9. Surveillance for Highly Pathogenic Avian Influenza Virus in Wild Birds during Outbreaks in Domestic Poultry, Minnesota, 2015.

    PubMed

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

    2016-07-01

    In 2015, a major outbreak of highly pathogenic avian influenza virus (HPAIV) infection devastated poultry facilities in Minnesota, USA. To understand the potential 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 fecal samples. PMID:27064759

  10. Pathobiological characterization of low-pathogenicity H5 avian influenza viruses of diverse origins in chickens, ducks and turkeys

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We undertook one of the most comprehensive studies on the replication and intraspecies transmission characteristics of 20 low pathogenicity avian influenza viruses of different origins, which included 8 isolates from wild aquatic birds. We studied virus replication in infected and contact control bi...

  11. 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; 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.

  12. 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

  13. Outbreaks of highly pathogenic Eurasian H5N8 avian influenza in two commercial poultry flocks in California

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In January 2015, a highly pathogenic Eurasian lineage H5N8 avian influenza (AI) virus was detected in a commercial meat turkey flock in Stanislaus County, California. Approximately 3 weeks later, a similar case was diagnosed in commercial chickens from a different company located in Kings County, C...

  14. NS1 gene truncations partially attenuate H5N1 highly pathogenic avian influenza viruses in chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The polybasic amino acid sequence in the hemagglutinin (HA) protein of H5 and H7 avian influenza (AI) viruses determines the high pathogenicity (HP) phenotype in chickens. The NS1 protein plays an important role in blocking the induction of antiviral defenses and other regulatory functions and thus...

  15. Susceptibility of selected wild avian species to experimental infection with H5N1 high pathogenicity avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since 2002, H5N1 highly pathogenic avian influenza (HPAI) viruses have caused mortality in wide diversity of wild avian species but, to date, the role that different species play in the transmission and maintenance of H5N1 HPAI viruses is poorly understood. To begin to address these uncertainties a...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study we biologically characterized H6N2 low pathogenicity avian influenza (LPAI) viruses 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-week old white le...

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

    PubMed

    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

  18. Influenza.

    PubMed

    Labella, Angelena M; Merel, Susan E

    2013-07-01

    Influenza is a common virus whose ability to change its genetic makeup allows for disease of pandemic proportion. This article summarizes the different strains of influenza circulating in the United States for the past century, the diagnosis and treatment of influenza, as well as the different ways to prevent disease. This information will be of value to clinicians caring for patients both in the hospital and in the community. PMID:23809717

  19. The East Jakarta Project: surveillance for highly pathogenic avian influenza A(H5N1) and seasonal influenza viruses in patients seeking care for respiratory disease, Jakarta, Indonesia, October 2011-September 2012.

    PubMed

    Storms, A D; Kusriastuti, R; Misriyah, S; Praptiningsih, C Y; Amalya, M; Lafond, K E; Samaan, G; Triada, R; Iuliano, A D; Ester, M; Sidjabat, R; Chittenden, K; Vogel, R; Widdowson, M A; Mahoney, F; Uyeki, T M

    2015-12-01

    Indonesia has reported the most human infections with highly pathogenic avian influenza (HPAI) A(H5N1) virus worldwide. We implemented enhanced surveillance in four outpatient clinics and six hospitals for HPAI H5N1 and seasonal influenza viruses in East Jakarta district to assess the public health impact of influenza in Indonesia. Epidemiological and clinical data were collected from outpatients with influenza-like illness (ILI) and hospitalized patients with severe acute respiratory infection (SARI); respiratory specimens were obtained for influenza testing by real-time reverse transcription-polymerase chain reaction. During October 2011-September 2012, 1131/3278 specimens from ILI cases (34·5%) and 276/1787 specimens from SARI cases (15·4%) tested positive for seasonal influenza viruses. The prevalence of influenza virus infections was highest during December-May and the proportion testing positive was 76% for ILI and 36% for SARI during their respective weeks of peak activity. No HPAI H5N1 virus infections were identified, including hundreds of ILI and SARI patients with recent poultry exposures, whereas seasonal influenza was an important contributor to acute respiratory disease in East Jakarta. Overall, 668 (47%) of influenza viruses were influenza B, 384 (27%) were A(H1N1)pdm09, and 359 (25%) were H3. While additional data over multiple years are needed, our findings suggest that seasonal influenza prevention efforts, including influenza vaccination, should target the months preceding the rainy season. PMID:25912029

  20. 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.

  1. 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.

  2. New reassortant H5N8 highly pathogenic avian influenza virus from waterfowl in Southern China

    PubMed Central

    Song, Yafen; Cui, Jin; Song, Hui; Ye, Jiaqi; Zhao, Zhishan; Wu, Siyu; Xu, Chenggang; Jiao, Peirong; Liao, Ming

    2015-01-01

    New reassortant H5N8 highly pathogenic avian influenza viruses were isolated from waterfowl in Southern China. Blast analysis demonstrated that the PB2 gene in these viruses were most closely related to A/wild duck/Shangdong/628/2011 (H5N1), while their NP genes were both more closely related to A/wild duck/Shandong/1/2011 (H5N1) and A/duck/Jiangsu/k1203/2010 (H5N8). However, the HA, NA, PB1, PA, M, and NS genes had the highest identity with A/duck/Jiangsu/k1203/2010 (H5N8). Phylogenetic analysis revealed that their HA genes belonged to the same GsGd H5 clade 2.3.4.4 detected in China in 2010. Therefore, we supposed that these H5N8 viruses might be novel reassortant viruses that have a H5N8 backbone while acquiring PB2 and NP genes from H5N1 viruses. This study is useful for better understanding the genetic and antigenic evolution of H5 avian influenza viruses in Southern China. PMID:26557113

  3. Distribution and dynamics of risk factors associated with highly pathogenic avian influenza H5N1

    PubMed Central

    Zhang, L.; Guo, Z. W.; Bridge, E. S.; Li, Y. M.; Xiao, X. M.

    2016-01-01

    SUMMARY Within China’s Poyang Lake region, close interactions between wild migratory birds and domestic poultry are common and provide an opportunity for the transmission and subsequent outbreaks of highly pathogenic avian influenza (HPAI) virus. We overlaid a series of ecological factors associated with HPAI to map the risk of HPAI in relation to natural and anthropogenic variables, and we identified two hotspots for potential HPAI outbreaks in the Poyang Lake region as well as three corridors connecting the two hotspot areas. In hotspot I, there is potential for migratory birds to bring new avian influenza (AI) strains that can reassort with existing strains to form new AI viruses. Hotspot II features high-density poultry production where outbreaks of endemic AI viruses are likely. The three communication corridors that link the two hotspots further promote HPAI H5N1 transmission and outbreaks and lead to the persistence of AI viruses in the Poyang Lake region. We speculate that the region’s unevenly distributed poultry supply-and-demand system might be a key factor inducing HPAI H5N1 transmission and outbreaks in the Poyang Lake region. PMID:23398949

  4. The Transmissibility of Highly Pathogenic Avian Influenza in Commercial Poultry in Industrialised Countries

    PubMed Central

    Garske, Tini; Clarke, Paul; Ghani, Azra C.

    2007-01-01

    Background With the increased occurrence of outbreaks of H5N1 worldwide there is concern that the virus could enter commercial poultry farms with severe economic consequences. Methodology/Principal Findings We analyse data from four recent outbreaks of highly pathogenic avian influenza (HPAI) in commercial poultry to estimate the farm-to-farm reproductive number for HPAI. The reproductive number is a key measure of the transmissibility of HPAI at the farm level because it can be used to evaluate the effectiveness of the control measures. In these outbreaks the mean farm-to-farm reproductive number prior to controls ranged from 1.1 to 2.4, with the maximum farm-based reproductive number in the range 2.2 to 3.2. Enhanced bio-security, movement restrictions and prompt isolation of the infected farms in all four outbreaks substantially reduced the reproductive number, but it remained close to the threshold value 1 necessary to ensure the disease will be eradicated. Conclusions/Significance Our results show that depending on the particular situation in which an outbreak of avian influenza occurs, current controls might not be enough to eradicate the disease, and therefore a close monitoring of the outbreak is required. The method we used for estimating the reproductive number is straightforward to implement and can be used in real-time. It therefore can be a useful tool to inform policy decisions. PMID:17406673

  5. Interspecies transmission and limited persistence of low pathogenic avian influenza genomes among Alaska dabbling ducks

    USGS Publications Warehouse

    Reeves, Andrew B.; Pearce, John M.; Ramey, Andy M.; Meixell, Brandt; Runstadler, Jonathan A.

    2011-01-01

    The reassortment and geographic distribution of low pathogenic avian influenza (LPAI) virus genes are well documented, but little is known about the persistence of intact LPAI genomes among species and locations. To examine persistence of entire LPAI genome constellations in Alaska, we calculated the genetic identities among 161 full-genome LPAI viruses isolated across 4 years from five species of duck: northern pintail (Anas acuta), mallard (Anas platyrhynchos), American green-winged teal (Anas crecca), northern shoveler (Anas clypeata) and American wigeon (Anas Americana). Based on pairwise genetic distance, highly similar LPAI genomes (>99 percent identity) were observed within and between species and across a range of geographic distances (up to and >1000 km), but most often between isolates collected 0-10 km apart. Highly similar viruses were detected between years, suggesting inter-annual persistence, but these were rare in our data set with the majority occurring within 0-9 days of sampling. These results identify LPAI transmission pathways in the context of species, space and time, an initial perspective into the extent of regional virus distribution and persistence, and insight into why no completely Eurasian genomes have ever been detected in Alaska. Such information will be useful in forecasting the movement of foreign-origin avian influenza strains should they be introduced to North America.

  6. Interspecies transmission and limited persistence of low pathogenic avian influenza genomes among Alaska dabbling ducks

    USGS Publications Warehouse

    Reeves, A.B.; Pearce, J.M.; Ramey, A.M.; Meixell, B.W.; Runstadler, J.A.

    2011-01-01

    The reassortment and geographic distribution of low pathogenic avian influenza (LPAI) virus genes are well documented, but little is known about the persistence of intact LPAI genomes among species and locations. To examine persistence of entire LPAI genome constellations in Alaska, we calculated the genetic identities among 161 full-genome LPAI viruses isolated across 4. years from five species of duck: northern pintail (Anas acuta), mallard (Anas platyrhynchos), American green-winged teal (Anas crecca), northern shoveler (Anas clypeata) and American wigeon (Anas americana). Based on pairwise genetic distance, highly similar LPAI genomes (>99% identity) were observed within and between species and across a range of geographic distances (up to and >1000 km), but most often between isolates collected 0-10. km apart. Highly similar viruses were detected between years, suggesting inter-annual persistence, but these were rare in our data set with the majority occurring within 0-9. days of sampling. These results identify LPAI transmission pathways in the context of species, space and time, an initial perspective into the extent of regional virus distribution and persistence, and insight into why no completely Eurasian genomes have ever been detected in Alaska. Such information will be useful in forecasting the movement of foreign-origin avian influenza strains should they be introduced to North America. ?? 2011.

  7. Distribution and dynamics of risk factors associated with highly pathogenic avian influenza H5N1.

    PubMed

    Zhang, L; Guo, Z W; Bridge, E S; Li, Y M; Xiao, X M

    2013-11-01

    Within China's Poyang Lake region, close interactions between wild migratory birds and domestic poultry are common and provide an opportunity for the transmission and subsequent outbreaks of highly pathogenic avian influenza (HPAI) virus. We overlaid a series of ecological factors associated with HPAI to map the risk of HPAI in relation to natural and anthropogenic variables, and we identified two hotspots for potential HPAI outbreaks in the Poyang Lake region as well as three corridors connecting the two hotspot areas. In hotspot I, there is potential for migratory birds to bring new avian influenza (AI) strains that can reassort with existing strains to form new AI viruses. Hotspot II features high-density poultry production where outbreaks of endemic AI viruses are likely. The three communication corridors that link the two hotspots further promote HPAI H5N1 transmission and outbreaks and lead to the persistence of AI viruses in the Poyang Lake region. We speculate that the region's unevenly distributed poultry supply-and-demand system might be a key factor inducing HPAI H5N1 transmission and outbreaks in the Poyang Lake region. PMID:23398949

  8. H7N9 and other pathogenic avian influenza viruses elicit a three-pronged transcriptomic signature that is reminiscent of 1918 influenza virus and is associated with lethal outcome in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Modulating the host response is a promising approach to treating influenza, a virus whose pathogenesis is determined in part by the host response it elicits. Though the pathogenicity of emerging H7N9 influenza virus has been reported in several animal models, these studies have not included a detai...

  9. Detection and prevention of highly pathogenic avian influenza in communities with high poultry disease burdens.

    PubMed

    Cardona, Carol J; Byarugaba, Denis; Mbuthia, Paul; Aning, George; Sourou, Sabi; Bunn, David A; Msoffe, Peter L

    2010-03-01

    The implementation of strategies to detect, prevent, and control highly pathogenic avian influenza (HPAI) in developing countries presents several challenges, one of which is the presence of other diseases in poultry populations. Training workshops in developing countries using the Avian Flu School have revealed that in areas with heavy Newcastle disease burdens, smallholder poultry keepers do not recognize HPAI as an immediate threat. We have developed a strategy to address the more proximal needs and priorities of communities with free-ranging poultry flocks as a means to create value in poultry, and thus to improve disease detection and prevention overall. To this end, we have created the Poultry Health and Well-Being for Development project, which trains graduate veterinarians and paraprofessionals in poultry disease diagnosis, control, and treatment. These trainees then serve their local communities to improve poultry health and to implement disease detection and management programs. PMID:20521727

  10. Poultry raising systems and highly pathogenic avian influenza outbreaks in Thailand: the situation, associations, and impacts.

    PubMed

    Chantong, Wasan; Kaneene, John B

    2011-05-01

    Highly pathogenic avian influenza (HPAI), caused by the virus strain H5N1, currently occurs worldwide with the greatest burden in Southeast Asia where the disease was first reported. In Thailand where the disease was first confirmed in January 2004, the virus had been persistent as a major threat to the poultry industry and human health over the past several years. It was generally hypothesized that the main reason for the disease to circulate in Thailand was the existence of traditional backyard chickens and free-range ducks raising systems. Consequently, this study reviewed the structure of poultry raising systems, the recent outbreaks of HPAI H5N1, the disease association to the backyard and free-grazing poultry production, and consequences of the outbreaks in Thailand. Although the major outbreaks in the country had declined, the sustaining disease surveillance and prevention are still strongly recommended. PMID:21706938

  11. Neuropathogenesis of a highly pathogenic avian influenza virus (H7N1) in experimentally infected chickens

    PubMed Central

    2011-01-01

    In order to understand the mechanism of neuroinvasion of a highly pathogenic avian influenza virus (HPAIV) into the central nervous system (CNS) of chickens, specific pathogen free chickens were inoculated with a H7N1 HPAIV. Blood, cerebrospinal fluid (CSF), nasal cavity and brain tissue samples were obtained from 1 to 4 days post-inoculation (dpi) of infected and control chickens. Viral antigen topographical distribution, presence of influenza A virus receptors in the brain, as well as, the role of the olfactory route in virus CNS invasion were studied using different immunohistochemistry techniques. Besides, viral RNA load in CSF and blood was quantified by means of a quantitative real-time reverse transcription-polymerase chain reaction. Viral antigen was observed widely distributed in the CNS, showing bilateral and symmetrical distribution in the nuclei of the diencephalon, mesencephalon and rhombencephalon. Viral RNA was detected in blood and CSF at one dpi, indicating that the virus crosses the blood-CSF-barrier early during infection. This early dissemination is possibly favoured by the presence of Siaα2,3 Gal and Siaα2,6 Gal receptors in brain vascular endothelial cells, and Siaα2,3 Gal receptors in ependymal and choroid plexus cells. No viral antigen was observed in olfactory sensory neurons, while the olfactory bulb showed only weak staining, suggesting that the virus did not use this pathway to enter into the brain. The sequence of virus appearance and the topographical distribution of this H7N1 HPAIV indicate that the viral entry occurs via the haematogenous route, with early and generalized spreading through the CSF. PMID:21982125

  12. Controlling highly pathogenic avian influenza outbreaks: An epidemiological and economic model analysis.

    PubMed

    Backer, J A; van Roermund, H J W; Fischer, E A J; van Asseldonk, M A P M; Bergevoet, R H M

    2015-09-01

    Outbreaks of highly pathogenic avian influenza (HPAI) can cause large losses for the poultry sector and for animal disease controlling authorities, as well as risks for animal and human welfare. In the current simulation approach epidemiological and economic models are combined to compare different strategies to control highly pathogenic avian influenza in Dutch poultry flocks. Evaluated control strategies are the minimum EU strategy (i.e., culling of infected flocks, transport regulations, tracing and screening of contact flocks, establishment of protection and surveillance zones), and additional control strategies comprising pre-emptive culling of all susceptible poultry flocks in an area around infected flocks (1 km, 3 km and 10 km) and emergency vaccination of all flocks except broilers around infected flocks (3 km). Simulation results indicate that the EU strategy is not sufficient to eradicate an epidemic in high density poultry areas. From an epidemiological point of view, this strategy is the least effective, while pre-emptive culling in 10 km radius is the most effective of the studied strategies. But these two strategies incur the highest costs due to long duration (EU strategy) and large-scale culling (pre-emptive culling in 10 km radius). Other analysed pre-emptive culling strategies (i.e., in 1 km and 3 km radius) are more effective than the analysed emergency vaccination strategy (in 3 km radius) in terms of duration and size of the epidemics, despite the assumed optimistic vaccination capacity of 20 farms per day. However, the total costs of these strategies differ only marginally. Extending the capacity for culling substantially reduces the duration, size and costs of the epidemic. This study demonstrates the strength of combining epidemiological and economic model analysis to gain insight in a range of consequences and thus to serve as a decision support tool in the control of HPAI epidemics. PMID:26087887

  13. 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

  14. 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

  15. New approach to delist highly pathogenic avian influenza viruses from BSL3+ select agents to BSL2 non-select status for diagnostics and vaccines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Highly pathogenic avian influenza viruses (AIV) are Select Agents in the United States and are required to be handled in bio-containment level 3 enhanced (BSL3+) facilities. Using a reverse genetics system, we attenuated a highly pathogenic virus with the goal of making it low pathogenic and having...

  16. Differences in innate immune responses to H5N1 highly pathogenic avian influenza virus infection between Pekin, Muscovy and Mallard ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ducks have been implicated in the dissemination and evolution of H5N1 highly pathogenic avian influenza (HPAI) viruses. However, differences in pathogenicity and response to vaccination have been observed between different duck species. In this study we examined the pathogenicity of H5N1 HPAI viru...

  17. 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...

  18. Growth and Pathogenic Potential of Naturally Selected Reassortants after Coinfection with Pandemic H1N1 and Highly Pathogenic Avian Influenza H5N1 Viruses

    PubMed Central

    Song, Min-Suk; Baek, Yun Hee; Pascua, Philippe Noriel Q.; Kwon, Hyeok-il; Kim, Eun-Ha; Park, Su-Jin; Kim, Se Mi; Kim, Young-Il; Choi, Won-Suk; Kim, Eung-Gook; Kim, Chul-Joong

    2015-01-01

    Coinfection of ferrets with H5N1 and pH1N1 viruses resulted in two predominate genotypes in the lungs containing surface genes of highly pathogenic avian influenza H5N1 virus in the backbone of pandemic H1N1 2009 (pH1N1). Compared to parental strains, these reassortants exhibited increased growth and virulence in vitro and in mice but failed to be transmitted indirectly to naive contact ferrets. Thus, this demonstrates a possible natural reassortment following coinfection as well as the pathogenicity of the potential reassortants. PMID:26491154

  19. Growth and Pathogenic Potential of Naturally Selected Reassortants after Coinfection with Pandemic H1N1 and Highly Pathogenic Avian Influenza H5N1 Viruses.

    PubMed

    Song, Min-Suk; Baek, Yun Hee; Pascua, Philippe Noriel Q; Kwon, Hyeok-Il; Kim, Eun-Ha; Park, Su-Jin; Kim, Se Mi; Kim, Young-Il; Choi, Won-Suk; Kim, Eung-Gook; Kim, Chul-Joong; Choi, Young Ki

    2016-01-01

    Coinfection of ferrets with H5N1 and pH1N1 viruses resulted in two predominate genotypes in the lungs containing surface genes of highly pathogenic avian influenza H5N1 virus in the backbone of pandemic H1N1 2009 (pH1N1). Compared to parental strains, these reassortants exhibited increased growth and virulence in vitro and in mice but failed to be transmitted indirectly to naive contact ferrets. Thus, this demonstrates a possible natural reassortment following coinfection as well as the pathogenicity of the potential reassortants. PMID:26491154

  20. 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.

  1. Evidence of Infection by H5N2 Highly Pathogenic Avian Influenza Viruses in Healthy Wild Waterfowl

    PubMed Central

    Hammoumi, Saliha; Newman, Scott H.; Hagemeijer, Ward; Takekawa, John Y.; Cappelle, Julien; Dodman, Tim; Joannis, Tony; Gil, Patricia; Monne, Isabella; Fusaro, Alice; Capua, Ilaria; Manu, Shiiwuua; Micheloni, Pierfrancesco; Ottosson, Ulf; Mshelbwala, John H.; Lubroth, Juan; Domenech, Joseph; Monicat, François

    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. PMID:18704172

  2. Epidemiology and ecology of highly pathogenic avian influenza with particular emphasis on South East Asia.

    PubMed

    Martin, V; Sims, L; Lubroth, J; Pfeiffer, D; Slingenbergh, J; Domenech, J

    2006-01-01

    Highly pathogenic avian influenza (HPAI) has been recognised as a serious viral disease of poultry since 1878. The number of recorded outbreaks of HPAI has increased globally in the past 10 years culminating in 2004 with the unprecedented outbreaks of H5N1 HPAI involving at least nine countries in East and South-East Asia. Apart from the geographical extent of these outbreaks and apparent rapid spread, this epidemic has a number of unique features, among which is the role that asymptomatic domestic waterfowl and more particularly free-ranging ducks play in the transmission of highly pathogenic H5N1. Field epidemiological studies have been conducted by the Food and Agriculture Organization and several collaborative centres to explore the factors that could have led to a change from infection to the emergence of widespread disease in 2003-2004 and 2005. Domestic waterfowl, specific farming practices and agro-ecological environments have been identified to play a key role in the occurrence, maintenance and spread of HPAI. Although there are some questions that remain unanswered regarding the origins of the 2004 outbreaks, the current understanding of the ecology and epidemiology of the disease should now lead to the development of adapted targeted surveillance studies and control strategies. PMID:16447491

  3. Respiratory virus is a real pathogen in immunocompetent community-acquired pneumonia: comparing to influenza like illness and volunteer controls

    PubMed Central

    2014-01-01

    Background Viral pathogens were more commonly reported than previously estimated in community-acquired pneumonia (CAP) patients. However, the real role of virus was still controversial. Methods Consecutive adult patients with CAP between April and December, 2009 were prospectively enrolled. A four-fold or greater increase of IgG-titres against respiratory viruses in pair sera was tested by means of hemagglutination inhibition assay or indirect immunofluorescence. Swab samples were tested by cell culture and/or nucleic amplification tests. Viral etiology was considered definitive if at least one of the above tests was positive. Results Viral etiology was established in fifty-two (34.9%) of 149 CAP patients, twenty-two (81.5%) of 27 influenza like illness patients, and none of 75 volunteer controls. Forty-seven CAP patients were infected by a single virus (24 influenza A virus, 5 influenza B, 10 parainfluenza virus type 3 [PIV-3], 2 PIV-1, 2 adenovirus, 2 human rhinovirus and 2 coronavirus OC43), five cases by two or three viruses co-infection. Fever ≥ 39°C (66.7%), fatigue (64.6%), and purulent sputum (52.1%) was the most common symptoms in viral pneumonia patients. On multivariate analysis, myalgia was included in the model for pneumonia associated with influenza infection. In the CURB-65 model only influenza infection was found independently associated with severe disease (CURB-65 score ≥ 3) out of variables, including age(years), sex, current smoking status, sick contact with febrile patients, numbers of comorbidity, presence of influenza infection, presence of PIV infection, with P = 0.021, OR 7.86 (95% CI 1.37-45.04). Conclusion Respiratory virus was not a bystander, but pathogenic in pneumonia and was a common cause of CAP. PMID:25178477

  4. Influenza

    PubMed Central

    2009-01-01

    Introduction During the autumn-winter months (influenza seasons), influenza circulates more frequently, causing a greater proportion of influenza-like illness, and sometimes serious seasonal epidemics. The incidence of infection depends on the underlying immunity of the population. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of vaccines to prevent influenza? What are the effects of antiviral chemoprophylaxis of influenza? What are the effects of antiviral medications to treat influenza? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2008 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 21 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: vaccines, amantadine, oseltamivir, zanamivir, rimantadine. PMID:19445759

  5. Characterizing wild bird contact and seropositivity to highly pathogenic avian influenza A (H5N1) virus in Alaskan residents

    PubMed Central

    Reed, Carrie; Bruden, Dana; Byrd, Kathy K; Veguilla, Vic; Bruce, Michael; Hurlburt, Debby; Wang, David; Holiday, Crystal; Hancock, Kathy; Ortiz, Justin R; Klejka, Joe; Katz, Jacqueline M; Uyeki, Timothy M

    2014-01-01

    Background Highly pathogenic avian influenza A (HPAI) H5N1 viruses have infected poultry and wild birds on three continents with more than 600 reported human cases (59% mortality) since 2003. Wild aquatic birds are the natural reservoir for avian influenza A viruses, and migratory birds have been documented with HPAI H5N1 virus infection. Since 2005, clade 2.2 HPAI H5N1 viruses have spread from Asia to many countries. Objectives We conducted a cross-sectional seroepidemiological survey in Anchorage and western Alaska to identify possible behaviors associated with migratory bird exposure and measure seropositivity to HPAI H5N1. Methods We enrolled rural subsistence bird hunters and their families, urban sport hunters, wildlife biologists, and a comparison group without bird contact. We interviewed participants regarding their exposures to wild birds and collected blood to perform serologic testing for antibodies against a clade 2.2 HPAI H5N1 virus strain. Results Hunters and wildlife biologists reported exposures to wild migratory birds that may confer risk of infection with avian influenza A viruses, although none of the 916 participants had evidence of seropositivity to HPAI H5N1. Conclusions We characterized wild bird contact among Alaskans and behaviors that may influence risk of infection with avian influenza A viruses. Such knowledge can inform surveillance and risk communication surrounding HPAI H5N1 and other influenza viruses in a population with exposure to wild birds at a crossroads of intercontinental migratory flyways. PMID:24828535

  6. Model-based evaluation of highly and low pathogenic avian influenza dynamics in wild birds

    USGS Publications Warehouse

    Hénaux, Viviane; Samuel, Michael D.; Bunck, Christine M.

    2010-01-01

    There is growing interest in avian influenza (AI) epidemiology to predict disease risk in wild and domestic birds, and prevent transmission to humans. However, understanding the epidemic dynamics of highly pathogenic (HPAI) viruses remains challenging because they have rarely been detected in wild birds. We used modeling to integrate available scientific information from laboratory and field studies, evaluate AI dynamics in individual hosts and waterfowl populations, and identify key areas for future research. We developed a Susceptible-Exposed-Infectious-Recovered (SEIR) model and used published laboratory challenge studies to estimate epidemiological parameters (rate of infection, latency period, recovery and mortality rates), considering the importance of age classes, and virus pathogenicity. Infectious contact leads to infection and virus shedding within 1–2 days, followed by relatively slower period for recovery or mortality. We found a shorter infectious period for HPAI than low pathogenic (LP) AI, which may explain that HPAI has been much harder to detect than LPAI during surveillance programs. Our model predicted a rapid LPAI epidemic curve, with a median duration of infection of 50–60 days and no fatalities. In contrast, HPAI dynamics had lower prevalence and higher mortality, especially in young birds. Based on field data from LPAI studies, our model suggests to increase surveillance for HPAI in post-breeding areas, because the presence of immunologically naïve young birds is predicted to cause higher HPAI prevalence and bird losses during this season. Our results indicate a better understanding of the transmission, infection, and immunity-related processes is required to refine predictions of AI risk and spread, improve surveillance for HPAI in wild birds, and develop disease control strategies to reduce potential transmission to domestic birds and/or humans.

  7. Highly Pathogenic Influenza A(H5N1) Virus Survival in Complex Artificial Aquatic Biotopes

    PubMed Central

    Horm, Viseth Srey; Gutiérrez, Ramona A.; Nicholls, John M.; Buchy, Philippe

    2012-01-01

    Background Very little is known regarding the persistence of Highly Pathogenic Avian Influenza (HPAI) H5N1 viruses in aquatic environments in tropical countries, although environmental materials have been suggested to play a role as reservoirs and sources of transmission for H5N1 viruses. Methodology/Principal Findings The survival of HPAI H5N1 viruses in experimental aquatic biotopes (water, mud, aquatic flora and fauna) relevant to field conditions in Cambodia was investigated. Artificial aquatic biotopes, including simple ones containing only mud and water, and complex biotopes involving the presence of aquatic flora and fauna, were set up. They were experimentally contaminated with H5N1 virus. The persistence of HPAI H5N1 virus (local avian and human isolates) was determined by virus isolation in embryonated chicken eggs and by real-time reverse-polymerase chain reaction. Persistence of infectious virus did not exceed 4 days, and was only identified in rain water. No infectious virus particles were detected in pond and lake water or mud even when high inoculum doses were used. However, viral RNA persisted up to 20 days in rain water and 7 days in pond or lake water. Viral RNA was also detected in mud samples, up to 14 days post-contamination in several cases. Infectious virus and viral RNA was detected in few cases in the aquatic fauna and flora, especially in bivalves and labyrinth fish, although these organisms seemed to be mostly passive carriers of the virus rather than host allowing virus replication. Conclusions/Significance Although several factors for the survival and persistence of HPAI viruses in the environment are still to be elucidated, and are particularly hard to control in laboratory conditions, our results, along with previous data, support the idea that environmental surveillance is of major relevance for avian influenza control programs. PMID:22514622

  8. Intersubtype Reassortments of H5N1 Highly Pathogenic Avian Influenza Viruses Isolated from Quail.

    PubMed

    Nguyen, Tinh Huu; Than, Van Thai; Thanh, Hien Dang; Hung, Vu-Khac; Nguyen, Duc Tan; Kim, Wonyong

    2016-01-01

    H5N1 highly pathogenic avian influenza (HPAI) viruses are considered a threat to national animal industries, causing production losses and high mortality in domestic poultry. In recent years, quail has become a popular terrestrial poultry species raised for production of meat and eggs in Asia. In this study, to better understand the roles of quail in H5N1 viral evolution, two H5N1-positive samples, designated A/quail/Vietnam/CVVI-49/2010 (CVVI-49/2010) and A/quail/Vietnam/CVVI-50/2014 (CVVI-50/2014), were isolated from quail during H5N1 outbreaks in Vietnam, and their whole genome were analyzed. The phylogenetic analysis reveals new evolutionary variation in the worldwide H5N1 viruses. The quail HA genes were clustered into clades 1.1.1 (CVVI-49/2010) and clade 2.3.2.1c (CVVI-50/2014), which may have evolved from viruses circulating from chickens and/or ducks in Cambodia, mainland of China, Taiwan, Indonesia, and South Korea in recent years. Interestingly, the M2 gene of the CVVI-49/2010 strain contained amino acid substitutions at position 26L-I and 31S-N that are related to amantadine-resistance. In particular, the CVVI-50/2014 strain revealed evidence of multiple intersubtype reassortment events between virus clades 2.3.2.1c, 2.3.2.1b, and 2.3.2.1a. Data from this study supports the possible role of quail as an important intermediate host in avian influenza virus evolution. Therefore, additional surveillance is needed to monitor these HPAI viruses both serologically and virologically in quail. PMID:26900963

  9. Evolutionary Analysis of Inter-Farm Transmission Dynamics in a Highly Pathogenic Avian Influenza Epidemic

    PubMed Central

    Bataille, Arnaud; van der Meer, Frank; Stegeman, Arjan; Koch, Guus

    2011-01-01

    Phylogenetic studies have largely contributed to better understand the emergence, spread and evolution of highly pathogenic avian influenza during epidemics, but sampling of genetic data has never been detailed enough to allow mapping of the spatiotemporal spread of avian influenza viruses during a single epidemic. Here, we present genetic data of H7N7 viruses produced from 72% of the poultry farms infected during the 2003 epidemic in the Netherlands. We use phylogenetic analyses to unravel the pathways of virus transmission between farms and between infected areas. In addition, we investigated the evolutionary processes shaping viral genetic diversity, and assess how they could have affected our phylogenetic analyses. Our results show that the H7N7 virus was characterized by a high level of genetic diversity driven mainly by a high neutral substitution rate, purifying selection and limited positive selection. We also identified potential reassortment in the three genes that we have tested, but they had only a limited effect on the resolution of the inter-farm transmission network. Clonal sequencing analyses performed on six farm samples showed that at least one farm sample presented very complex virus diversity and was probably at the origin of chronological anomalies in the transmission network. However, most virus sequences could be grouped within clearly defined and chronologically sound clusters of infection and some likely transmission events between farms located 0.8–13 Km apart were identified. In addition, three farms were found as most likely source of virus introduction in distantly located new areas. These long distance transmission events were likely facilitated by human-mediated transport, underlining the need for strict enforcement of biosafety measures during outbreaks. This study shows that in-depth genetic analysis of virus outbreaks at multiple scales can provide critical information on virus transmission dynamics and can be used to increase

  10. Intersubtype Reassortments of H5N1 Highly Pathogenic Avian Influenza Viruses Isolated from Quail

    PubMed Central

    Nguyen, Tinh Huu; Than, Van Thai; Thanh, Hien Dang; Hung, Vu-Khac; Nguyen, Duc Tan; Kim, Wonyong

    2016-01-01

    H5N1 highly pathogenic avian influenza (HPAI) viruses are considered a threat to national animal industries, causing production losses and high mortality in domestic poultry. In recent years, quail has become a popular terrestrial poultry species raised for production of meat and eggs in Asia. In this study, to better understand the roles of quail in H5N1 viral evolution, two H5N1-positive samples, designated A/quail/Vietnam/CVVI-49/2010 (CVVI-49/2010) and A/quail/Vietnam/CVVI-50/2014 (CVVI-50/2014), were isolated from quail during H5N1 outbreaks in Vietnam, and their whole genome were analyzed. The phylogenetic analysis reveals new evolutionary variation in the worldwide H5N1 viruses. The quail HA genes were clustered into clades 1.1.1 (CVVI-49/2010) and clade 2.3.2.1c (CVVI-50/2014), which may have evolved from viruses circulating from chickens and/or ducks in Cambodia, mainland of China, Taiwan, Indonesia, and South Korea in recent years. Interestingly, the M2 gene of the CVVI-49/2010 strain contained amino acid substitutions at position 26L-I and 31S-N that are related to amantadine-resistance. In particular, the CVVI-50/2014 strain revealed evidence of multiple intersubtype reassortment events between virus clades 2.3.2.1c, 2.3.2.1b, and 2.3.2.1a. Data from this study supports the possible role of quail as an important intermediate host in avian influenza virus evolution. Therefore, additional surveillance is needed to monitor these HPAI viruses both serologically and virologically in quail. PMID:26900963

  11. Genetically Diverse Low Pathogenicity Avian Influenza A Virus Subtypes Co-Circulate among Poultry in Bangladesh.

    PubMed

    Gerloff, Nancy A; Khan, Salah Uddin; Zanders, Natosha; Balish, Amanda; Haider, Najmul; Islam, Ausraful; Chowdhury, Sukanta; Rahman, Mahmudur Ziaur; Haque, Ainul; Hosseini, Parviez; Gurley, Emily S; Luby, Stephen P; Wentworth, David E; Donis, Ruben O; Sturm-Ramirez, Katharine; Davis, C Todd

    2016-01-01

    Influenza virus surveillance, poultry outbreak investigations and genomic sequencing were assessed to understand the ecology and evolution of low pathogenicity avian influenza (LPAI) A viruses in Bangladesh from 2007 to 2013. We analyzed 506 avian specimens collected from poultry in live bird markets and backyard flocks to identify influenza A viruses. Virus isolation-positive specimens (n = 50) were subtyped and their coding-complete genomes were sequenced. The most frequently identified subtypes among LPAI isolates were H9N2, H11N3, H4N6, and H1N1. Less frequently detected subtypes included H1N3, H2N4, H3N2, H3N6, H3N8, H4N2, H5N2, H6N1, H6N7, and H7N9. Gene sequences were compared to publicly available sequences using phylogenetic inference approaches. Among the 14 subtypes identified, the majority of viral gene segments were most closely related to poultry or wild bird viruses commonly found in Southeast Asia, Europe, and/or northern Africa. LPAI subtypes were distributed over several geographic locations in Bangladesh, and surface and internal protein gene segments clustered phylogenetically with a diverse number of viral subtypes suggesting extensive reassortment among these LPAI viruses. H9N2 subtype viruses differed from other LPAI subtypes because genes from these viruses consistently clustered together, indicating this subtype is enzootic in Bangladesh. The H9N2 strains identified in Bangladesh were phylogenetically and antigenically related to previous human-derived H9N2 viruses detected in Bangladesh representing a potential source for human infection. In contrast, the circulating LPAI H5N2 and H7N9 viruses were both phylogenetically and antigenically unrelated to H5 viruses identified previously in humans in Bangladesh and H7N9 strains isolated from humans in China. In Bangladesh, domestic poultry sold in live bird markets carried a wide range of LPAI virus subtypes and a high diversity of genotypes. These findings, combined with the seven year

  12. Genetically Diverse Low Pathogenicity Avian Influenza A Virus Subtypes Co-Circulate among Poultry in Bangladesh

    PubMed Central

    Gerloff, Nancy A.; Khan, Salah Uddin; Zanders, Natosha; Balish, Amanda; Haider, Najmul; Islam, Ausraful; Chowdhury, Sukanta; Rahman, Mahmudur Ziaur; Haque, Ainul; Hosseini, Parviez; Gurley, Emily S.; Luby, Stephen P.; Wentworth, David E.; Donis, Ruben O.; Sturm-Ramirez, Katharine; Davis, C. Todd

    2016-01-01

    Influenza virus surveillance, poultry outbreak investigations and genomic sequencing were assessed to understand the ecology and evolution of low pathogenicity avian influenza (LPAI) A viruses in Bangladesh from 2007 to 2013. We analyzed 506 avian specimens collected from poultry in live bird markets and backyard flocks to identify influenza A viruses. Virus isolation-positive specimens (n = 50) were subtyped and their coding-complete genomes were sequenced. The most frequently identified subtypes among LPAI isolates were H9N2, H11N3, H4N6, and H1N1. Less frequently detected subtypes included H1N3, H2N4, H3N2, H3N6, H3N8, H4N2, H5N2, H6N1, H6N7, and H7N9. Gene sequences were compared to publicly available sequences using phylogenetic inference approaches. Among the 14 subtypes identified, the majority of viral gene segments were most closely related to poultry or wild bird viruses commonly found in Southeast Asia, Europe, and/or northern Africa. LPAI subtypes were distributed over several geographic locations in Bangladesh, and surface and internal protein gene segments clustered phylogenetically with a diverse number of viral subtypes suggesting extensive reassortment among these LPAI viruses. H9N2 subtype viruses differed from other LPAI subtypes because genes from these viruses consistently clustered together, indicating this subtype is enzootic in Bangladesh. The H9N2 strains identified in Bangladesh were phylogenetically and antigenically related to previous human-derived H9N2 viruses detected in Bangladesh representing a potential source for human infection. In contrast, the circulating LPAI H5N2 and H7N9 viruses were both phylogenetically and antigenically unrelated to H5 viruses identified previously in humans in Bangladesh and H7N9 strains isolated from humans in China. In Bangladesh, domestic poultry sold in live bird markets carried a wide range of LPAI virus subtypes and a high diversity of genotypes. These findings, combined with the seven year

  13. Surveillance for Highly Pathogenic Avian Influenza Virus in Wild Birds during Outbreaks in Domestic Poultry, Minnesota, 2015

    PubMed Central

    Carstensen, Michelle; Hildebrand, Erik C.; Cornicelli, Louis; Wolf, Paul; 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 understand the potential 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 fecal samples. PMID:27064759

  14. Pathogenicity and tissue tropism of currently circulating highly pathogenic avian influenza A virus (H5N1; clade 2.3.2) in tufted ducks (Aythya fuligula).

    PubMed

    Bröjer, Caroline; van Amerongen, Geert; van de Bildt, Marco; van Run, Peter; Osterhaus, Albert; Gavier-Widén, Dolores; Kuiken, Thijs

    2015-11-18

    Reports describing the isolation of highly pathogenic avian influenza (HPAI) virus (H5N1) clade 2.3.2 in feces from apparently healthy wild birds and the seemingly lower pathogenicity of this clade compared to clade 2.2 in several experimentally infected species, caused concern that the new clade might be maintained in the wild bird population. To investigate whether the pathogenicity of a clade 2.3.2 virus was lower than that of clades previously occurring in free-living wild birds in Europe, four tufted ducks were inoculated with influenza A/duck/HongKong/1091/2011 (H5N1) clade 2.3.2 virus. The ducks were monitored and sampled for virus excretion daily during 4 days, followed by pathologic, immunohistochemical, and virological investigations. The virus produced severe disease as evidenced by clinical signs, presence of marked lesions and abundant viral antigen in several tissues, especially the central nervous system. The study shows that HPAI-H5N1 virus clade 2.3.2 is highly pathogenic for tufted ducks and thus, they are unlikely to maintain this clade in the free-living population or serve as long-distance vectors. PMID:26441012

  15. Current status and future needs in diagnostics and vaccines for high pathogenicity avian influenza.

    PubMed

    Swayne, D E; Spackman, E

    2013-01-01

    Since 1959, 32 epizootics of high pathogenicity avian influenza (HPAI) have occurred in birds. Rapid detection and accurate identification of HPAI has been critical to controlling such epizootics in poultry. Specific paradigms for the detection and diagnosis of avian influenza virus (AIV) in poultry vary somewhat among different countries and industry compartments depending on specific needs and resources. Importantly, since HPAI and low pathogenicity (LP) AI of the H5 and H7 subtypes are reportable to the World Organization for Animal Health (OIE), diagnostic procedures are implemented for regulatory purposes and are harmonized to some degree. Most current tests are adequate and have been in use for some time, therefore they have been well validated and presently there is no reported new technology that will completely replace the current tests. However, some modifications, updates or additional tests could be beneficial. The element of AIV diagnostics that is most in need of improvement is in determining the hemagglutinin and neuraminidase subtype specificity of antibody to AIV. Most HPAI epizootics have been eradicated using traditional stamping-out programs, but beginning in 1995, five epizootics have added vaccination as an additional, interim control tool. From 2002-2010, >113 billion doses of AI vaccine have been used in poultry; 95.5% as oil-emulsified, inactivated whole AIV vaccines and 4.5% as live vectored vaccines. The majority of vaccine has been used in the four H5N1 HPAI enzootic countries (China [91%], Egypt [4.7%], Indonesia [2.3%], and Vietnam [1.4%]) where vaccination programs are directed to all poultry. The 10 other countries/regions have used less than 1% of the vaccine, administered in a focused, risk- based approach. Some vaccine "failures" have resulted from antigenic drift of field viruses away from the vaccine viruses, but most have resulted from failures in the vaccination process; i.e. failure to adequately administer the vaccine to at

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

    PubMed

    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

  18. Wind-Mediated Spread of Low-Pathogenic Avian Influenza Virus into the Environment during Outbreaks at Commercial Poultry Farms.

    PubMed

    Jonges, Marcel; van Leuken, Jeroen; Wouters, Inge; Koch, Guus; Meijer, Adam; Koopmans, Marion

    2015-01-01

    Avian influenza virus-infected poultry can release a large amount of virus-contaminated droppings that serve as sources of infection for susceptible birds. Much research so far has focused on virus spread within flocks. However, as fecal material or manure is a major constituent of airborne poultry dust, virus-contaminated particulate matter from infected flocks may be dispersed into the environment. We collected samples of suspended particulate matter, or the inhalable dust fraction, inside, upwind and downwind of buildings holding poultry infected with low-pathogenic avian influenza virus, and tested them for the presence of endotoxins and influenza virus to characterize the potential impact of airborne influenza virus transmission during outbreaks at commercial poultry farms. Influenza viruses were detected by RT-PCR in filter-rinse fluids collected up to 60 meters downwind from the barns, but virus isolation did not yield any isolates. Viral loads in the air samples were low and beyond the limit of RT-PCR quantification except for one in-barn measurement showing a virus concentration of 8.48 x 10(4) genome copies/m(3). Air samples taken outside poultry barns had endotoxin concentrations of ~50 EU/m(3) that declined with increasing distance from the barn. Atmospheric dispersion modeling of particulate matter, using location-specific meteorological data for the sampling days, demonstrated a positive correlation between endotoxin measurements and modeled particulate matter concentrations, with an R(2) varying from 0.59 to 0.88. Our data suggest that areas at high risk for human or animal exposure to airborne influenza viruses can be modeled during an outbreak to allow directed interventions following targeted surveillance. PMID:25946115

  19. Wind-Mediated Spread of Low-Pathogenic Avian Influenza Virus into the Environment during Outbreaks at Commercial Poultry Farms

    PubMed Central

    Jonges, Marcel; van Leuken, Jeroen; Wouters, Inge; Koch, Guus; Meijer, Adam; Koopmans, Marion

    2015-01-01

    Avian influenza virus-infected poultry can release a large amount of virus-contaminated droppings that serve as sources of infection for susceptible birds. Much research so far has focused on virus spread within flocks. However, as fecal material or manure is a major constituent of airborne poultry dust, virus-contaminated particulate matter from infected flocks may be dispersed into the environment. We collected samples of suspended particulate matter, or the inhalable dust fraction, inside, upwind and downwind of buildings holding poultry infected with low-pathogenic avian influenza virus, and tested them for the presence of endotoxins and influenza virus to characterize the potential impact of airborne influenza virus transmission during outbreaks at commercial poultry farms. Influenza viruses were detected by RT-PCR in filter-rinse fluids collected up to 60 meters downwind from the barns, but virus isolation did not yield any isolates. Viral loads in the air samples were low and beyond the limit of RT-PCR quantification except for one in-barn measurement showing a virus concentration of 8.48x104 genome copies/m3. Air samples taken outside poultry barns had endotoxin concentrations of ~50 EU/m3 that declined with increasing distance from the barn. Atmospheric dispersion modeling of particulate matter, using location-specific meteorological data for the sampling days, demonstrated a positive correlation between endotoxin measurements and modeled particulate matter concentrations, with an R2 varying from 0.59 to 0.88. Our data suggest that areas at high risk for human or animal exposure to airborne influenza viruses can be modeled during an outbreak to allow directed interventions following targeted surveillance. PMID:25946115

  20. The avian and mammalian host range of highly pathogenic avian H5N1 influenza

    PubMed Central

    Kaplan, Bryan S.; Webby, Richard J.

    2013-01-01

    Highly pathogenic H5N1 influenza viruses have been isolated from a number of avian and mammalian species. Despite intensive control measures the number of human and animal cases continues to increase. A more complete understanding of susceptible species and of contributing environmental and molecular factors is crucial if we are to slow the rate of new cases. H5N1 is currently endemic in domestic poultry in only a handful of countries with sporadic and unpredictable spread to other countries. Close contact of terrestrial bird or mammalian species with infected poultry/waterfowl or their biological products is the major route for interspecies transmission. Intra-species transmission of H5N1 in mammals, including humans, has taken place on a limited scale though it remains to be seen if this will change; recent laboratory studies suggest that it is indeed possible. Here we review the avian and mammalian species that are naturally susceptible to H5N1 infection and the molecular factors associated with its expanded host range. PMID:24025480

  1. New Reassortant H5N6 Highly Pathogenic Avian Influenza Viruses in Southern China, 2014.

    PubMed

    Jiao, Peirong; Cui, Jin; Song, Yafen; Song, Hui; Zhao, Zhishan; Wu, Siyu; Qu, Nannan; Wang, Nianchen; Ouyang, Guowen; Liao, Ming

    2016-01-01

    New reassortant H5N6 highly pathogenic avian influenza viruses (AIVs) were isolated from apparently healthy domestic ducks in Southern China in 2014. Our results show that the viruses grew efficiently in eggs and replicated systemically in chickens. They were completely lethal in chicken (100% mortality), and the mean death time was 6 to 7 days post-inoculation. The viruses could transmit in chickens by naïve contact. BLAST analysis revealed that their HA gene was most closely related to A/wild duck/Shangdong/628/2011 (H5N1), and their NA genes were most closely related to A/swine/Guangdong/K6/2010 (H6N6). The other genes had the highest identity with A/wild duck/Fujian/1/2011(H5N1). The results of phylogenetic analysis showed that their HA genes clustered into clade 2.3.4.4 of the H5N1 viruses and all genes derived from H5 were Mix-like or H6-like viruses. Thus, the new H5N6 viruses were reassortmented of H5N1 and H6N6 virus. Therefore, the circulation of the new H5N6 AIVs may become a threat to poultry and human health. PMID:27242767

  2. Risk factors and clusters of Highly Pathogenic Avian Influenza H5N1 outbreaks in Bangladesh

    PubMed Central

    Loth, Leo; Gilbert, Marius; Osmani, Mozaffar G.; Kalam, Abul M.; Xiao, Xiangming

    2016-01-01

    Between March 2007 and July 2009, 325 Highly Pathogenic Avian Influenza (HPAI, subtype H5N1) outbreaks in poultry were reported in 154 out of a total of 486 sub-districts in Bangladesh. This study analyzed the temporal and spatial patterns of HPAI H5N1 outbreaks and quantified the relationship between several spatial risk factors and HPAI outbreaks in sub-districts in Bangladesh. We assessed spatial autocorrelation and spatial dependence, and identified clustering sub-districts with disease statistically similar to or dissimilar from their neighbors. Three significant risk factors associated to HPAI H5N1 virus outbreaks were identified; the quadratic log-transformation of human population density [humans per square kilometer, P = 0.01, OR 1.15 (95% CI: 1.03–1.28)], the log-transformation of the total commercial poultry population [number of commercial poultry per sub-district, P < 0.002, OR 1.40 (95% CI: 1.12–1.74)], and the number of roads per sub-district [P = 0.02, OR 1.07 (95% CI: 1.01–1.14)]. The distinct clusters of HPAI outbreaks and risk factors identified could assist the Government of Bangladesh to target surveillance and to concentrate response efforts in areas where disease is likely to occur. Concentrating response efforts may help to combat HPAI more effectively, reducing the environmental viral load and so reducing the number of disease incidents. PMID:20554337

  3. Extent of antigenic cross-reactivity among highly pathogenic H5N1 influenza viruses.

    PubMed

    Ducatez, Mariette F; Cai, Zhipeng; Peiris, Malik; Guan, Yi; Ye, Zhiping; Wan, Xiu-Feng; Webby, Richard J

    2011-10-01

    Highly pathogenic H5N1 avian influenza viruses emerged in 1996 and have since evolved so extensively that a single strain can no longer be used as a prepandemic vaccine or diagnostic reagent. We therefore sought to identify the H5N1 strains that may best serve as cross-reactive diagnostic reagents. We compared the cross-reactivity of 27 viruses of clades 0, 1, 2.1, 2.2, 2.3, and 4 and of four computationally designed ancestral H5N1 strains by hemagglutination inhibition (HI) and microneutralization (MN) assays. Antigenic cartography was used to analyze the large quantity of resulting data. Cartographs of HI titers with chicken red blood cells were similar to those of MN titers, but HI with horse red blood cells decreased antigenic distances among the H5N1 strains studied. Thus, HI with horse red blood cells seems to be the assay of choice for H5N1 diagnostics. Whereas clade 2.2 antigens were able to detect antibodies raised to most of the tested H5N1 viruses (and clade 2.2-specific antisera detected most of the H5N1 antigens), ancestral strain A exhibited the widest reactivity pattern and hence was the best candidate diagnostic reagent for broad detection of H5N1 strains. PMID:21832017

  4. Low-pathogenicity H7N2 avian influenza outbreak in Virgnia during 2002.

    PubMed

    Akey, B L

    2003-01-01

    An outbreak of low-pathogenicity H7N2 avian influenza virus (AIV) in the Shenandoah Valley of Virginia during the spring and summer of 2002 affected 197 farms and resulted in the destruction of over 4.7 million birds. The outbreak affected primarily turkey farms (28 breeders, 125 grow out) with some spillover into chicken farms (29 breeders, 13 grow out, 2 table-egg layers). Although no direct link was established, the strain of H7N2 AIV in this outbreak had a molecular fingerprint that was essentially identical to the H7N2 AIV strain that has circulated in the live bird markets of the northeastern United States for the last 8 yr. After an initial delay caused by lack of viable disposal options, depopulation and disposal, primarily in sanitary landfills, was carried out within 24 hr of detection of a positive flock. Increased surveillance efforts included once-a-week testing of the daily mortality of all poultry farms in the region, testing of all breeder farms every 2 wk, and testing of all flocks prior to movement for any reason. A statistical sampling of backyard flocks and wild birds found no evidence of the virus. The successful eradication of this outbreak was the result of the efforts of a highly effective task force of industry, state, and federal personnel. PMID:14575120

  5. Identifying risk factors of highly pathogenic avian influenza (H5N1 subtype) in Indonesia

    PubMed Central

    Leo, Loth; Marius, Gilbert; Jianmei, Wu; Christina, Czarnecki; Muhammad, Hidayat; Xiangming, Xiao

    2016-01-01

    Highly pathogenic avian influenza (HPAI), subtype H5N1, was first officially reported in Indonesia in 2004. Since then the disease has spread and is now endemic in large parts of the country. This study investigated the statistical relationship between a set of risk factors and the presence or absence of HPAI in Indonesia during 2006 and 2007. HPAI was evaluated through participatory disease surveillance (PDS) in backyard village chickens (the study population), and risk factors included descriptors of people and poultry distribution (separating chickens, ducks and production sectors), poultry movement patterns and agro-ecological conditions. The study showed that the risk factors “elevation”, “human population density” and “rice cropping” were significant in accounting for the spatial variation of the PDS-defined HPAI cases. These findings were consistent with earlier studies in Thailand and Vietnam. In addition “commercial poultry population”, and two indicators of market locations and transport; “human settlements” and “road length”, were identified as significant risk factors in the models. In contrast to several previous studies carried out in Southeast Asia, domestic backyard ducks were not found to be a significant risk factor in Indonesia. The study used surrogate estimates of market locations and marketing chains and further work should focus on the actual location of the live bird markets, and on the flow of live poultry and poultry products between them, so that patterns of possible transmission, and regions of particular risk could be better inferred. PMID:21813198

  6. Assessment of the Potential Distance of Dispersal of High Pathogenicity Avian Influenza Virus by Wild Mallards.

    PubMed

    Śmietanka, Krzysztof; Bocian, Łukasz; Meissner, Włodzimierz; Ziętek-Barszcz, Anna; Żółkoś, Katarzyna

    2016-05-01

    This work presents the results of studies aimed at assessing the median and maximum distances covered by wild mallards (Anas platyrhynchos; n = 38), hypothetically infected with the high pathogenicity avian influenza virus (HPAIV) during spring migrations, using GPS-GSM tracking and published data on the susceptibility to HPAIV infection and duration of shedding. The model was based on the assumptions that the birds shed virus in the absence of clinical signs during infectious periods (IP) that were assumed to last 1 day (IP1), 4 days (IP4), and 8 days (IP8) and that each day of migration is a hypothetical day of the onset of IP. Using the haversine formula over a sliding timeframe corresponding to each IP, distances were estimated for each duck that undertook migration and then the maximum distance (Dmax) was selected. Ten mallards undertook spring migrations but, due to the loss of signal in the GPS-GSM devices, only three ducks were observed during autumn migrations. The following ranges of Dmax values were calculated for spring migrations: 124-382 km for IP1 (median 210 km), 208-632 km for IP4 (median 342 km), and 213-687 km for IP8 (median 370 km). The present study provides information that can be used as a data source to perform risk assessment related to the contribution of wild mallards in the dispersal of HPAIV over considerable distances. PMID:27309073

  7. New Reassortant H5N6 Highly Pathogenic Avian Influenza Viruses in Southern China, 2014

    PubMed Central

    Jiao, Peirong; Cui, Jin; Song, Yafen; Song, Hui; Zhao, Zhishan; Wu, Siyu; Qu, Nannan; Wang, Nianchen; Ouyang, Guowen; Liao, Ming

    2016-01-01

    New reassortant H5N6 highly pathogenic avian influenza viruses (AIVs) were isolated from apparently healthy domestic ducks in Southern China in 2014. Our results show that the viruses grew efficiently in eggs and replicated systemically in chickens. They were completely lethal in chicken (100% mortality), and the mean death time was 6 to 7 days post-inoculation. The viruses could transmit in chickens by naïve contact. BLAST analysis revealed that their HA gene was most closely related to A/wild duck/Shangdong/628/2011 (H5N1), and their NA genes were most closely related to A/swine/Guangdong/K6/2010 (H6N6). The other genes had the highest identity with A/wild duck/Fujian/1/2011(H5N1). The results of phylogenetic analysis showed that their HA genes clustered into clade 2.3.4.4 of the H5N1 viruses and all genes derived from H5 were Mix-like or H6-like viruses. Thus, the new H5N6 viruses were reassortmented of H5N1 and H6N6 virus. Therefore, the circulation of the new H5N6 AIVs may become a threat to poultry and human health. PMID:27242767

  8. H9N2 low pathogenic avian influenza in Pakistan (2012–2015)

    PubMed Central

    Lee, Dong-Hun; Swayne, David E.; Sharma, Poonam; Rehmani, Shafqat Fatima; Wajid, Abdul; Suarez, David L.; Afonso, Claudio L.

    2016-01-01

    Significant economic losses from deaths and decreased egg production have resulted from H9N2 low pathogenic avian influenza virus (LPAIV) infections in poultry across North Africa, the Middle East and Asia. The H9N2 LPAIVs have been endemic in Pakistani poultry since 1996, but no new viruses have been reported since 2010. Because novel genotypes of Pakistani H9N2 contain mammalian host-specific markers, recent surveillance is essential to better understand any continuing public health risk. Here the authors report on four new H9N2 LPAIVs, three from 2015 and one from 2012. All of the viruses tested in this study belonged to Middle East B genetic group of G1 lineage and had PAKSSR/G motif at the haemagglutinin cleavage site. The mammalian host-specific markers at position 226 in the haemagglutinin receptor-binding site and internal genes suggest that Pakistan H9N2 viruses are still potentially infectious for mammals. Continued active surveillance in poultry and mammals is needed to monitor the spread and understand the potential for zoonotic infection by these H9N2 LPAIVs. PMID:27403327

  9. Identifying risk factors of highly pathogenic avian influenza (H5N1 subtype) in Indonesia.

    PubMed

    Loth, Leo; Gilbert, Marius; Wu, Jianmei; Czarnecki, Christina; Hidayat, Muhammad; Xiao, Xiangming

    2011-10-01

    Highly pathogenic avian influenza (HPAI), subtype H5N1, was first officially reported in Indonesia in 2004. Since then the disease has spread and is now endemic in large parts of the country. This study investigated the statistical relationship between a set of risk factors and the presence or absence of HPAI in Indonesia during 2006 and 2007. HPAI was evaluated through participatory disease surveillance (PDS) in backyard village chickens (the study population), and risk factors included descriptors of people and poultry distribution (separating chickens, ducks and production sectors), poultry movement patterns and agro-ecological conditions. The study showed that the risk factors "elevation", "human population density" and "rice cropping" were significant in accounting for the spatial variation of the PDS-defined HPAI cases. These findings were consistent with earlier studies in Thailand and Vietnam. In addition "commercial poultry population", and two indicators of market locations and transport; "human settlements" and "road length", were identified as significant risk factors in the models. In contrast to several previous studies carried out in Southeast Asia, domestic backyard ducks were not found to be a significant risk factor in Indonesia. The study used surrogate estimates of market locations and marketing chains and further work should focus on the actual location of the live bird markets, and on the flow of live poultry and poultry products between them, so that patterns of possible transmission, and regions of particular risk could be better inferred. PMID:21813198

  10. [Effect of Deletion of the Carboxyl Terminal of the NS1 Protein on Pathogenicity of the Influenza B Virus].

    PubMed

    Li, Xue; Yu, Zhijun; Sun, Weiyang; Chen, Qiang; Wang, Tiecheng; Yang, Songtao; Huang, Geng; Gao, Yuwei; Xia, Xianzhu; Zhang, Xuemei

    2015-07-01

    To analyze the molecular basis of the variation of the pathogenicity of the influenza B virus, we rescued a recombinant virus with a deletion in the carboxyl terminal of the NS1 protein using reverse genetics based on the parental virus B-S9 of B/Yamagata/16/88. A mutant strain with a deletion of 171 amino acids in the carboxyl terminal of the NS1 protein was named "B-L5". BALB/c mice were inoculated with 3 X 105 EID50 of B-L5 and the parental virus B-S9, respectively. Then, weight changes, survival, and viral titers were documented. During 3 days post-inoculation (dpi) to 7 dpi, the weight of mice infected with B-S9 decreased. However, the weight of mice infected with B-L5 showed weight decreases only at 2 dpi, and quickly recovered at 3 dpi. B-S9 and B-L5 could replicate in the lungs of BALB/c mice. However, viral titers in the lungs of mice infected with B-L5 were 7900-times lower than those of mice infected with B-S9 at 3 dpi. Viral titers in the lungs of mice infected with B-L5 were not detected at 6 dpi. These results showed that, compared with the parent virus B-S9, the mutant virus B-L5 showed lower pathogenicity in BALB/c mice. Our study suggests that deletion of the carboxyl terminal of the NS1 protein decreases the pathogenicity of the influenza B virus. Establishment of a reverse-genetics system for the B influenza virus will provide a platform for studying its pathogenesis, and mechanism of transmission, and for developing live-attenuated influenza B virus vaccines. PMID:26524913

  11. Towards a universal vaccine for avian influenza: protective efficacy of modified Vaccinia virus Ankara and Adenovirus vaccines expressing conserved influenza antigens in chickens challenged with low pathogenic avian influenza virus.

    PubMed

    Boyd, Amy C; Ruiz-Hernandez, Raul; Peroval, Marylene Y; Carson, Connor; Balkissoon, Devanand; Staines, Karen; Turner, Alison V; Hill, Adrian V S; Gilbert, Sarah C; Butter, Colin

    2013-01-11

    Current vaccines targeting surface proteins can drive antigenic variation resulting either in the emergence of more highly pathogenic viruses or of antigenically distinct viruses that escape control by vaccination and thereby persist in the host population. Influenza vaccines typically target the highly mutable surface proteins and do not provide protection against heterologous challenge. Vaccines which induce immune responses against conserved influenza epitopes may confer protection against heterologous challenge. We report here the results of vaccination with recombinant modified Vaccinia virus Ankara (MVA) and Adenovirus (Ad) expressing a fusion construct of nucleoprotein and matrix protein (NP+M1). Prime and boost vaccination regimes were trialled in different ages of chicken and were found to be safe and immunogenic. Interferon-γ (IFN-γ) ELISpot was used to assess the cellular immune response post secondary vaccination. In ovo Ad prime followed by a 4 week post hatch MVA boost was identified as the most immunogenic regime in one outbred and two inbred lines of chicken. Following vaccination, one inbred line (C15I) was challenged with low pathogenic avian influenza (LPAI) H7N7 (A/Turkey/England/1977). Birds receiving a primary vaccination with Ad-NP+M1 and a secondary vaccination with MVA-NP+M1 exhibited reduced cloacal shedding as measured by plaque assay at 7 days post infection compared with birds vaccinated with recombinant viruses containing irrelevant antigen. This preliminary indication of efficacy demonstrates proof of concept in birds; induction of T cell responses in chickens by viral vectors containing internal influenza antigens may be a productive strategy for the development of vaccines to induce heterologous protection against influenza in poultry. PMID:23200938

  12. Influenza

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The term "influenza" originally referred to epidemics of acute, rapidly spreading catarrhal fevers of humans caused by viruses in the family Orthomyxoviridae. Today, orthomyxoviruses are recognized as the cause of significant numbers of natural infections and disease, usually of the upper respirato...

  13. Effect of homosubtypic and heterosubtypic low pathogenic avian influenza exposure on H5N1 highly pathogenic avian influenza virus infection in wood ducks (Aix sponsa)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Wild birds in the Orders Anseriformes and Charadriiformes are the natural reservoirs for avian influenza (AI) viruses. Although they are often infected with multiple AI viruses, the significance and extent of acquired immunity in these populations is not understood. Pre-existing immunity to AI virus...

  14. Expression of H5 hemagglutinin vaccine antigen in common duckweed (Lemna minor) protects against H5N1 high pathogenicity avian influenza virus challenge in immunized chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A synthetic hemagglutinin (HA) gene from the highly pathogenic avian influenza (HPAI) virus A/chicken/Indonesia/7/2003 (H5N1) (Indo/03) was expressed in aquatic plant Lemna minor (rLemna-HA). In Experiment 1, efficacy of rLemna-HA was tested on specific pathogen free (SPF) birds immunized with 0.2 ...

  15. Biologic characterization of H4, H6, and H9 type low pathogenicity avian influenza viruses from wild birds in chickens and turkeys

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study, the pathogenesis, virus shedding and serologic response in specific pathogen-free chickens and commercial turkeys against H4, H6, and H9 type low pathogenic avian influenza viruses (LPAI) from wild birds was examined. Four week old chickens and three week old turkeys were given 1 x 10...

  16. 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...

  17. Host Regulatory Network Response to Infection with Highly Pathogenic H5N1 Avian Influenza Virus ▿ †

    PubMed Central

    Li, Chengjun; Bankhead, Armand; Eisfeld, Amie J.; Hatta, Yasuko; Jeng, Sophia; Chang, Jean H.; Aicher, Lauri D.; Proll, Sean; Ellis, Amy L.; Law, G. Lynn; Waters, Katrina M.; Neumann, Gabriele; Katze, Michael G.; McWeeney, Shannon; Kawaoka, Yoshihiro

    2011-01-01

    During the last decade, more than half of humans infected with highly pathogenic avian influenza (HPAI) H5N1 viruses have died, yet virus-induced host signaling has yet to be clearly elucidated. Airway epithelia are known to produce inflammatory mediators that contribute to HPAI H5N1-mediated pathogenicity, but a comprehensive analysis of the host response in this cell type is lacking. Here, we leveraged a system approach to identify and statistically validate signaling subnetworks that define the dynamic transcriptional response of human bronchial epithelial cells after infection with influenza A/Vietnam/1203/2004 (H5N1, VN1203). Importantly, we validated a subset of transcripts from one subnetwork in both Calu-3 cells and mice. A more detailed examination of two subnetworks involved in the immune response and keratinization processes revealed potential novel mediators of HPAI H5N1 pathogenesis and host response signaling. Finally, we show how these results compare to those for a less virulent strain of influenza virus. Using emergent network properties, we provide fresh insight into the host response to HPAI H5N1 virus infection and identify novel avenues for perturbation studies and potential therapeutic interventions for fatal HPAI H5N1 disease. PMID:21865398

  18. Protection of chickens against H5N1 highly pathogenic avian influenza virus infection by live vaccination with infectious laryngotracheitis virus recombinants expressing H5 hemagglutinin and N1 neuraminidase.

    PubMed

    Pavlova, Sophia P; Veits, Jutta; Keil, Günther M; Mettenleiter, Thomas C; Fuchs, Walter

    2009-01-29

    Attenuated vaccine strains of the alphaherpesvirus causing infectious laryngotracheitis of chickens (ILTV, gallid herpesvirus 1) can be used for mass application. Previously, we showed that live virus vaccination with recombinant ILTV expressing hemagglutinin of highly pathogenic avian influenza viruses (HPAIV) protected chickens against ILT and fowl plague caused by HPAIV carrying the corresponding hemagglutinin subtypes [Lüschow D, Werner O, Mettenleiter TC, Fuchs W. Protection of chickens from lethal avian influenza A virus infection by live-virus vaccination with infectious laryngotracheitis virus recombinants expressing the hemagglutinin (H5) gene. Vaccine 2001;19(30):4249-59; Veits J, Lüschow D, Kindermann K, Werner O, Teifke JP, Mettenleiter TC, et al. Deletion of the non-essential UL0 gene of infectious laryngotracheitis (ILT) virus leads to attenuation in chickens, and UL0 mutants expressing influenza virus haemagglutinin (H7) protect against ILT and fowl plague. J Gen Virol 2003;84(12):3343-52]. However, protection against H5N1 HPAIV was not satisfactory. Therefore, a newly designed dUTPase-negative ILTV vector was used for rapid insertion of the H5-hemagglutinin, or N1-neuraminidase genes of a recent H5N1 HPAIV isolate. Compared to our previous constructs, protein expression was considerably enhanced by insertion of synthetic introns downstream of the human cytomegalovirus immediate-early promoter within the 5'-nontranslated region of the transgenes. Deletion of the viral dUTPase gene did not affect in vitro replication of the ILTV recombinants, but led to sufficient attenuation in vivo. After a single ocular immunization, all chickens developed H5- or N1-specific serum antibodies. Nevertheless, animals immunized with N1-ILTV died after subsequent H5N1 HPAIV challenge, although survival times were prolonged compared to non-vaccinated controls. In contrast, all chickens vaccinated with either H5-ILTV alone, or H5- and N1-ILTV simultaneously, survived

  19. Antiviral activity of crude extracts of Eugenia jambolana Lam. against highly pathogenic avian influenza (H5N1) virus.

    PubMed

    Sood, Richa; Swarup, D; Bhatia, S; Kulkarni, D D; Dey, S; Saini, M; Dubey, S C

    2012-03-01

    Crude extracts of leaves and bark of E. jambolana were tested for antiviral activity against highly pathogenic avian influenza virus (H5N1) by CPE reduction assay in three different layouts to elucidate virucidal, post-exposure and preexposure antiviral activity of the extracts. The cold and hot aqueous extracts of bark and hot aqueous extract of leaves of E. jambolana showed significant virucidal activity (100% inhibition) which was further confirmed in virus yield reduction assay (-98 to 99% reduction) and by egg based in ovo assay. The selective index (CC50/EC50) of hot aqueous extract (248) and cold aqueous extract (43.5) of bark of E. jambolana showed their antiviral potential against H5N1 virus. The significant virucidal activity of leaves and bark of E. jambolana merits further investigation as it may provide alternative antiviral agent for managing avian influenza infections in poultry farms and potential avian-human transmission. PMID:22439432

  20. Reassessing the role of the NLRP3 inflammasome during pathogenic influenza A virus infection via temporal inhibition.

    PubMed

    Tate, Michelle D; Ong, James D H; Dowling, Jennifer K; McAuley, Julie L; Robertson, Avril B; Latz, Eicke; Drummond, Grant R; Cooper, Matthew A; Hertzog, Paul J; Mansell, Ashley

    2016-01-01

    The inflammasome NLRP3 is activated by pathogen associated molecular patterns (PAMPs) during infection, including RNA and proteins from influenza A virus (IAV). However, chronic activation by danger associated molecular patterns (DAMPs) can be deleterious to the host. We show that blocking NLRP3 activation can be either protective or detrimental at different stages of lethal influenza A virus (IAV). Administration of the specific NLRP3 inhibitor MCC950 to mice from one day following IAV challenge resulted in hypersusceptibility to lethality. In contrast, delaying treatment with MCC950 until the height of disease (a more likely clinical scenario) significantly protected mice from severe and highly virulent IAV-induced disease. These findings identify for the first time that NLRP3 plays a detrimental role later in infection, contributing to IAV pathogenesis through increased cytokine production and lung cellular infiltrates. These studies also provide the first evidence identifying NLRP3 inhibition as a novel therapeutic target to reduce IAV disease severity. PMID:27283237

  1. Reassessing the role of the NLRP3 inflammasome during pathogenic influenza A virus infection via temporal inhibition

    PubMed Central

    Tate, Michelle D.; Ong, James D. H.; Dowling, Jennifer K.; McAuley, Julie L.; Robertson, Avril B.; Latz, Eicke; Drummond, Grant R.; Cooper, Matthew A.; Hertzog, Paul J.; Mansell, Ashley

    2016-01-01

    The inflammasome NLRP3 is activated by pathogen associated molecular patterns (PAMPs) during infection, including RNA and proteins from influenza A virus (IAV). However, chronic activation by danger associated molecular patterns (DAMPs) can be deleterious to the host. We show that blocking NLRP3 activation can be either protective or detrimental at different stages of lethal influenza A virus (IAV). Administration of the specific NLRP3 inhibitor MCC950 to mice from one day following IAV challenge resulted in hypersusceptibility to lethality. In contrast, delaying treatment with MCC950 until the height of disease (a more likely clinical scenario) significantly protected mice from severe and highly virulent IAV-induced disease. These findings identify for the first time that NLRP3 plays a detrimental role later in infection, contributing to IAV pathogenesis through increased cytokine production and lung cellular infiltrates. These studies also provide the first evidence identifying NLRP3 inhibition as a novel therapeutic target to reduce IAV disease severity. PMID:27283237

  2. Pathobiology of Asian highly pathogenic avian influenza H5N1 virus infection in ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ducks and other wild aquatic birds are the natural reservoir of influenza type A viruses which normally are nonpathogenic in these birds. However, the Asian H5N1 avian influenza (AI) viruses have evolved from producing no disease or mild respiratory infections in ducks, to some strains producing se...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In order to develop better control measures against avian influenza (AI) it’s necessary to understand how the virus transmits in poultry. In a previous study in which the infectivity and transmissibility of the pandemic H1N1influenza virus was examined in different poultry species, we found that no ...

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

    PubMed

    Arafa, A; Suarez, D; Kholosy, S G; Hassan, M K; Nasef, S; Selim, A; Dauphin, G; Kim, M; Yilma, J; Swayne, D; Aly, M M

    2012-10-01

    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 as a part of the control strategy to help to control the disease. Epidemiological data with sequence analysis of H5N1 viruses is important to link the mechanism of virus evolution in Egypt. This study describes the evolutionary pattern of Egyptian H5N1 viruses based on molecular characterization for the isolates collected from commercial poultry farms and village poultry from 2006 to 2011. Genetic analysis of the hemagglutinin (HA) gene was done by sequencing of the full-length H5 gene. The epidemiological pattern of disease outbreaks in Egyptian poultry farms seems to be seasonal with no specific geographic distribution across the country. The molecular epidemiological data revealed that there are two major groups of viruses: the classic group of subclade 2.2.1 and a variant group of 2.2.1.1. The classic group is prevailing mainly in village poultry and had fewer mutations compared to the originally introduced virus in 2006. Since 2009, this group has started to be transmitted back to commercial sectors. The variant group emerged by late 2007, was prevalent mainly in vaccinated commercial poultry, mutated continuously at a higher rate until 2010, and started to decline in 2011. Genetic analysis of the neuraminidase (NA) gene and the other six internal genes indicates a grouping of the Egyptian viruses similar to that obtained using the HA gene, with no obvious reassortments. The results of this study indicate that HPAI-H5N1 viruses are progressively evolving and adapting in Egypt and continue to acquire new mutations every season. PMID:22760662

  5. Continuing Reassortant of H5N6 Subtype Highly Pathogenic Avian Influenza Virus in Guangdong.

    PubMed

    Yuan, Runyu; Wang, Zheng; Kang, Yinfeng; Wu, Jie; Zou, Lirong; Liang, Lijun; Song, Yingchao; Zhang, Xin; Ni, Hanzhong; Lin, Jinyan; Ke, Changwen

    2016-01-01

    First identified in May 2014 in China's Sichuan Province, initial cases of H5N6 avian influenza virus (AIV) infection in humans raised great concerns about the virus's prevalence, origin, and development. To evaluate both AIV contamination in live poultry markets (LPMs) and the risk of AIV infection in humans, we have conducted surveillance of LPMs in Guangdong Province since 2013 as part of environmental sampling programs. With environmental samples associated with these LPMs, we performed genetic and phylogenetic analyses of 10 H5N6 AIVs isolated from different cities of Guangdong Province from different years. Results revealed that the H5N6 viruses were reassortants with hemagglutinin (HA) genes derived from clade 2.3.4.4 of H5-subtype AIV, yet neuraminidase (NA) genes derived from H6N6 AIV. Unlike the other seven H5N6 viruses isolated in first 7 months of 2014, all of which shared remarkable sequence similarity with the H5N1 AIV in all internal genes, the PB2 genes of GZ693, GZ670, and ZS558 more closely related to H6N6 AIV and the PB1 gene of GZ693 to the H3-subtype AIV. Phylogenetic analyses revealed that the environmental H5N6 AIV related closely to human H5N6 AIVs isolated in Guangdong. These results thus suggest that continued reassortment has enabled the emergence of a novel H5N6 virus in Guangdong, as well as highlight the potential risk of highly pathogenic H5N6 AIVs in the province. PMID:27148209

  6. Evolution of highly pathogenic avian H5N1 influenza viruses

    SciTech Connect

    Macken, Catherine A; Green, Margaret A

    2009-01-01

    Highly pathogenic avian H5N1 viruses have circulated in Southeast Asia for more than a decade, are now endemic in parts of this region, and have also spread to more than 60 countries on three continents. The evolution of these viruses is characterized by frequent reassortment events that have created a significant number of different genotypes, both transient and longer lasting. However, fundamental questions remain about the generation and perpetuation of this substantial genetic diversity. These gaps in understanding may, in part, be due to the difficulties of genotyping closely related viruses, and limitations in the size of the data sets used in analysis. Using our recently published novel genotyping procedure ('two-time test'), which is amenable to high throughput analysis and provides an increased level of resolution relative to previous analyses, we propose a detailed model for the evolution and diversification of avian H5N1 viruses. Our analysis suggests that (i) all current H5N1 genotypes are derived from a single, clearly defined sequence of initial reassortment events; (ii) reassortment of the polymerase and NP genes may have played an important role in avian H5N1 virus evolution; (iii) the current genotype Z viruses have diverged into three distinguishable sub-genotypes in the absence of reassortment; (iv) some potentially significant molecular changes appear to be correlated with particular genotypes (for example, reassortment of the internal genes is often paralleled by a change in the HA clade); and (v) as noted in earlier studies of avian influenza A virus evolution, novel segments are typically derived from different donors (i.e., there is no obvious pattern of gene linkage in reassortment). The model of avian H5N1 viral evolution by reassortment and mutation that emerges from our study provides a context within which significant amino acid changes may be revealed; it also may help in predicting the 'success' of newly emerging avian H5N1 viruses.

  7. Continuing Reassortant of H5N6 Subtype Highly Pathogenic Avian Influenza Virus in Guangdong

    PubMed Central

    Yuan, Runyu; Wang, Zheng; Kang, Yinfeng; Wu, Jie; Zou, Lirong; Liang, Lijun; Song, Yingchao; Zhang, Xin; Ni, Hanzhong; Lin, Jinyan; Ke, Changwen

    2016-01-01

    First identified in May 2014 in China's Sichuan Province, initial cases of H5N6 avian influenza virus (AIV) infection in humans raised great concerns about the virus's prevalence, origin, and development. To evaluate both AIV contamination in live poultry markets (LPMs) and the risk of AIV infection in humans, we have conducted surveillance of LPMs in Guangdong Province since 2013 as part of environmental sampling programs. With environmental samples associated with these LPMs, we performed genetic and phylogenetic analyses of 10 H5N6 AIVs isolated from different cities of Guangdong Province from different years. Results revealed that the H5N6 viruses were reassortants with hemagglutinin (HA) genes derived from clade 2.3.4.4 of H5-subtype AIV, yet neuraminidase (NA) genes derived from H6N6 AIV. Unlike the other seven H5N6 viruses isolated in first 7 months of 2014, all of which shared remarkable sequence similarity with the H5N1 AIV in all internal genes, the PB2 genes of GZ693, GZ670, and ZS558 more closely related to H6N6 AIV and the PB1 gene of GZ693 to the H3-subtype AIV. Phylogenetic analyses revealed that the environmental H5N6 AIV related closely to human H5N6 AIVs isolated in Guangdong. These results thus suggest that continued reassortment has enabled the emergence of a novel H5N6 virus in Guangdong, as well as highlight the potential risk of highly pathogenic H5N6 AIVs in the province. PMID:27148209

  8. Highly Pathogenic Avian Influenza H5N1 in Mainland China

    PubMed Central

    Li, Xin-Lou; Liu, Kun; Yao, Hong-Wu; Sun, Ye; Chen, Wan-Jun; Sun, Ruo-Xi; de Vlas, Sake J.; Fang, Li-Qun; Cao, Wu-Chun

    2015-01-01

    Highly pathogenic avian influenza (HPAI) H5N1 has posed a significant threat to both humans and birds, and it has spanned large geographic areas and various ecological systems throughout Asia, Europe and Africa, but especially in mainland China. Great efforts in control and prevention of the disease, including universal vaccination campaigns in poultry and active serological and virological surveillance, have been undertaken in mainland China since the beginning of 2006. In this study, we aim to characterize the spatial and temporal patterns of HPAI H5N1, and identify influencing factors favoring the occurrence of HPAI H5N1 outbreaks in poultry in mainland China. Our study shows that HPAI H5N1 outbreaks took place sporadically after vaccination campaigns in poultry, and mostly occurred in the cold season. The positive tests in routine virological surveillance of HPAI H5N1 virus in chicken, duck, goose as well as environmental samples were mapped to display the potential risk distribution of the virus. Southern China had a higher positive rate than northern China, and positive samples were mostly detected from chickens in the north, while the majority were from duck in the south, and a negative correlation with monthly vaccination rates in domestic poultry was found (R = −0.19, p value = 0.005). Multivariate panel logistic regression identified vaccination rate, interaction between distance to the nearest city and national highway, interaction between distance to the nearest lake and wetland, and density of human population, as well as the autoregressive term in space and time as independent risk factors in the occurrence of HPAI H5N1 outbreaks, based on which a predicted risk map of the disease was derived. Our findings could provide new understanding of the distribution and transmission of HPAI H5N1 in mainland China and could be used to inform targeted surveillance and control efforts in both human and poultry populations to reduce the risk of future infections

  9. Is the optimal pH for membrane fusion in host cells by avian influenza viruses related to host range and pathogenicity?

    PubMed

    Okamatsu, Masatoshi; Motohashi, Yurie; Hiono, Takahiro; Tamura, Tomokazu; Nagaya, Kazuki; Matsuno, Keita; Sakoda, Yoshihiro; Kida, Hiroshi

    2016-08-01

    Influenza viruses isolated from wild ducks do not replicate in chickens. This fact is not explained solely by the receptor specificity of the hemagglutinin (HA) from such viruses for target host cells. To investigate this restriction in host range, the fusion activities of HA molecules from duck and chicken influenza viruses were examined. Influenza viruses A/duck/Mongolia/54/2001 (H5N2) (Dk/MNG) and A/chicken/Ibaraki/1/2005 (H5N2) (Ck/IBR), which replicate only in their primary hosts, were used. The optimal pH for membrane fusion of Ck/IBR was 5.9, higher than that of Dk/MNG at 4.9. To assess the relationship between the optimal pH for fusion and the host range of avian influenza viruses, the optimal pH for fusion of 55 influenza virus strains isolated from ducks and chickens was examined. No correlation was found between the host range and optimal pH for membrane fusion by the viruses, and this finding applied also to the H5N1 highly pathogenic avian influenza viruses. The optimal pH for membrane fusion for avian influenza viruses was shown to not necessarily be correlated with their host range or pathogenicity in ducks and chickens. PMID:27231009

  10. Low pathogenic avian influenza (H9N2) in chicken: Evaluation of an ancestral H9-MVA vaccine.

    PubMed

    Ducatez, Mariette F; Becker, Jens; Freudenstein, Astrid; Delverdier, Maxence; Delpont, Mattias; Sutter, Gerd; Guérin, Jean-Luc; Volz, Asisa

    2016-06-30

    Modified Vaccinia Ankara (MVA) has proven its efficacy as a recombinant vector vaccine for numerous pathogens including influenza virus. The present study aimed at evaluating a recombinant MVA candidate vaccine against low pathogenic avian influenza virus subtype H9N2 in the chicken model. As the high genetic and antigenic diversity of H9N2 viruses increases vaccine design complexity, one strategy to widen the range of vaccine coverage is to use an ancestor sequence. We therefore generated a recombinant MVA encoding for the gene sequence of an ancestral hemagglutinin H9 protein (a computationally derived amino acid sequence of the node of the H9N2 G1 lineage strains was obtained using the ANCESCON program). We analyzed the genetics and the growth properties of the MVA vector virus confirming suitability for use under biosafety level 1 and tested its efficacy when applied either as an intra-muscular (IM) or an oral vaccine in specific pathogen free chickens challenged with A/chicken/Tunisia/12/2010(H9N2). Two control groups were studied in parallel (unvaccinated and inoculated birds; unvaccinated and non-inoculated birds). IM vaccinated birds seroconverted as early as four days post vaccination and neutralizing antibodies were detected against A/chicken/Tunisia/12/2010(H9N2) in all the birds before challenge. The role of local mucosal immunity is unclear here as no antibodies were detected in eye drop or aerosol vaccinated birds. Clinical signs were not detected in any of the infected birds even in absence of vaccination. Virus replication was observed in both vaccinated and unvaccinated chickens, suggesting the MVA-ancestral H9 vaccine may not stop virus spread in the field. However vaccinated birds showed less histological damage, fewer influenza-positive cells and shorter virus shedding than their unvaccinated counterparts. PMID:27259828

  11. An outbreak of low pathogenic avian influenza in a mixed-species aviculture unit in Dubai in 2005.

    PubMed

    Kent, Jo; Bailey, Tom; Silvanose, Christu-Das; McKeown, Sean; Wernery, Ulrich; Kinne, Joerg; Manvell, Ruth

    2006-09-01

    This case describes an outbreak of low pathogenic hemagglutinin 9 neuraminidase 2 avian influenza virus (AIV) in two white-bellied bustards (Eupodotis senegalensis), one stone curlew (Burhinus oedicnemius), and a blacksmith plover (Antibyx armatus) in a private zoologic collection in Dubai, United Arab Emirates. The four birds showed signs of respiratory disease, and all died as a result of disease or euthanasia. Attention has been paid to the diagnostic process and common differential diagnosis for upper respiratory tract disease in bustards, curlews, and plovers. To the knowledge of the authors, AIV has not been previously described in these species. PMID:16931369

  12. Pathogenesis and transmission of H7 and H5 highly pathogenic avian influenza viruses in mallards including the recent intercontinental H5 viruses (H5N8 and H5N2)

    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 Asian lineage H5N1, and recently H5N8, HPAIVs, which can cause moderate to sev...

  13. Mucosal administration of raccoonpox virus expressing highly pathogenic avian H5N1 influenza neuraminidase is highly protective against H5N1 and seasonal influenza virus challenge.

    PubMed

    Kingstad-Bakke, Brock; Kamlangdee, Attapon; Osorio, Jorge E

    2015-09-22

    We previously generated recombinant poxviruses expressing influenza antigens and studied their efficacy as potential highly pathogenic avian influenza (HPAI) vaccines in mice. While both modified vaccinia Ankara (MVA) and raccoon poxvirus (RCN) expressing hemagglutinin (HA) provided strong protection when administered by parenteral routes, only RCN-neuraminidase (NA) showed promise as a mucosal vaccine. In the present study we evaluated the efficacy of RCN-NA constructs by both intradermal (ID) and intranasal (IN) routes. Surprisingly, while RCN-NA completely protected mice when administered by the IN route, it failed to protect mice when administered by the ID route. After challenge, significantly less virus induced pathology was observed in the lungs of mice vaccinated with RCN-NA by the IN route as compared to the ID route. Furthermore, IN administration of RCN-NA elicited neutralizing antibodies detected in bronchoalveolar lavage (BAL) samples. We also determined the role of cellular immune responses in protection elicited by RCN-NA by depleting CD4 and CD8 T cells prior to challenge. Finally, we demonstrated for the first time that antibodies against NA can block viral entry in addition to viral spread in vitro. These studies demonstrate the importance of mucosal administration of RCN viral vectors for eliciting protective immune responses against the NA antigen. PMID:26271828

  14. Pathogenicity of H5N8 highly pathogenic avian influenza viruses isolated from a wild bird fecal specimen and a chicken in Japan in 2014.

    PubMed

    Tanikawa, Taichiro; Kanehira, Katsushi; Tsunekuni, Ryota; Uchida, Yuko; Takemae, Nobuhiro; Saito, Takehiko

    2016-04-01

    Poultry outbreaks caused by H5N8 highly pathogenic avian influenza viruses (HPAIVs) occurred in Japan between December 2014 and January 2015. During the same period; H5N8 HPAIVs were isolated from wild birds and the environment in Japan. The hemagglutinin (HA) genes of these isolates were found to belong to clade 2.3.4.4 and three sub-groups were distinguishable within this clade. All of the Japanese isolates from poultry outbreaks belonged to the same sub-group; whereas wild bird isolates belonged to the other sub-groups. To examine whether the difference in pathogenicity to chickens between isolates of different HA sub-groups of clade 2.3.4.4 could explain why the Japanese poultry outbreaks were only caused by a particular sub-group; pathogenicities of A/chicken/Miyazaki/7/2014 (Miyazaki2014; sub-group C) and A/duck/Chiba/26-372-48/2014 (Chiba2014; sub-group A) to chickens were compared and it was found that the lethality of Miyazaki2014 in chickens was lower than that of Chiba2014; according to the 50% chicken lethal dose. This indicated that differences in pathogenicity may not explain why the Japanese poultry outbreaks only involved group C isolates. PMID:26916882

  15. Highly Pathogenic Avian Influenza Virus Subtype H5N1 Escaping Neutralization: More than HA Variation

    PubMed Central

    Höper, Dirk; Kalthoff, Donata; Hoffmann, Bernd

    2012-01-01

    Influenza A viruses are one of the major threats in modern health care. Novel viruses arise due to antigenic drift and antigenic shift, leading to escape from the immune system and resulting in a serious problem for disease control. In order to investigate the escape process and to enable predictions of escape, we serially passaged influenza A H5N1 virus in vitro 100 times under immune pressure. The generated escape viruses were characterized phenotypically and in detail by full-genome deep sequencing. Mutations already found in natural isolates were detected, evidencing the in vivo relevance of the in vitro-induced amino acid substitutions. Additionally, several novel alterations were triggered. Altogether, the results imply that our in vitro system is suitable to study influenza A virus evolution and that it might even be possible to predict antigenic changes of influenza A viruses circulating in vaccinated populations. PMID:22090121

  16. Contact between bird species of different lifespans can promote the emergence of highly pathogenic avian influenza strains

    PubMed Central

    Wikramaratna, Paul S.; Pybus, Oliver G.; Gupta, Sunetra

    2014-01-01

    Outbreaks of highly pathogenic strains of avian influenza viruses (AIVs) cause considerable economic losses to the poultry industry and also pose a threat to human life. The possibility that one of these strains will evolve to become transmissible between humans, sparking a major influenza pandemic, is a matter of great concern. Most studies so far have focused on assessing these odds from the perspective of the intrinsic mutability of AIV rather than the ecological constraints to invasion faced by the virus population. Here we present an alternative multihost model for the evolution of AIV in which the mode and tempo of mutation play a limited role, with the emergence of strains being determined instead principally by the prevailing profile of population-level immunity. We show that (i) many of the observed differences in influenza virus dynamics among species can be captured by our model by simply varying host lifespan and (ii) increased contact between species of different lifespans can promote the emergence of potentially more virulent strains that were hitherto suppressed in one of the species. PMID:24958867

  17. Description of an outbreak of highly pathogenic avian influenza in domestic ostriches (Struthio camelus) in South Africa in 2011.

    PubMed

    van Helden, L S; Sinclair, M; Koen, P; Grewar, J D

    2016-06-01

    In 2011, the commercial ostrich production industry of South Africa experienced an outbreak of highly pathogenic avian influenza (HPAI), subtype H5N2. Surveillance using antibody and antigen detection revealed 42 infected farms with a between-farm prevalence in the affected area of 16%. The outbreak was controlled using depopulation of infected farms, resulting in the direct loss of 10% of the country's domestic ostrich population. Various factors in the ostrich production system were observed that could have contributed to the spread of the virus between farms, including the large number of legal movements of ostriches between farms, access of wild birds to ostrich camps and delays in depopulation of infected farms. Negative effects on the ostrich industry and the local economy of the ostrich-producing area were observed as a result of the outbreak and the disease control measures applied. Prevention and control measures applied as a result of avian influenza in South Africa were informed by this large outbreak and the insights into epidemiology of avian influenza in ostriches that it provided, resulting in stricter biosecurity measures required on every registered ostrich farm in the country. PMID:27237385

  18. Pathobiological characterization of low-pathogenicity H5 avian influenza viruses of diverse origins in chickens, ducks and turkeys.

    PubMed

    Pillai, S P S; Pantin-Jackwood, M; Suarez, D L; Saif, Y M; Lee, C-W

    2010-09-01

    We undertook one of the most comprehensive studies on the replication and intraspecies transmission characteristics of low-pathogenicity avian influenza viruses in ducks, chickens and turkeys. Our results indicated that most of these isolates could replicate and be transmitted in poultry without inducing clinical disease. However, differences in transmission to contact control birds were noted, emphasizing the importance of having contact control cage mates in biological characterization experiments. Ducks supported the replication of viruses of wild aquatic bird origin in their respiratory and digestive tracts equally well. The viruses from wild aquatic birds were not effectively transmitted among chickens. In contrast, the wild-bird isolates and viruses of domestic bird origin from live-bird markets and commercial poultry operations replicated and were transmitted more efficiently in turkeys than in chickens or ducks. We also found a lower minimal infectious dose requirement for infection of turkeys compared to chickens and ducks. Our data support an important role of turkeys as being more susceptible hosts for avian influenza viruses than domestic ducks and chickens. These results highlight the role of turkeys as intermediate or bridging hosts in the transmission of influenza viruses from wild birds to land-based domestic poultry or among different land-based bird species. PMID:20577770

  19. Avian influenza virus hemagglutinins H2, H4, H8, and H14 support a highly pathogenic phenotype

    PubMed Central

    Veits, Jutta; Weber, Siegfried; Stech, Olga; Breithaupt, Angele; Gräber, Marcus; Gohrbandt, Sandra; Bogs, Jessica; Hundt, Jana; Teifke, Jens P.; Mettenleiter, Thomas C.; Stech, Jürgen

    2012-01-01

    High-pathogenic avian influenza viruses (HPAIVs) evolve from low-pathogenic precursors specifying the HA serotypes H5 or H7 by acquisition of a polybasic HA cleavage site. As the reason for this serotype restriction has remained unclear, we aimed to distinguish between compatibility of a polybasic cleavage site with H5/H7 HA only and unique predisposition of these two serotypes for insertion mutations. To this end, we introduced a polybasic cleavage site into the HA of several low-pathogenic avian strains with serotypes H1, H2, H3, H4, H6, H8, H10, H11, H14, or H15, and rescued HA reassortants after cotransfection with the genes from either a low-pathogenic H9N2 or high-pathogenic H5N1 strain. Oculonasal inoculation with those reassortants resulted in varying pathogenicity in chicken. Recombinants containing the engineered H2, H4, H8, or H14 in the HPAIV background were lethal and exhibited i.v. pathogenicity indices of 2.79, 2.37, 2.85, and 2.61, respectively, equivalent to naturally occurring H5 or H7 HPAIV. Moreover, the H2, H4, and H8 reassortants were transmitted to some contact chickens. The H2 reassortant gained two mutations in the M2 proton channel gate region, which is affected in some HPAIVs of various origins. Taken together, in the presence of a polybasic HA cleavage site, non-H5/H7 HA can support a highly pathogenic phenotype in the appropriate viral background, indicating requirement for further adaptation. Therefore, the restriction of natural HPAIV to serotypes H5 and H7 is likely a result of their unique predisposition for acquisition of a polybasic HA cleavage site. PMID:22308331

  20. Experimental infection of SPF and Korean native chickens with highly pathogenic avian influenza virus (H5N8).

    PubMed

    Lee, Eun-Kyoung; Song, Byung-Min; Kang, Hyun-Mi; Woo, Sang-Hee; Heo, Gyeong-Beom; Jung, Suk Chan; Park, Yong Ho; Lee, Youn-Jeong; Kim, Jae-Hong

    2016-05-01

    In 2014, an H5N8 outbreak of highly pathogenic avian influenza (HPAI) occurred in South Korea. The H5N8 strain produced mild to moderate clinical signs and mortality rates in commercial chicken farms, especially Korean native chicken farms. To understand the differences between their pathogenicity in SPF chicken and Korean native chicken., we evaluated the mean bird lethal doses (BLD50) of the Korean representative H5N8 virus (A/broiler duck/Korea/Buan2/2014) The BLD50values of the H5N8 virus were 10(5.3)EID50and 10(6.7)EID50in SPF and Korean native chickens, respectively. In addition, the mean death time was much longer, and the viral titers in tissues of H5N8-infected chickens were significantly lower, in the Korean group than in the SPF group. These features of the H5N8 virus likely account for its mild-to-moderate pathogenicity in commercial chicken farms, especially Korean native chicken flocks, despite the fact that it is a highly pathogenic virus according to the OIE criteria. To improve current understanding and management of HPAI, pathogenic characterization of novel emerging viruses should be performed by natural route in major poultry species in each country. PMID:26933235

  1. Low-pathogenicity avian influenza virus (H6N2) in chickens in California, 2000-02.

    PubMed

    Woolcock, P R; Suarez, D L; Kuney, D

    2003-01-01

    During 2000, 2001, and January 2002, avian influenza virus was isolated from chickens from 12 different locations in California. All the isolates were typed as H6N2 and determined to be of low pathogenicity for chickens. Nine of the isolates came from commercial layer flocks; one from a backyard flock; one from a mixed age flock, where ducks and squabs were also present; and one from a primary broiler breeder. Although a drop in egg production and increased mortality were among the disease signs reported in the layer flocks, the pathological changes observed in the early cases were primarily associated with mild respiratory infections. It was not until August 2001 that yolk peritonitis was observed; this has been a feature of all the remaining cases through 2001 and 2002. All the isolates clustered as a unique group separate from other influenza viruses based upon sequence data of the H6, neuraminidase (N2), and matrix (MA) genes, indicating a common ancestor for these three gene segments. However, sequencing of the nonstructural (NS) gene indicates introductions from two separate origins. With the first isolate CK/CA/431/00 as the index case, the N2, MA, and NS genes are more closely related to North American isolates, as is the NP gene of CK/CA/650/00. In contrast, the H6 gene is more closely related to a Eurasian influenza isolate. Comparison of amino acid sequences of the N2 and MA genes of these isolates with available type A influenza viruses identified two unique changes in the MA gene and nine in the N2 gene, as well as four progressive changes. These results are discussed in relation to available clinical and epidemiological data. PMID:14575080

  2. Human Sentinel Surveillance of Influenza and Other Respiratory Viral Pathogens in Border Areas of Western Cambodia

    PubMed Central

    Chuang, Ilin; Samon, Nou; Uthaimongkol, Nichapat; Klungthong, Chonticha; Manasatienkij, Wudtichai; Thaisomboonsuk, Butsaya; Tyner, Stuart D.; Rith, Sareth; Horm, Viseth Srey; Jarman, Richard G.; Bethell, Delia; Chanarat, Nitima; Pavlin, Julie; Wongstitwilairoong, Tippa; Saingam, Piyaporn; El, But Sam; Fukuda, Mark M.; Touch, Sok; Sovann, Ly; Fernandez, Stefan; Buchy, Philippe; Chanthap, Lon; Saunders, David

    2016-01-01

    Little is known about circulation of influenza and other respiratory viruses in remote populations along the Thai-Cambodia border in western Cambodia. We screened 586 outpatients (median age 5, range 1–77) presenting with influenza-like-illness (ILI) at 4 sentinel sites in western Cambodia between May 2010 and December 2012. Real-time reverse transcriptase (rRT) PCR for influenza was performed on combined nasal and throat specimens followed by viral culture, antigenic analysis, antiviral susceptibility testing and full genome sequencing for phylogenetic analysis. ILI-specimens negative for influenza were cultured, followed by rRT-PCR for enterovirus and rhinovirus (EV/RV) and EV71. Influenza was found in 168 cases (29%) and occurred almost exclusively in the rainy season from June to November. Isolated influenza strains had close antigenic and phylogenetic relationships, matching vaccine and circulating strains found elsewhere in Cambodia. Influenza vaccination coverage was low (<20%). Western Cambodian H1N1(2009) isolate genomes were more closely related to 10 earlier Cambodia isolates (94.4% genome conservation) than to 13 Thai isolates (75.9% genome conservation), despite sharing the majority of the amino acid changes with the Thai references. Most genes showed signatures of purifying selection. Viral culture detected only adenovirus (5.7%) and parainfluenza virus (3.8%), while non-polio enteroviruses (10.3%) were detected among 164 culture-negative samples including coxsackievirus A4, A6, A8, A9, A12, B3, B4 and echovirus E6 and E9 using nested RT-PCR methods. A single specimen of EV71 was found. Despite proximity to Thailand, influenza epidemiology of these western Cambodian isolates followed patterns observed elsewhere in Cambodia, continuing to support current vaccine and treatment recommendations from the Cambodian National Influenza Center. Amino acid mutations at non-epitope sites, particularly hemagglutinin genes, require further investigation in light

  3. Human Sentinel Surveillance of Influenza and Other Respiratory Viral Pathogens in Border Areas of Western Cambodia.

    PubMed

    Timmermans, Ans; Melendrez, Melanie C; Se, Youry; Chuang, Ilin; Samon, Nou; Uthaimongkol, Nichapat; Klungthong, Chonticha; Manasatienkij, Wudtichai; Thaisomboonsuk, Butsaya; Tyner, Stuart D; Rith, Sareth; Horm, Viseth Srey; Jarman, Richard G; Bethell, Delia; Chanarat, Nitima; Pavlin, Julie; Wongstitwilairoong, Tippa; Saingam, Piyaporn; El, But Sam; Fukuda, Mark M; Touch, Sok; Sovann, Ly; Fernandez, Stefan; Buchy, Philippe; Chanthap, Lon; Saunders, David

    2016-01-01

    Little is known about circulation of influenza and other respiratory viruses in remote populations along the Thai-Cambodia border in western Cambodia. We screened 586 outpatients (median age 5, range 1-77) presenting with influenza-like-illness (ILI) at 4 sentinel sites in western Cambodia between May 2010 and December 2012. Real-time reverse transcriptase (rRT) PCR for influenza was performed on combined nasal and throat specimens followed by viral culture, antigenic analysis, antiviral susceptibility testing and full genome sequencing for phylogenetic analysis. ILI-specimens negative for influenza were cultured, followed by rRT-PCR for enterovirus and rhinovirus (EV/RV) and EV71. Influenza was found in 168 cases (29%) and occurred almost exclusively in the rainy season from June to November. Isolated influenza strains had close antigenic and phylogenetic relationships, matching vaccine and circulating strains found elsewhere in Cambodia. Influenza vaccination coverage was low (<20%). Western Cambodian H1N1(2009) isolate genomes were more closely related to 10 earlier Cambodia isolates (94.4% genome conservation) than to 13 Thai isolates (75.9% genome conservation), despite sharing the majority of the amino acid changes with the Thai references. Most genes showed signatures of purifying selection. Viral culture detected only adenovirus (5.7%) and parainfluenza virus (3.8%), while non-polio enteroviruses (10.3%) were detected among 164 culture-negative samples including coxsackievirus A4, A6, A8, A9, A12, B3, B4 and echovirus E6 and E9 using nested RT-PCR methods. A single specimen of EV71 was found. Despite proximity to Thailand, influenza epidemiology of these western Cambodian isolates followed patterns observed elsewhere in Cambodia, continuing to support current vaccine and treatment recommendations from the Cambodian National Influenza Center. Amino acid mutations at non-epitope sites, particularly hemagglutinin genes, require further investigation in light

  4. Ecological Determinants of Highly Pathogenic Avian Influenza (H5N1) Outbreaks in Bangladesh

    PubMed Central

    Ahmed, Syed S. U.; Ersbøll, Annette K.; Biswas, Paritosh K.; Christensen, Jens P.; Hannan, Abu S. M. A.; Toft, Nils

    2012-01-01

    Background The agro-ecology and poultry husbandry of the south Asian and south-east Asian countries share common features, however, with noticeable differences. Hence, the ecological determinants associated with risk of highly pathogenic avian influenza (HPAI-H5N1) outbreaks are expected to differ between Bangladesh and e.g., Thailand and Vietnam. The primary aim of the current study was to establish ecological determinants associated with the risk of HPAI-H5N1 outbreaks at subdistrict level in Bangladesh. The secondary aim was to explore the performance of two different statistical modeling approaches for unmeasured spatially correlated variation. Methodology/Principal Findings An ecological study at subdistrict level in Bangladesh was performed with 138 subdistricts with HPAI-H5N1 outbreaks during 2007–2008, and 326 subdistricts with no outbreaks. The association between ecological determinants and HPAI-H5N1 outbreaks was examined using a generalized linear mixed model. Spatial clustering of the ecological data was modeled using 1) an intrinsic conditional autoregressive (ICAR) model at subdistrict level considering their first order neighbors, and 2) a multilevel (ML) model with subdistricts nested within districts. Ecological determinants significantly associated with risk of HPAI-H5N1 outbreaks at subdistrict level were migratory birds' staging areas, river network, household density, literacy rate, poultry density, live bird markets, and highway network. Predictive risk maps were derived based on the resulting models. The resulting models indicate that the ML model absorbed some of the covariate effect of the ICAR model because of the neighbor structure implied in the two different models. Conclusions/Significance The study identified a new set of ecological determinants related to river networks, migratory birds' staging areas and literacy rate in addition to already known risk factors, and clarified that the generalized concept of free grazing duck and

  5. Vaccination with Recombinant RNA Replicon Particles Protects Chickens from H5N1 Highly Pathogenic Avian Influenza Virus

    PubMed Central

    Halbherr, Stefan J.; Brostoff, Terza; Tippenhauer, Merve; Locher, Samira; Berger Rentsch, Marianne; Zimmer, Gert

    2013-01-01

    Highly pathogenic avian influenza viruses (HPAIV) of subtype H5N1 not only cause a devastating disease in domestic chickens and turkeys but also pose a continuous threat to public health. In some countries, H5N1 viruses continue to circulate and evolve into new clades and subclades. The rapid evolution of these viruses represents a problem for virus diagnosis and control. In this work, recombinant vesicular stomatitis virus (VSV) vectors expressing HA of subtype H5 were generated. To comply with biosafety issues the G gene was deleted from the VSV genome. The resulting vaccine vector VSV*ΔG(HA) was propagated on helper cells providing the VSV G protein in trans. Vaccination of chickens with a single intramuscular dose of 2×108 infectious replicon particles without adjuvant conferred complete protection from lethal H5N1 infection. Subsequent application of the same vaccine strongly boosted the humoral immune response and completely prevented shedding of challenge virus and transmission to sentinel birds. The vaccine allowed serological differentiation of infected from vaccinated animals (DIVA) by employing a commercially available ELISA. Immunized chickens produced antibodies with neutralizing activity against multiple H5 viruses representing clades 1, 2.2, 2.5, and low-pathogenic avian influenza viruses (classical clade). Studies using chimeric H1/H5 hemagglutinins showed that the neutralizing activity was predominantly directed against the globular head domain. In summary, these results suggest that VSV replicon particles are safe and potent DIVA vaccines that may help to control avian influenza viruses in domestic poultry. PMID:23762463

  6. Spatial Modeling of Wild Bird Risk Factors for Highly Pathogenic A(H5N1) Avian Influenza Virus Transmission.

    PubMed

    Prosser, Diann J; Hungerford, Laura L; Erwin, R Michael; Ottinger, Mary Ann; Takekawa, John Y; Newman, Scott H; Xiao, Xiangming; Ellis, Erle C

    2016-05-01

    One of the longest-persisting avian influenza viruses in history, highly pathogenic avian influenza virus (HPAIV) A(H5N1), continues to evolve after 18 yr, advancing the threat of a global pandemic. Wild waterfowl (family Anatidae) are reported as secondary transmitters of HPAIV and primary reservoirs for low-pathogenic avian influenza viruses, yet spatial inputs for disease risk modeling for this group have been lacking. Using geographic information software and Monte Carlo simulations, we developed geospatial indices of waterfowl abundance at 1 and 30 km resolutions and for the breeding and wintering seasons for China, the epicenter of H5N1. Two spatial layers were developed: cumulative waterfowl abundance (WAB), a measure of predicted abundance across species, and cumulative abundance weighted by H5N1 prevalence (WPR), whereby abundance for each species was adjusted based on prevalence values and then totaled across species. Spatial patterns of the model output differed between seasons, with higher WAB and WPR in the northern and western regions of China for the breeding season and in the southeast for the wintering season. Uncertainty measures indicated highest error in southeastern China for both WAB and WPR. We also explored the effect of resampling waterfowl layers from 1 to 30 km resolution for multiscale risk modeling. Results indicated low average difference (less than 0.16 and 0.01 standard deviations for WAB and WPR, respectively), with greatest differences in the north for the breeding season and southeast for the wintering season. This work provides the first geospatial models of waterfowl abundance available for China. The indices provide important inputs for modeling disease transmission risk at the interface of poultry and wild birds. These models are easily adaptable, have broad utility to both disease and conservation needs, and will be available to the scientific community for advanced modeling applications. PMID:27309075

  7. 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

  8. Practices associated with Highly Pathogenic Avian Influenza spread in traditional poultry marketing chains: Social and economic perspectives.

    PubMed

    Paul, Mathilde; Baritaux, Virginie; Wongnarkpet, Sirichai; Poolkhet, Chaithep; Thanapongtharm, Weerapong; Roger, François; Bonnet, Pascal; Ducrot, Christian

    2013-04-01

    In developing countries, smallholder poultry production contributes to food security and poverty alleviation in rural areas. However, traditional poultry marketing chains have been threatened by the epidemics caused by the Highly Pathogenic Avian Influenza (H5N1) virus. The article presents a value chain analysis conducted on the traditional poultry marketing chain in the rural province of Phitsanulok, Thailand. The analysis is based on quantitative data collected on 470 backyard chicken farms, and on qualitative data collected on 28 poultry collectors, slaughterhouses and market retailers, using semi-structured interviews. The article examines the organization of poultry marketing chains in time and space, and shows how this may contribute to the spread of Highly Pathogenic Avian Influenza H5N1 in the small-scale poultry sector. The article also discusses the practices and strategies developed by value chain actors facing poultry mortality, with their economic and social determinants. More broadly, this study also illustrates how value chain analysis can contribute to a better understanding of the complex mechanisms associated with the spread of epidemics in rural communities. PMID:23337390

  9. 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.

  10. Highly Pathogenic Avian Influenza A(H5N1) Virus Struck Migratory Birds in China in 2015

    PubMed Central

    Bi, Yuhai; Zhang, Zhenjie; Liu, Wenjun; Yin, Yanbo; Hong, Jianmin; Li, Xiangdong; Wang, Haiming; Wong, Gary; Chen, Jianjun; Li, Yunfeng; Ru, Wendong; Gao, Ruyi; Liu, Di; Liu, Yingxia; Zhou, Boping; Gao, George F.; Shi, Weifeng; Lei, Fumin

    2015-01-01

    Approximately 100 migratory birds, including whooper swans and pochards, were found dead in the Sanmenxia Reservoir Area of China during January 2015. The causative agent behind this outbreak was identified as H5N1 highly pathogenic avian influenza virus (HPAIV). Genetic and phylogenetic analyses revealed that this Sanmenxia H5N1 virus was a novel reassortant, possessing a Clade 2.3.2.1c HA gene and a H9N2-derived PB2 gene. Sanmenxia Clade 2.3.2.1c-like H5N1 viruses possess the closest genetic identity to A/Alberta/01/2014 (H5N1), which recently caused a fatal respiratory infection in Canada with signs of meningoencephalitis, a highly unusual symptom with influenza infections in humans. Furthermore, this virus was shown to be highly pathogenic to both birds and mammals, and demonstrate tropism for the nervous system. Due to the geographical location of Sanmenxia, these novel H5N1 viruses also have the potential to be imported to other regions through the migration of wild birds, similar to the H5N1 outbreak amongst migratory birds in Qinghai Lake during 2005. Therefore, further investigation and monitoring is required to prevent this novel reassortant virus from becoming a new threat to public health. PMID:26259704

  11. Phylogenetic and Pathogenic Analyses of Avian Influenza A H5N1 Viruses Isolated from Poultry in Vietnam

    PubMed Central

    Li, Yanbing; Jiang, Yongping; Liu, Liling; Chen, Hualan

    2012-01-01

    Despite great efforts to control the infection of poultry with H5N1 viruses, these pathogens continue to evolve and spread in nature, threatening public health. Elucidating the characteristics of H5N1 avian influenza virus will benefit disease control and pandemic preparation. Here, we sequenced the genomes of 15 H5N1 avian influenza viruses isolated in Vietnam in 2006 and 2007 and performed phylogenetic analyses to compare these sequences with those of other viruses available in the public databases. Molecular characterization of the H5N1 viruses revealed that seven genetically distinct clades of H5N1 viruses have appeared in Vietnam. Clade 2.3.4 viruses existed in Vietnam as early as 2005. Fifteen viruses isolated during 2006 and 2007 belonged to clade 1 and clade 2.3.4, and were divided into five genotypes. Reassortants between the clade 1 and clade 2.3.4 viruses were detected in both North and South Vietnam. We also assessed the replication and pathogenicity of these viruses in mice and found that these isolates replicated efficiently and exhibited distinct virulence in mice. Our results provide important information regarding the diversity of H5N1 viruses in nature. PMID:23226433

  12. Isolation and identification of highly pathogenic avian influenza virus subtype H5N1 in peafowl (Pavo cristatus).

    PubMed

    Ismail, Mahmoud Moussa; Khan, Owais Ahmed; Cattoli, Giovanni; Lu, Huaguang

    2010-03-01

    An outbreak of highly pathogenic avian influenza (HPAI) virus subtype H5N1 was first diagnosed in a "backyard" flock of peafowl (Pavo cristatus) raised on palace premises in the Kingdom of Saudi Arabia in December 3, 2007. The flock consisted of 40 peafowl, and their ages ranged from 3 to 5 years old. Affected birds suffered from depression, anorexia, and white diarrhea. Four dead birds were submitted for HPAI diagnosis at the Central Veterinary Diagnostic Laboratory in Riyadh. Brain and liver tissues and tracheal and cloacal swabs were taken from the dead birds and processed for a real-time reverse transcriptase (RT)-PCR test and virus isolation in specific-pathogen-free embryonating chicken eggs. The H5N1 subtype of avian influenza virus was isolated from the four dead birds and identified by a real-time RT-PCR before and after egg inoculation. The virus isolates were characterized as HPAI H5N1 virus by sequencing analysis. Phylogenetic comparisons revealed that the H5N1 viruses isolated from peafowl belong to the genetic clade 2.2 according to the World Health Organization nomenclature. The peafowl H5N1 virus falls into 2.2.2 sublineage II and clusters with the H5N1 viruses isolated from poultry in Saudi Arabia in 2007-08. PMID:20521659

  13. Protective efficacy of recombinant and inactivated H5 avian influenza vaccines against challenge from the 2014 intercontinental H5 highly pathogenic avian influenza viruses (H5N8 and H5N2)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Protective immunity against highly pathogenic avian influenza (HPAI) largely depends on the development of an antibody response against a specific subtype of challenge virus. Historically, the use of antigenically closely matched isolates has proven efficacious when used as inactivated vaccines. M...

  14. Pathogenicity of Genetically Similar, H5N1 Highly Pathogenic Avian Influenza Virus Strains in Chicken and the Differences in Sensitivity among Different Chicken Breeds

    PubMed Central

    Matsuu, Aya; Kobayashi, Tomoko; Patchimasiri, Tuangthong; Shiina, Takashi; Suzuki, Shingo; Chaichoune, Kridsada; Ratanakorn, Parntep; Hiromoto, Yasuaki; Abe, Haruka; Parchariyanon, Sujira; Saito, Takehiko

    2016-01-01

    Differences in the pathogenicity of genetically closely related H5N1 highly pathogenic avian influenza viruses (HPAIVs) were evaluated in White Leghorn chickens. These viruses varied in the clinical symptoms they induced, including lethality, virus shedding, and replication in host tissues. A comparison of the host responses in the lung, brain, and spleen suggested that the differences in viral replication efficiency were related to the host cytokine response at the early phase of infection, especially variations in the proinflammatory cytokine IL-6. Based on these findings, we inoculated the virus that showed the mildest pathogenicity among the five tested, A/pigeon/Thailand/VSMU-7-NPT/2004, into four breeds of Thai indigenous chicken, Phadu-Hung-Dang (PHD), Chee, Dang, and Luang-Hung-Khao (LHK), to explore effects of genetic background on host response. Among these breeds, Chee, Dang, and LHK showed significantly longer survival times than White Leghorns. Virus shedding from dead Thai indigenous chickens was significantly lower than that from White Leghorns. Although polymorphisms were observed in the Mx and MHC class I genes, there was no significant association between the polymorphisms in these loci and resistance to HPAIV. PMID:27078641

  15. Phylogenetic and pathogenic analysis of a novel H6N2 avian influenza virus isolated from a green peafowl in a wildlife park.

    PubMed

    Fan, Zhaobin; Ci, Yanpeng; Ma, Yixin; Liu, Liling; Ma, Jianzhang; Li, D Yanbing; Chen, Hualan

    2014-12-01

    H6 subtype avian influenza virus, which has been circulating among different species, causes considerable concern for both veterinary medicine and public health. We isolated a strain of H6N2 avian influenza virus from healthy green peafowl (Pavo muticus) in Qinghuangdao Wildlife Park in Hebei Province, China, in 2012. A phylogenetic analysis indicated that the isolated H6N2 strain had the same gene constellation as southern China strains, which were predominantly isolated from waterfowl distributed in Shantou, Guangxi, and Hunan in 2001-2010. The isolate showed no and low pathogenicity in chickens and ducks, respectively. However, it replicated efficiently in the lungs and turbinate of infected mice, resulting in thickened alveolar septa and moderate interstitial pneumonia. This finding raises concerns that the H6N2 subtype maybe evolve into a novel endemic avian influenza virus. Therefore, periodical surveillance of avian influenza viruses must be undertaken to monitor the advent of novel viruses. PMID:25619010

  16. Molecular pathogenesis of H5 highly pathogenic avian influenza: the role of the haemagglutinin cleavage site motif.

    PubMed

    Luczo, Jasmina M; Stambas, John; Durr, Peter A; Michalski, Wojtek P; Bingham, John

    2015-11-01

    The emergence of H5N1 highly pathogenic avian influenza has caused a heavy socio-economic burden through culling of poultry to minimise human and livestock infection. Although human infections with H5N1 have to date been limited, concerns for the pandemic potential of this zoonotic virus have been greatly intensified following experimental evidence of aerosol transmission of H5N1 viruses in a mammalian infection model. In this review, we discuss the dominance of the haemagglutinin cleavage site motif as a pathogenicity determinant, the host-pathogen molecular interactions driving cleavage activation, reverse genetics manipulations and identification of residues key to haemagglutinin cleavage site functionality and the mechanisms of cell and tissue damage during H5N1 infection. We specifically focus on the disease in chickens, as it is in this species that high pathogenicity frequently evolves and from which transmission to the human population occurs. With >75% of emerging infectious diseases being of zoonotic origin, it is necessary to understand pathogenesis in the primary host to explain spillover events into the human population. PMID:26467906

  17. Protective immunity against H7N3 highly pathogenic avian influenza induced following inoculation of chickens with H7 low pathogenic avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the poultry industry, live virus vaccines are used to induce immunity against numerous respiratory pathogens. These are typically lower virulent forms of virus which are limited in replication and pathology, but induce mucosal, humoral, and cellular immunity. Because of the potential for revers...

  18. Amantadine resistance among highly pathogenic avian influenza viruses (H5N1) isolated from India.

    PubMed

    Jacob, Aron; Sood, Richa; Chanu, Kh Victoria; Bhatia, Sandeep; Khandia, Rekha; Pateriya, A K; Nagarajan, S; Dimri, U; Kulkarni, D D

    2016-02-01

    Emergence of antiviral resistance among H5N1 avian influenza viruses is the major challenge in the control of pandemic influenza. Matrix 2 (M2) inhibitors (amantadine and rimantadine) and neuraminidase inhibitors (oseltamivir and zanamivir) are the two classes of antiviral agents that are specifically active against influenza viruses and are used for both treatment and prophylaxis of influenza infections. Amantadine targets the M2 ion channel of influenza A virus and interrupts virus life cycle through blockade of hydrogen ion influx. This prevents uncoating of the virus in infected host cells which impedes the release of ribonucleoprotein required for transcription and replication of virion in the nucleus. The present study was carried out to review the status of amantadine resistance in H5N1 viruses isolated from India and to study their replicative capability. Results of the study revealed resistance to amantadine in antiviral assay among four H5N1 viruses out of which two viruses had Serine 31 Asparagine (AGT-AAT i.e., S31N) mutation and two had Valine 27 Alanine (GTT-GCT i.e., V27A) mutation. The four resistant viruses not only exhibited significant difference in effective concentration 50% (EC50) values of amantadine hydrochloride from that of susceptible viruses (P < 0.0001) but also showed significant difference between two different types (S31N and V27A) of mutant viruses (P < 0.05). Resistance to amantadine could also be demonstrated in a simple HA test after replication of the viruses in MDCK cells in presence of amantadine. The study identifies the correlation between in vitro antiviral assay and presence of established molecular markers of resistance, the retention of replicative capacity in the presence of amantadine hydrochloride by the resistant viruses and the emergence of resistant mutations against amantadine among avian influenza viruses (H5N1) without selective drug pressure. PMID:26639679

  19. Cytomegalovirus appendicitis in an immunocompetent host.

    PubMed

    Canterino, Joseph E; McCormack, Michael; Gurung, Ananta; Passarelli, James; Landry, Marie L; Golden, Marjorie

    2016-05-01

    Cytomegalovirus (CMV) is a common viral pathogen. Asymptomatic infection or a mononucleosis syndrome are the most common manifestations in otherwise healthy individuals. End-organ disease is rare in immunocompetent individuals. Here, we describe a case of CMV appendicitis in a patient without an immune-compromising condition. PMID:26942831

  20. Multiplex polymerase chain reaction for the detection and differentiation of avian influenza viruses and other poultry respiratory pathogens.

    PubMed

    Rashid, S; Naeem, K; Ahmed, Z; Saddique, N; Abbas, M A; Malik, S A

    2009-12-01

    A multiplex reverse transcription-PCR (mRT-PCR) was developed and standardized for the detection of type A influenza viruses, avian influenza virus (AIV) subtype H7, H9, and H5 hemagglutinin gene with simultaneous detection of 3 other poultry respiratory pathogens, Newcastle disease virus (NDV), infectious bronchitis virus (IBV), and infectious laryngotracheitis virus (ILTV). Seven sets of specific oligonucleotide primers were used in this study for the M gene of AIV and hemagglutinin gene of subtypes H7, H9, and H5 of AIV. Three sets of other specific oligonucleotide primers were used for the detection of avian respiratory pathogens other than AIV. The mRT-PCR DNA products were visualized by agarose gel electrophoresis and consisted of DNA fragments of 1,023 bp for M gene of AIV, 149 bp for IBV, 320 bp for NDV, and 647 bp for ILTV. The second set of primers used for m-RT-PCR of H7N3, H9N2, and H5N1 provided DNA products of 300 bp for H7, 456 bp for H5, and 808 bp for H9. The mRT-PCR products for the third format consisted of DNA fragments of 149 bp for IBV, 320 bp for NDV, 647 bp for ILTV, 300 bp for H7, 456 bp for H5, and 808 bp for H9. The sensitivity and specificity of mRT-PCR was determined and the test was found to be sensitive and specific for the detection of AIV and other poultry respiratory pathogens. In this present study, multiplex PCR technique has been developed to simultaneously detect and differentiate the 3 most important subtypes of AIV along with the 3 most common avian respiratory pathogens prevalent in poultry in Pakistan. Therefore, a mRT-PCR that can rapidly differentiate between these pathogens will be very important for the control of disease transmission in poultry and in humans, along with the identification of 3 of the most common respiratory pathogens often seen as mixed infections in poultry, and hence economic losses will be reduced in poultry. PMID:19903950

  1. 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...

  2. Protective efficacy of reverse genetics based on inactivated American and Asian neuraminidase DIVA marker vaccines against highly pathogenic H5N1 avian influenza viruses in chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Asian H5N1 highly pathogenic avian influenza has become endemic in several countries, and vaccination is commonly being used. Vaccination can affect surveillance, and therefore there is considerable interest in DIVA (differentiate infected from vaccinated animals) vaccine strategies. Using reverse...

  3. 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...

  4. Suboptimal protection against H5N1 highly pathogenic avian influenza viruses from Vietnam in ducks vaccinated with commercial poultry vaccines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Highly pathogenic (HP) H5N1 avian influenza (AI) viruses continue to circulate in Asia and other regions of the world. Vaccination is used as part of H5N1 HPAI control programs in many countries; however, eradication of the disease has not been possible due to the emergence and spread of new viruses...

  5. 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 ...

  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)

    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...

  7. Highly Pathogenic Avian Influenza A(H5N8) Viruses Reintroduced into South Korea by Migratory Waterfowl, 2014–2015

    PubMed Central

    Kwon, Jung-Hoon; Lee, Dong-Hun; Swayne, David E.; Noh, Jin-Yong; Yuk, Seong-Su; Erdene-Ochir, Tseren-Ochir; Hong, Woo-Tack; Jeong, Jei-Hyun; Jeong, Sol; Gwon, Gyeong-Bin

    2016-01-01

    Highly pathogenic avian influenza A(H5N8) viruses were isolated from migratory waterfowl in South Korea during fall 2014–winter 2015, a recurrence after initial introduction in winter 2014. These reappeared viruses were phylogenetically distinct from isolates circulating in poultry farms in South Korea. PMID:26890406

  8. Determination of efficacious vaccine seed strains for use against Egyptian H5N1 highly pathogenic avian influenza viruses through antigenic cartography and in vivo challenge studies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since 2006, there have been reported outbreaks of H5N1 highly pathogenic avian influenza (HPAI) in vaccinated chickens in Africa and Asia. This study provides experimental data for selection of efficacious H5N1 vaccine seed strains against recently circulating strains of H5N1 HPAI viruses in Egypt....

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

    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. Exposure to lentogenic NDV, either from live vaccines or field strains, is nearly unavoidable for poultry, and co-infections with low pathogenic (LP) AIV are expected to ...

  10. 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, ...

  11. H5N1 highly pathogenic avian influenza virus experimental infection trials in wild birds: what have we learned and what questions remain

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prior to 2002, there were very few reports of highly pathogenic avian influenza (HPAI) virus infections in wild birds. Since 2002; however, a variety of wild avian species have died from infection with Asian lineage H5N1 HPAI viruses and a growing body of evidence suggests migratory waterfowl may h...

  12. Thermal inactivation of H5N2 high pathogenicity avian influenza virus in dried egg white with 7.5% moisture

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High pathogenicity avian influenza viruses (HPAIV) cause severe systemic disease with high mortality in chickens. Isolation of HPAIV from the internal contents of chicken eggs has been reported, and this is cause for concern because HPAIV can be spread by movement of poultry products during marketi...

  13. IMPACT OF DIFFERENT HUSBANDRY CONDITIONS ON CONTACT AND AIRBORNE TRANSMISSION OF H5N1 HIGHLY PATHOGENIC AVIAN INFLUENZA VIRUS TO CHICKENS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Typically highly pathogenic avian influenza (HPAI) viruses spread very rapidly among chickens within sheds. However, the spread was slower than expected for the initial 10 days of the index farm in Japan during 2004. This slow spread as well as the lack of gross lesions, clinical signs or high morta...

  14. 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...

  15. Mucosal vaccination with a codon-optimized hemagglutinin gene expressed by attenuated Salmonella elicits a protective immune response in chickens against highly pathogenic avian influenza

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The purpose of this study was to evaluate the protection of two attenuated Salmonella enteria serovar typhimurium strains expressing the hemagglutinin (HA) gene from a highly pathogenic avian influenza (HPAI) H5N1 (A/whooper swan/Mongolia/3/2005), under control of the anaerobically inducible nir15 p...

  16. 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...

  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. Highly pathogenic avian influenza A(H5N8) viruses reintroduced into South Korea by migratory waterfowl, 2014–2015

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Highly pathogenic avian influenza A(H5N8) viruses were isolated from migratory waterfowl in South Korea during all 2014–winter 2015, a recurrence after initial introduction in winter 2014. These reappeared viruses were phylogenetically distinct from isolates circulating in poultry farms in South Kor...

  19. Role of immune-related host gene responses in the pathobiology of H5N1 highly pathogenic avian influenza in ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Asian highly pathogenic avian influenza (HPAI) H5N1 viruses have changed from producing mild respiratory infections in ducks to some strains causing severe disease and mortality. In this study we examined host response to infection with HPAI H5N1 viruses in ducks. With the use of a whole genom...

  20. Efficacy of commercial vaccines in protecting chickens and ducks against H5N1 highly pathogenic avian influenza viruses from Vietnam

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Highly pathogenic (HP) H5N1 avian influenza (AI) viruses continue to circulate in Asia and have spread to other regions of the world. Though attempts at eradication of the viruses during various outbreaks have been successful for short periods of time, new strains of H5N1 viruses continue to emerge...

  1. Pekin and Muscovy ducks respond differently to vaccination with a H5N1 highly pathogenic avian influenza (HPAI) commercial inactivated vaccine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Domestic ducks are key intermediates in the transmission of H5N1 highly pathogenic avian influenza (HPAI) viruses, and therefore are included in vaccination programs to control H5N1 HPAI. Although vaccination has proven effective in protecting ducks against disease, different species of domestic duc...

  2. Comparison of pig and ferret models for evaluation of respiratory versus alimentary transmission of H5N1 high pathogenicity avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: H5N1 high pathogenicity avian influenza viruses (HPAIV) have caused over 300 human infections and over 200 deaths since 2003. The majority of the cases have involved close direct or indirect contact with infected poultry but a few cases have incriminated consumption of uncooked poultry p...

  3. Infectious and lethal doses of H5N1 highly pathogenic avian influenza virus for house sparrows (Passer domesticus) and rock pigeons (Columbia livia)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Terrestrial wild birds commonly associated with poultry farms have the potential to contribute to the spread of H5N1 highly pathogenic avian influenza virus within or between poultry facilities or between domesticated and wild bird populations. This potential, however, varies between species and is...

  4. Detection of H5 and H7 highly pathogenic avian influenza virus with lateral flow devices: performance with healthy, sick and dead chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rapid detection of highly pathogenic avian influenza virus (HPAIV) in the field is critical for effective disease control and to differentiate it from other diseases, such as Newcastle disease. Lateral flow devices (LFD) are commercially available and provide a fast, highly specific, on-site test fo...

  5. Pathogenic significance of alpha-N-acetylgalactosaminidase activity found in the hemagglutinin of influenza virus.

    PubMed

    Yamamoto, Nobuto; Urade, Masahiro

    2005-04-01

    Serum vitamin D3-binding protein (Gc protein) is the precursor for the principal macrophage activating factor (MAF). The precursor activity of serum Gc protein was reduced in all influenza virus-infected patients. These patient sera contained alpha-N-acetylgalactosaminidase (Nagalase) that deglycosylates Gc protein. Deglycosylated Gc protein cannot be converted to MAF, thus it loses the MAF precursor activity, leading to immunosuppression. An influenza virus stock contained a large amount of Nagalase activity. A sucrose gradient centrifugation analysis of the virus stock showed that the profile of Nagalase activity corresponds to that of hemagglutinating activity. When these gradient fractions were treated with 0.01% trypsin for 30 min, the Nagalase activity of each fraction increased significantly, suggesting that the Nagalase activity resides on an outer envelope protein of the influenza virion and is enhanced by the proteolytic process. After disruption of influenza virions with sodium deoxycholate, fractionation of the envelope proteins with mannose-specific lectin affinity column along with electrophoretic analysis of the Nagalase peak fraction revealed that Nagalase is the intrinsic component of the hemagglutinin (HA). Cloned HA protein exhibited Nagalase activity only if treated with trypsin. Since both fusion capacity and Nagalase activity of HA protein are expressed by proteolytic cleavage, Nagalase activity appears to be an enzymatic basis for the fusion process. Thus, Nagalase plays dual roles in regulating both infectivity and immunosuppression. PMID:15848273

  6. Comparative susceptibility of waterfowl and gulls to highly pathogenic avian influenza H5N1 virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Wild avian species in the Orders Anseriformes (ducks, geese, swans) and Charadriiformes (gulls, terns, shorebirds) have traditionally been considered the natural reservoirs for avian influenza viruses (AIV) and morbidity or mortality is rarely associated with AIV infection in these hosts. However, ...

  7. Use of interferon treatment to protect chickens against highly pathogenic avian influenza

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza (AI) is a significant public health concern and serious economic threat to the commercial poultry industry worldwide. While properly matched vaccines can be effective at limiting morbidity and mortality, the use of therapeutics in veterinary animals to combat this disease are relativ...

  8. Intranasal application of alpha interferon reduces morbidity associated with low pathogenic avian influenza infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Type I interferons, including interferon alpha (IFN-alpha), are expressed rapidly after viral infection, and represent a first line of defense initiated by the innate immune response. Following infection of chickens with avian influenza virus (AIV), transcription of IFN-alpha is quickly up regulate...

  9. Characterization of low pathogenicity avian influenza viruses isolated from wild birds in Mongolia 2005 through 2007

    Technology Transfer Automated Retrieval System (TEKTRAN)

    During 2005, 2006 and 2007 2,139 specimens representing 4,077 individual birds of 45 species were tested for avian influenza virus (AIV) as part of a wild bird AIV monitoring program conducted in Mongolia. Samples collected in 2005 were tested by virus isolation directly, samples from 2006 and 2007...

  10. Cross reactive cellular immune responses in chickens previously exposed to low pathogenic avian influenza

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza (AI) infection in poultry can result in high morbidity and mortality, and negatively affect international trade. Because most AI vaccines used for poultry are inactivated, our knowledge of immunity against AI is based largely on humoral immune responses. In fact, little is known abo...

  11. Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes.

    PubMed

    Monsalvo, Ana Clara; Batalle, Juan P; Lopez, M Florencia; Krause, Jens C; Klemenc, Jennifer; Hernandez, Johanna Zea; Maskin, Bernardo; Bugna, Jimena; Rubinstein, Carlos; Aguilar, Leandro; Dalurzo, Liliana; Libster, Romina; Savy, Vilma; Baumeister, Elsa; Aguilar, Liliana; Cabral, Graciela; Font, Julia; Solari, Liliana; Weller, Kevin P; Johnson, Joyce; Echavarria, Marcela; Edwards, Kathryn M; Chappell, James D; Crowe, James E; Williams, John V; Melendi, Guillermina A; Polack, Fernando P

    2011-02-01

    Pandemic influenza viruses often cause severe disease in middle-aged adults without preexisting comorbidities. The mechanism of illness associated with severe disease in this age group is not well understood. Here we find preexisting serum antibodies that cross-react with, but do not protect against, 2009 H1N1 influenza virus in middle-aged adults. Nonprotective antibody is associated with immune complex-mediated disease after infection. We detected high titers of serum antibody of low avidity for H1-2009 antigen, and low-avidity pulmonary immune complexes against the same protein, in severely ill individuals. Moreover, C4d deposition--a marker of complement activation mediated by immune complexes--was present in lung sections of fatal cases. Archived lung sections from middle-aged adults with confirmed fatal influenza 1957 H2N2 infection revealed a similar mechanism of illness. These observations provide a previously unknown biological mechanism for the unusual age distribution of severe cases during influenza pandemics. PMID:21131958

  12. The performance characteristics of lateral flow devices with 2 strains of highly pathogenic avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lateral flow devices (LFD) are commercially available and provide a fast, highly specific, on-site test for avian influenza. Because of the low analytic sensitivity of LFD tests at low virus concentrations, targeted sampling of sick and dead birds has been proposed in order to increase detection pr...

  13. Systemic virus distribution and host responses in brain and intestine of chickens infected with low pathogenic or high pathogenic avian influenza virus

    PubMed Central

    2012-01-01

    Background Avian influenza virus (AIV) is classified into two pathotypes, low pathogenic (LP) and high pathogenic (HP), based on virulence in chickens. Differences in pathogenicity between HPAIV and LPAIV might eventually be related to specific characteristics of strains, tissue tropism and host responses. Methods To study differences in disease development between HPAIV and LPAIV, we examined the first appearance and eventual load of viral RNA in multiple organs as well as host responses in brain and intestine of chickens infected with two closely related H7N1 HPAIV or LPAIV strains. Results Both H7N1 HPAIV and LPAIV spread systemically in chickens after a combined intranasal/intratracheal inoculation. In brain, large differences in viral RNA load and host gene expression were found between H7N1 HPAIV and LPAIV infected chickens. Chicken embryo brain cell culture studies revealed that both HPAIV and LPAIV could infect cultivated embryonic brain cells, but in accordance with the absence of the necessary proteases, replication of LPAIV was limited. Furthermore, TUNEL assay indicated apoptosis in brain of HPAIV infected chickens only. In intestine, where endoproteases that cleave HA of LPAIV are available, we found minimal differences in the amount of viral RNA and a large overlap in the transcriptional responses between HPAIV and LPAIV infected chickens. Interestingly, brain and ileum differed clearly in the cellular pathways that were regulated upon an AI infection. Conclusions Although both H7N1 HPAIV and LPAIV RNA was detected in a broad range of tissues beyond the respiratory and gastrointestinal tract, our observations indicate that differences in pathogenicity and mortality between HPAIV and LPAIV could originate from differences in virus replication and the resulting host responses in vital organs like the brain. PMID:22390870

  14. Avian influenza surveillance reveals presence of low pathogenic avian influenza viruses in poultry during 2009-2011 in the West Bengal State, India

    PubMed Central

    2012-01-01

    Introduction More than 70 outbreaks of the highly pathogenic avian influenza (HPAI) H5N1 have been reported in poultry in the western and north-eastern parts of India. Therefore, in view of the recent HPAI H5N1 outbreaks in poultry, active AI surveillance encompassing wild, resident, migratory birds and poultry was undertaken during 2009–2011 in the State of West Bengal. Methods A total of 5722 samples were collected from West Bengal; 3522 samples (2906 fecal droppings + 616 other environmental samples) were from migratory birds and 2200 samples [1604 tracheal, cloacal swabs, environmental samples, tissue samples + 596 blood (serum)] were from domestic ducks and poultry. All tracheal, cloacal and environmental samples were processed for virus isolation. Virus isolates were detected using hemagglutination assay and identified using hemagglutination inhibition (HI) and reverse transcriptase polymerase chain reaction (RT-PCR) assays. Sequencing and phylogenetic analysis of partial region of the hemagglutinin and neuraminidase genes was done. Intravenous pathogenicity index assays were performed in chickens to assess pathogenicity of AI virus isolates. Serum samples were tested for detection of antibodies against AI viruses using HI assay. Results A total of 57 AI H9N2, 15 AI H4N6 and 15 Newcastle Disease (NDV) viruses were isolated from chickens, from both backyard and wet poultry markets; AI H4N6 viruses were isolated from backyard chickens and domestic ducks. Characterization of AI H9N2 and H4N6 viruses revealed that they were of low pathogenicity. Domestic ducks were positive for antibodies against H5 and H7 viruses while chickens were positive for presence of antibodies against AI H9N2 and NDV. Conclusions In the current scenario of HPAI H5N1 outbreaks in West Bengal, this report shows presence of low pathogenic AI H9N2 and H4N6 viruses in chickens and domestic ducks during the period 2009–2011. This is the first report of isolation of H4N6 from India

  15. Determining the Phylogenetic and Phylogeographic Origin of Highly Pathogenic Avian Influenza (H7N3) in Mexico

    PubMed Central

    Lu, Lu; Lycett, Samantha J.; Leigh Brown, Andrew J.

    2014-01-01

    Highly pathogenic (HP) avian influenza virus (AIV) H7N3 outbreaks occurred 3 times in the Americas in the past 10 years and caused severe economic loss in the affected regions. In June/July 2012, new HP H7N3 outbreaks occurred at commercial farms in Jalisco, Mexico. Outbreaks continued to be identified in neighbouring states in Mexico till August 2013. To explore the origin of this outbreak, time resolved phylogenetic trees were generated from the eight segments of full-length AIV sequences in North America using BEAST. Location, subtype, avian host species and pathogenicity were modelled as discrete traits upon the trees using continuous time Markov chains. A further joint analysis among segments was performed using a hierarchical phylogenetic model (HPM) which allowed trait rates (location, subtype, host species) to be jointly inferred across different segments. The complete spatial diffusion process was visualised through virtual globe software. Our result indicated the Mexico HP H7N3 originated from the large North America low pathogenicity AIV pool through complicated reassortment events. Different segments were contributed by wild waterfowl from different N. American flyways. Five of the eight segments (HA, NA, NP, M, NS) were introduced from wild birds migrating along the central North American flyway, and PB2, PB1 and PA were introduced via the western North American flyway. These results highlight a potential role for Mexico as a hotspot of virus reassortment as it is where wild birds from different migration routes mix during the winter. PMID:25226523

  16. Shedding of a Low Pathogenic Avian Influenza Virus in a Common Synanthropic Mammal – The Cottontail Rabbit

    PubMed Central

    Root, J. Jeffrey; Shriner, Susan A.; Bentler, Kevin T.; Gidlewski, Thomas; Mooers, Nicole L.; Spraker, Terry R.; VanDalen, Kaci K.; Sullivan, Heather J.; Franklin, Alan B.

    2014-01-01

    Background Cottontails (Sylvilagus spp.) are common mammals throughout much of the U.S. and are often found in peridomestic settings, potentially interacting with livestock and poultry operations. If these animals are susceptible to avian influenza virus (AIV) infections and shed the virus in sufficient quantities they may pose a risk for movement of avian influenza viruses between wildlife and domestic animals in certain situations. Methodology/Principal Findings To assess the viral shedding potential of AIV in cottontails, we nasally inoculated fourteen cottontails with a low pathogenic AIV (H4N6). All inoculated cottontails shed relatively large quantities of viral RNA both nasally (≤106.94 PCR EID50 equivalents/mL) and orally (≤105.09 PCR EID50 equivalents/mL). However, oral shedding tended to decline more quickly than did nasal shedding. No animals showed any obvious signs of disease throughout the study. Evidence of a serological response was found in all infected rabbits at 22 days post infection in convalescent sera. Conclusions/Significance To our knowledge, cottontails have not been previously assessed for AIV shedding. However, it was obvious that they shed AIV RNA extensively via the nasal and oral routes. This is significant, as cottontails are widely distributed throughout the U.S. and elsewhere. These mammals are often found in highly peridomestic situations, such as farms, parks, and suburban neighborhoods, often becoming habituated to human activities. Thus, if infected these mammals could easily transport AIVs short distances. PMID:25111780

  17. Living with avian FLU--Persistence of the H5N1 highly pathogenic avian influenza virus in Egypt.

    PubMed

    Njabo, Kevin Yana; Zanontian, Linda; Sheta, Basma N; Samy, Ahmed; Galal, Shereen; Schoenberg, Frederic Paik; Smith, Thomas B

    2016-05-01

    H5N1 highly pathogenic avian influenza virus (HPAIV) continues to cause mortality in poultry and threaten human health at a panzootic scale in Egypt since it was reported in 2006. While the early focus has been in Asia, recent evidence suggests that Egypt is an emerging epicenter for the disease. Despite control measures, epizootic transmission of the disease continues. Here, we investigate the persistence of HPAIV across wild passerine birds and domestic poultry between 2009 and 2012 and the potential risk for continuous viral transmission in Egypt. We use a new weighted cross J-function to investigate the degree and spatial temporal nature of the clustering between sightings of infected birds of different types, and the risk of infection associated with direct contact with infected birds. While we found no infection in wild birds, outbreaks occurred year round between 2009 and 2012, with a positive interaction between chickens and ducks. The disease was more present in the years 2010 and 2011 coinciding with the political unrest in the country. Egypt thus continues to experience endemic outbreaks of avian influenza HPAIV in poultry and an increased potential risk of infection to other species including humans. With the current trends, the elimination of the HPAIV infection is highly unlikely without a complete revamp of current policies. The application of spatial statistics techniques to these types of data may help us to understand the characteristics of the disease and may subsequently allow practitioners to explore possible preventive solutions. PMID:27066713

  18. Analysis of the Contrasting Pathogenicities Induced by the D222G Mutation in 1918 and 2009 Pandemic Influenza A Viruses

    PubMed Central

    2015-01-01

    In 2009, the D222G mutation in the hemagglutinin (HA) glycoprotein of pandemic H1N1 influenza A virus was found to correlate with fatal and severe human infections. Previous static structural analysis suggested that, unlike the H1N1 viruses prevalent in 1918, the mutation did not compromise binding to human α2,6-linked glycan receptors, allowing it to transmit efficiently. Here we investigate the interconversion mechanism between two predicted binding modes in both 2009 and 1918 HAs, introducing a highly parallel intermediate network search scheme to construct kinetically relevant pathways efficiently. Accumulated mutations at positions 183 and 224 that alter the size of the binding pocket are identified with the fitness of the 2009 pandemic virus carrying the D222G mutation. This result suggests that the pandemic H1N1 viruses could gain binding affinity to the α2,3-linked glycan receptors in the lungs, usually associated with highly pathogenic avian influenza, without compromising viability. PMID:26321885

  19. Antigenic and Genetic Evolution of Low-Pathogenicity Avian Influenza Viruses of Subtype H7N3 following Heterologous Vaccination

    PubMed Central

    Xu, Yifei; Long, Li-Ping; Capua, Ilaria; Wan, Xiu-Feng

    2014-01-01

    Outbreaks of low-pathogenicity avian influenza (LPAI) viruses of the H7N3 subtype were first detected in Italy in October 2002, and the virus continued to circulate between 2002 and 2004 in a densely populated poultry area in the northeast portion of that country. This virus circulated in unvaccinated and vaccinated poultry farms, and the infection was controlled in August 2003 by culling, control of movements, improved biosecurity, and heterologous vaccination. In 2004, H7N3 reoccurred in vaccinated poultry farms in which infection had been successfully controlled by the vaccination program. To shed light on this occurrence and the temporal pattern and genetic basis of antigenic drift for avian influenza viruses (AIVs) in the absence and presence of heterologous vaccination, a collection of H7N3 viruses isolated in 2002 and 2004 were characterized genetically and antigenically. Molecular analysis showed that viruses isolated in the 2004 outbreaks after the implementation of vaccination had acquired specific amino acid signatures, most of which were located at reported antibody binding sites of the hemagglutinin (HA) protein. Antigenic characterization of these 2004 isolates showed that they were antigenically different from those isolated prior to the implementation of vaccination. This is the first report on antigenic and genetic evolution of H7 LPAI viruses following the application of heterologous vaccination in poultry. These findings may have an impact on control strategies to combat AI infections in poultry based on vaccination. PMID:24554694

  20. 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. PMID:27030920

  1. Wild Birds and Increased Transmission of Highly Pathogenic Avian Influenza (H5N1) among Poultry, Thailand

    PubMed Central

    Keawcharoen, Juthatip; van den Broek, Jan; Bouma, Annemarie; Tiensin, Thanawat; Osterhaus, Albert D.M.E

    2011-01-01

    Since the outbreaks of highly pathogenic avian influenza (HPAI) subtype H5N1 virus, wild birds have been suspected of transmitting this virus to poultry. On January 23, 2004, the Ministry of Public Health in Thailand informed the World Health Organization of an avian influenza A (H5N1) outbreak. To determine the epidemiology of this viral infection and its relation to poultry outbreaks in Thailand from 2004 through 2007, we investigated how wild birds play a role in transmission. A total of 24,712 serum samples were collected from migratory and resident wild birds. Reverse transcription PCR showed a 0.7% HPAI (H5N1) prevalence. The highest prevalence was observed during January–February 2004 and March–June 2004, predominantly in central Thailand, which harbors most of the country’s poultry flocks. Analysis of the relationship between poultry and wild bird outbreaks was done by using a nonhomogeneous birth and death statistical model. Transmission efficiency among poultry flocks was 1.7× higher in regions with infected wild birds in the given or preceding month. The joint presence of wild birds and poultry is associated with increased spread among poultry flocks. PMID:21749762

  2. Ostrich ( Struthio camelus ) Infected with H5N8 Highly Pathogenic Avian Influenza Virus in South Korea in 2014.

    PubMed

    Kim, Hye-Ryoung; Kwon, Yong-Kuk; Lee, Youn-Jeong; Kang, Hyun-Mi; Lee, Eun-Kyoung; Song, Byung-Min; Jung, Suk-Chan; Lee, Kyung-Hyun; Lee, Hyun-Kyoung; Baek, Kang-Hyun; Bae, You-Chan

    2016-06-01

    Highly pathogenic avian influenza (HPAI) virus of the H5N8 subtype was isolated from a young ostrich in South Korea in March 2014. Clinical signs characterized by anorexia, depression, and signs of nervousness were observed. The isolated A/ostrich/Korea/H829/2014 (H5N8) virus had a cleavage site motif containing multiple basic amino acids, typical of HPAI virus. The phylogenetic tree of the hemagglutinin gene of the H5 HPAI virus showed that this ostrich H5N8 virus belongs to clade 2.3.4.4 viruses together with H5N8 strains isolated from ducks and wild birds in South Korea in 2014. Pathologically, redness of pancreas, enlargement and hemorrhage of spleen, friability of brain, and hydropericardium were prominently found. Histologic legions were observed in pancreas, spleen, liver, lung, heart, and brain, and influenza A nucleoproteins were detected in the same organs by immunohistochemistry. Other ostriches farmed together in open camps were not infected with HPAI virus based on the serologic and virologic tests. The findings indicate that ostriches are susceptible to H5N8 HPAI virus, but this virus does not spread efficiently among ratites. PMID:27309301

  3. When private actors matter: Information-sharing network and surveillance of Highly Pathogenic Avian Influenza in Vietnam.

    PubMed

    Delabouglise, A; Dao, T H; Truong, D B; Nguyen, T T; Nguyen, N T X; Duboz, R; Fournié, G; Antoine-Moussiaux, N; Grosbois, V; Vu, D T; Le, T H; Nguyen, V K; Salem, G; Peyre, M

    2015-07-01

    The effectiveness of animal health surveillance systems depends on their capacity to gather sanitary information from the animal production sector. In order to assess this capacity we analyzed the flow of sanitary information regarding Highly Pathogenic Avian Influenza (HPAI) suspicions in poultry in Vietnam. Participatory methods were applied to assess the type of actors and likelihood of information sharing between actors in case of HPAI suspicion in poultry. While the reporting of HPAI suspicions is mandatory, private actors had more access to information than public actors. Actors of the upstream sector (medicine and feed sellers) played a key role in the diffusion of information. The central role of these actors and the influence of the information flow on the adoption by poultry production stakeholders of behaviors limiting (e.g. prevention measures) or promoting disease transmission (e.g. increased animal movements) should be accounted for in the design of surveillance and control programs. PMID:25847263

  4. Anatidae Migration in the Western Palearctic and Spread of Highly Pathogenic Avian Influenza H5N1 Virus

    PubMed Central

    Xiao, Xiangming; Domenech, Joseph; Lubroth, Juan; Martin, Vincent; Slingenbergh, Jan

    2006-01-01

    During the second half of 2005, highly pathogenic avian influenza (HPAI) H5N1 virus spread rapidly from central Asia to eastern Europe. The relative roles of wild migratory birds and the poultry trade are still unclear, given that little is yet known about the range of virus hosts, precise movements of migratory birds, or routes of illegal poultry trade. We document and discuss the spread of the HPAI H5N1 virus in relation to species-specific flyways of Anatidae species (ducks, geese, and swans) and climate. We conclude that the spread of HPAI H5N1 virus from Russia and Kazakhstan to the Black Sea basin is consistent in space and time with the hypothesis that birds in the Anatidae family have seeded the virus along their autumn migration routes. PMID:17283613

  5. Insight into Alternative Approaches for Control of Avian Influenza in Poultry, with Emphasis on Highly Pathogenic H5N1

    PubMed Central

    Abdelwhab, E. M.; Hafez, Hafez M.

    2012-01-01

    Highly pathogenic avian influenza virus (HPAIV) of subtype H5N1 causes a devastating disease in poultry but when it accidentally infects humans it can cause death. Therefore, decrease the incidence of H5N1 in humans needs to focus on prevention and control of poultry infections. Conventional control strategies in poultry based on surveillance, stamping out, movement restriction and enforcement of biosecurity measures did not prevent the virus spreading, particularly in developing countries. Several challenges limit efficiency of the vaccines to prevent outbreaks of HPAIV H5N1 in endemic countries. Alternative and complementary approaches to reduce the current burden of H5N1 epidemics in poultry should be encouraged. The use of antiviral chemotherapy and natural compounds, avian-cytokines, RNA interference, genetic breeding and/or development of transgenic poultry warrant further evaluation as integrated intervention strategies for control of HPAIV H5N1 in poultry. PMID:23202521

  6. Transmission of an H5N8-Subtype Highly Pathogenic Avian Influenza Virus from Infected Hens to Laid Eggs.

    PubMed

    Uchida, Yuko; Takemae, Nobuhiro; Tanikawa, Taichiro; Kanehira, Katsushi; Saito, Takehiko

    2016-06-01

    We showed here that an H5N8-subtype highly pathogenic avian influenza virus (HPAIV) was transmitted to both the internal contents and shells of eggs laid by white leghorn hens experimentally infected with the virus. Seven of eight HPAIV-infected hens laid eggs until 4 days postinoculation (dpi). The mean number of eggs laid per head daily decreased significantly from 0.58 before inoculation to 0.18 after viral inoculation. The virus was detected in the eggs laid by three of the seven hens. Viral transmission was detectable beginning on 3 dpi, and virus titers in tracheal and cloacal swabs from the hens that laid the contaminated eggs exceeded 2.9 log10 EID50. The level of viral replication and its timing when virus replicates enough to be detected in oviduct after virus inoculation appear to be key factors in the transmission of H5N8 HPAIV from infected hens to laid eggs. PMID:27309286

  7. Antigenic and genetic diversity of highly pathogenic avian influenza A (H5N1) viruses isolated in Egypt.

    PubMed

    Balish, Amanda L; Davis, C Todd; Saad, Magdi D; El-Sayed, Nasr; Esmat, Hala; Tjaden, Jeffrey A; Earhart, Kenneth C; Ahmed, Lu'ay E; Abd El-Halem, Mohamed; Ali, Abdel Hakem M; Nassif, Samir A; El-Ebiary, Elham A; Taha, M; Aly, Mona M; Arafa, Abdelstattar; O'Neill, Eduardo; Xiyan, Xu; Cox, Nancy J; Donis, Ruben O; Klimov, Alexander I

    2010-03-01

    Highly pathogenic avian influenza A virus (H5N1) has diverged antigenically and genetically since its initial detection in Asia in 1997. Viruses belonging to clade 2.2 in particular have been reported in numerous countries with the majority occurring in Egypt. Previous reports identified antigenic similarities between viruses belonging to clade 2.2. However, poultry and human viruses isolated in northern Egypt during 2007 and 2008 were found to be antigenically distinct from other clade 2.2 viruses from this country. Genetic analysis of the hemagglutinin revealed a high degree of nucleotide and amino acid divergence. The antigenic changes in Egyptian viruses isolated during 2007-08 necessitated that two of these strains be considered as potential H5N1 pre-pandemic vaccine candidates. PMID:20521654

  8. Epidemiological consequences of an incursion of highly pathogenic H5N1 avian influenza into the British poultry flock

    PubMed Central

    Sharkey, Kieran J; Bowers, Roger G; Morgan, Kenton L; Robinson, Susan E; Christley, Robert M

    2007-01-01

    Highly pathogenic avian influenza and in particular the H5N1 strain has resulted in the culling of millions of birds and continues to pose a threat to poultry industries worldwide. The recent outbreak of H5N1 in the UK highlights the need for detailed assessment of the consequences of an incursion and of the efficacy of control strategies. Here, we present results from a model of H5N1 propagation within the British poultry industry. We find that although the majority of randomly seeded incursions do not spread beyond the initial infected premises, there is significant potential for widespread infection. The efficacy of the European Union strategy for disease control is evaluated and our simulations emphasize the pivotal role of duck farms in spreading H5N1. PMID:17956849

  9. The space-time clustering of highly pathogenic avian influenza (HPAI) H5N1 outbreaks in Bangladesh.

    PubMed

    Ahmed, S S U; Ersbøll, A K; Biswas, P K; Christensen, J P

    2010-06-01

    Bangladesh faced two epidemic waves of highly pathogenic avian influenza (HPAI) H5N1 in two consecutive years. The peaks of the waves were observed in February-July 2007 and January-April 2008, respectively. We examined the spatial and temporal patterns of the 293 outbreaks in 143 subdistricts in 2007 and 2008. Global clustering assessed by K-function was seen at distances 150-300 km between subdistricts. Significant local clusters were detected by space-time scan statistics. In both waves, significant primary clusters of HPAI outbreaks were identified in the central part of the country dominated by commercial production systems and in the northwestern part primarily in backyard production systems. Secondary clusters varied from the northwestern part in 2007 and the southern part in 2008. The findings are highly relevant for the successful planning and implementation of control, prevention and surveillance strategies by highlighting areas where detailed investigations should be initiated. PMID:20109257

  10. Insertion of a multibasic cleavage site in the haemagglutinin of human influenza H3N2 virus does not increase pathogenicity in ferrets

    PubMed Central

    Schrauwen, Eefje J. A.; Bestebroer, Theo M.; Munster, Vincent J.; de Wit, Emmie; Herfst, Sander; Rimmelzwaan, Guus F.; Osterhaus, Albert D. M. E.

    2011-01-01

    A multibasic cleavage site (MBCS) in the haemagglutinin (HA) protein of influenza A virus is a key determinant of pathogenicity in chickens, and distinguishes highly pathogenic avian influenza (HPAI) viruses from low pathogenic avian influenza viruses (LPAI). An MBCS has only been detected in viruses of the H5 and H7 subtypes. Here we investigated the phenotype of a human H3N2 virus with an MBCS in HA. Insertion of an MBCS in the H3N2 virus resulted in cleavage of HA and efficient replication in Madin–Darby canine kidney cells in the absence of exogenous trypsin in vitro, similar to HPAI H5N1 virus. However, studies in ferrets demonstrated that insertion of the MBCS into HA did not result in increased virus shedding, cellular host range, systemic replication or pathogenicity, as compared with wild-type virus. This study indicates that acquisition of an MBCS alone is insufficient to increase pathogenicity of a prototypical seasonal human H3N2 virus. PMID:21346026

  11. First reported detection of a low pathogenicity avian influenza virus subtype H9 infection in domestic fowl in England.

    PubMed

    Parker, C D; Reid, S M; Ball, A; Cox, W J; Essen, S C; Hanna, A; Mahmood, S; Slomka, M J; Irvine, R M; Brown, I H

    2012-10-13

    In December 2010, infection with a H9N1 low pathogenicity avian influenza (LPAI) virus was detected in a broiler breeder flock in East Anglia. Disease suspicion was based on acute drops in egg production in two of four sheds on the premises, poor egg shell quality and evidence of diarrhoea. H9N1 LPAI virus infection was confirmed by real-time reverse transcription PCR. Sequencing revealed high nucleotide identity of 93.6 per cent and 97.9 per cent with contemporary North American H9 and Eurasian N1 genes, respectively. Attempted virus isolation in embryonated specific pathogen free (SPF) fowls' eggs was unsuccessful. Epidemiological investigations were conducted to identify the source of infection and any onward spread. These concluded that infection was restricted to the affected premises, and no contacts or movements of poultry, people or fomites could be attributed as the source of infection. However, the infection followed a period of extremely cold weather and snow which impacted on the biosecurity protocols on site, and also led to increased wild bird activity locally, including waterfowl and game birds around the farm buildings. Analysis of the N1 gene sequence suggested direct introduction from wild birds. Although H9 infection in poultry is not notifiable, H9N2 LPAI viruses have been associated with production and mortality episodes in poultry in many parts of Asia and the Middle East. In the present H9N1 outbreak, clinical signs were relatively mild in the poultry with no mortality, transient impact on egg production and no indication of zoonotic spread. However, this first reported detection of H9 LPAI virus in chickens in England was also the first H9 UK poultry case for 40 years, and vindicates the need for continued vigilance and surveillance of avian influenza viruses in poultry populations. PMID:22949546

  12. Broadly protective adenovirus-based multivalent vaccines against highly pathogenic avian influenza viruses for pandemic preparedness.

    PubMed

    Vemula, Sai V; Ahi, Yadvinder S; Swaim, Anne-Marie; Katz, Jacqueline M; Donis, Ruben; Sambhara, Suryaprakash; Mittal, Suresh K

    2013-01-01

    Recurrent outbreaks of H5, H7 and H9 avian influenza viruses in domestic poultry accompanied by their occasional transmission to humans have highlighted the public health threat posed by these viruses. Newer vaccine approaches for pandemic preparedness against these viruses are needed, given the limitations of vaccines currently approved for H5N1 viruses in terms of their production timelines and the ability to induce protective immune responses in the absence of adjuvants. In this study, we evaluated the feasibility of an adenovirus (AdV)-based multivalent vaccine approach for pandemic preparedness against H5, H7 and H9 avian influenza viruses in a mouse model. Replication-defective AdV vectors expressing hemagglutinin (HA) from different subtypes and nucleoprotein (NP) from one subtype induced high levels of humoral and cellular immune responses and conferred protection against virus replication following challenge with H5, H7 and H9 avian influenza virus subtypes. Inclusion of HA from the 2009 H1N1 pandemic virus in the vaccine formulation further broadened the vaccine coverage. Significantly high levels of HA stalk-specific antibodies were observed following immunization with the multivalent vaccine. Inclusion of NP into the multivalent HA vaccine formulation resulted in the induction of CD8 T cell responses. These results suggest that a multivalent vaccine strategy may provide reasonable protection in the event of a pandemic caused by H5, H7, or H9 avian influenza virus before a strain-matched vaccine can be produced. PMID:23638099

  13. REMOTE SENSING, ECOLOGICAL VARIABLES, AND WILD BIRD MIGRATION RELATED TO OUTBREAKS OF HIGHLY PATHOGENIC H5N1 AVIAN INFLUENZA1

    PubMed Central

    Xiao, Xiangming; Gilbert, Marius; Slingenbergh, Jan; Lei, Fumin; Boles, Stephen

    2008-01-01

    Outbreaks of highly pathogenic avian influenza (HPAI) H5N1 subtype have occurred in many countries across Asia, Europe, and Africa since 2003. Better understanding of the ecology and risk factors of HPAI is critical for surveillance, risk assessment, and public health policy. We introduce satellite remote sensing as one important tool, and highlight the potential of using satellite images to monitor dynamics of climate and landscapes that are related to wild bird migration and agriculture in the context of avian influenza transmission. PMID:17347392

  14. Vaccine Protection of Turkeys Against H5N1 Highly Pathogenic Avian Influenza Virus with a Recombinant Turkey Herpesvirus Expressing the Hemagglutinin Gene of Avian Influenza.

    PubMed

    Kapczynski, Darrell R; Dorsey, Kristi; Chrzastek, Klaudia; Moraes, Mauro; Jackwood, Mark; Hilt, Debra; Gardin, Yannick

    2016-06-01

    Outbreaks of H5 highly pathogenic avian influenza (HPAI) in commercial poultry are a constant threat to animal health and food supplies. While vaccination can enhance protection and reduce the spread of disease, there is considerable evidence that the level of immunity required for protection varies by subtype and virulence of field virus. In this study, the efficacy of a recombinant turkey herpesvirus (rHVT) vector vaccine expressing the hemagglutinin gene from a clade 2.2 AI virus (A/Swan/Hungary/4999/2006) was evaluated in turkeys for protection against challenge with A/Whooper Swan/Mongolia/L244/2005 H5N1 HPAI clade 2.2. One-day-old turkeys received a single vaccination and were challenged at 4 wk postvaccination with 2 × 10(6) 50% embryo infectious dose per bird. The results demonstrate that following H5N1 HPAI challenge 96% protection was observed in rHVT-AI vaccinated turkeys. The oral and cloacal swabs taken from challenged birds demonstrated that vaccinated birds had lower incidence and titers of viral shedding compared with sham-vaccinated birds. From respiratory and gastrointestinal tracts, there was a greater than 6 log10 reduction in shedding in vaccinated birds as compared with the controls. This study provides support for the use of a commercially available rHVT-AI vaccine to protect turkeys against H5N1 HPAI. PMID:27309280

  15. Pathobiology and transmission of highly and low pathogenic avian influenza viruses in European quail (Coturnix c. coturnix)

    PubMed Central

    2013-01-01

    European quail (Coturnix c. coturnix) may share with Japanese quail (Coturnix c. japonica) its potential as an intermediate host and reservoir of avian influenza viruses (AIV). To elucidate this question, European quail were experimentally challenged with two highly pathogenic AIV (HPAIV) (H7N1/HP and H5N1/HP) and one low pathogenic AIV (LPAIV) (H7N2/LP). Contact animals were also used to assess the viral transmission among birds. Severe neurological signs and mortality rates of 67% (H7N1/HP) and 92% (H5N1/HP) were observed. Although histopathological findings were present in both HPAIV-infected groups, H5N1/HP-quail displayed a broader viral antigen distribution and extent of microscopic lesions. Neither clinical nor pathological involvement was observed in LPAIV-infected quail. Consistent long-term viral shedding and effective transmission to naive quail was demonstrated for the three studied AIV. Drinking water arose as a possible transmission route and feathers as a potential origin of HPAIV dissemination. The present study demonstrates that European quail may play a major role in AI epidemiology, highlighting the need to further understand its putative role as an intermediate host for avian/mammalian reassortant viruses. PMID:23537387

  16. Highly pathogenic avian influenza H5N1 virus delays apoptotic responses via activation of STAT3.

    PubMed

    Hui, Kenrie P Y; Li, Hung Sing; Cheung, Man Chun; Chan, Renee W Y; Yuen, Kit M; Mok, Chris K P; Nicholls, John M; Peiris, J S Malik; Chan, Michael C W

    2016-01-01

    Highly pathogenic avian influenza (HPAI) H5N1 virus continues to pose pandemic threat, but there is a lack of understanding of its pathogenesis. We compared the apoptotic responses triggered by HPAI H5N1 and low pathogenic H1N1 viruses using physiologically relevant respiratory epithelial cells. We demonstrated that H5N1 viruses delayed apoptosis in primary human bronchial and alveolar epithelial cells (AECs) compared to H1N1 virus. Both caspase-8 and -9 were activated by H5N1 and H1N1 viruses in AECs, while H5N1 differentially up-regulated TRAIL. H5N1-induced apoptosis was reduced by TRAIL receptor silencing. More importantly, STAT3 knock-down increased apoptosis by H5N1 infection suggesting that H5N1 virus delays apoptosis through activation of STAT3. Taken together, we demonstrate that STAT3 is involved in H5N1-delayed apoptosis compared to H1N1. Since delay in apoptosis prolongs the duration of virus replication and production of pro-inflammatory cytokines and TRAIL from H5N1-infected cells, which contribute to orchestrate cytokine storm and tissue damage, our results suggest that STAT3 may play a previously unsuspected role in H5N1 pathogenesis. PMID:27344974

  17. Highly pathogenic avian influenza H5N1 virus delays apoptotic responses via activation of STAT3

    PubMed Central

    Hui, Kenrie P. Y.; Li, Hung Sing; Cheung, Man Chun; Chan, Renee W. Y.; Yuen, Kit M.; Mok, Chris K. P.; Nicholls, John M.; Peiris, J. S. Malik; Chan, Michael C. W.

    2016-01-01

    Highly pathogenic avian influenza (HPAI) H5N1 virus continues to pose pandemic threat, but there is a lack of understanding of its pathogenesis. We compared the apoptotic responses triggered by HPAI H5N1 and low pathogenic H1N1 viruses using physiologically relevant respiratory epithelial cells. We demonstrated that H5N1 viruses delayed apoptosis in primary human bronchial and alveolar epithelial cells (AECs) compared to H1N1 virus. Both caspase-8 and -9 were activated by H5N1 and H1N1 viruses in AECs, while H5N1 differentially up-regulated TRAIL. H5N1-induced apoptosis was reduced by TRAIL receptor silencing. More importantly, STAT3 knock-down increased apoptosis by H5N1 infection suggesting that H5N1 virus delays apoptosis through activation of STAT3. Taken together, we demonstrate that STAT3 is involved in H5N1-delayed apoptosis compared to H1N1. Since delay in apoptosis prolongs the duration of virus replication and production of pro-inflammatory cytokines and TRAIL from H5N1-infected cells, which contribute to orchestrate cytokine storm and tissue damage, our results suggest that STAT3 may play a previously unsuspected role in H5N1 pathogenesis. PMID:27344974

  18. Victims and vectors: highly pathogenic avian influenza H5N1 and the ecology of wild birds

    USGS Publications Warehouse

    Takekawa, John Y.; Prosser, Diann J.; Newman, Scott H.; Muzaffar, Sabir Bin; Hill, Nichola J.; Yan, Baoping; Xiao, Xiangming; Lei, Fumin; Li, Tianxian; Schwarzbach, Steven E.; Howell, Judd A.

    2010-01-01

    The emergence of highly pathogenic avian influenza (HPAI) viruses has raised concerns about the role of wild birds in the spread and persistence of the disease. In 2005, an outbreak of the highly pathogenic subtype H5N1 killed more than 6,000 wild waterbirds at Qinghai Lake, China. Outbreaks have continued to periodically occur in wild birds at Qinghai Lake and elsewhere in Central China and Mongolia. This region has few poultry but is a major migration and breeding area for waterbirds in the Central Asian Flyway, although relatively little is known about migratory movements of different species and connectivity of their wetland habitats. The scientific debate has focused on the role of waterbirds in the epidemiology, maintenance and spread of HPAI H5N1: to what extent are they victims affected by the disease, or vectors that have a role in disease transmission? In this review, we summarise the current knowledge of wild bird involvement in the ecology of HPAI H5N1. Specifically, we present details on: (1) origin of HPAI H5N1; (2) waterbirds as LPAI reservoirs and evolution into HPAI; (3) the role of waterbirds in virus spread and persistence; (4) key biogeographic regions of outbreak; and (5) applying an ecological research perspective to studying AIVs in wild waterbirds and their ecosystems.

  19. A human antibody recognizing a conserved epitope of H5 hemagglutinin broadly neutralizes highly pathogenic avian influenza H5N1 viruses.

    PubMed

    Hu, Hongxing; Voss, Jarrod; Zhang, Guoliang; Buchy, Philippi; Zuo, Teng; Wang, Lulan; Wang, Feng; Zhou, Fan; Wang, Guiqing; Tsai, Cheguo; Calder, Lesley; Gamblin, Steve J; Zhang, Linqi; Deubel, Vincent; Zhou, Boping; Skehel, John J; Zhou, Paul

    2012-03-01

    Influenza A virus infection is a persistent threat to public health worldwide due to its ability to evade immune surveillance through rapid genetic drift and shift. Current vaccines against influenza A virus provide immunity to viral isolates that are similar to vaccine strains. High-affinity neutralizing antibodies against conserved epitopes could provide immunity to diverse influenza virus strains and protection against future pandemic viruses. In this study, by using a highly sensitive H5N1 pseudotype-based neutralization assay to screen human monoclonal antibodies produced by memory B cells from an H5N1-infected individual and molecular cloning techniques, we developed three fully human monoclonal antibodies. Among them, antibody 65C6 exhibited potent neutralization activity against all H5 clades and subclades except for subclade 7.2 and prophylactic and therapeutic efficacy against highly pathogenic avian influenza H5N1 viruses in mice. Studies on hemagglutinin (HA)-antibody complexes by electron microscopy and epitope mapping indicate that antibody 65C6 binds to a conformational epitope comprising amino acid residues at positions 118, 121, 161, 164, and 167 (according to mature H5 numbering) on the tip of the membrane-distal globular domain of HA. Thus, we conclude that antibody 65C6 recognizes a neutralization epitope in the globular head of HA that is conserved among almost all divergent H5N1 influenza stains. PMID:22238297

  20. Surveillance plan for the early detection of H5N1 highly pathogenic avian influenza virus in migratory birds in the United States: surveillance year 2009

    USGS Publications Warehouse

    Brand, Christopher J.

    2009-01-01

    Executive Summary: This Surveillance Plan (Plan) describes plans for conducting surveillance of wild birds in the United States and its Territories and Freely-Associated States to provide for early detection of the introduction of the H5N1 Highly Pathogenic Avian Influenza (HPAI) subtype of the influenza A virus by migratory birds during the 2009 surveillance year, spanning the period of April 1, 2009 - March 31, 2010. The Plan represents a continuation of surveillance efforts begun in 2006 under the Interagency Strategic Plan for the Early Detection of H5N1 Highly Pathogenic Avian Influenza in Wild Migratory Birds (U.S. Department of Agriculture and U.S. Department of the Interior, 2006). The Plan sets forth sampling plans by: region, target species or species groups to be sampled, locations of sampling, sample sizes, and sampling approaches and methods. This Plan will be reviewed annually and modified as appropriate for subsequent surveillance years based on evaluation of information from previous years of surveillance, changing patterns and threats of H5N1 HPAI, and changes in funding availability for avian influenza surveillance. Specific sampling strategies will be developed accordingly within each of six regions, defined here as Alaska, Hawaiian/Pacific Islands, Lower Pacific Flyway (Washington, Oregon, California, Idaho, Nevada, Arizona), Central Flyway, Mississippi Flyway, and Atlantic Flyway.

  1. Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam

    PubMed Central

    Saksena, Sumeet; Fox, Jefferson; Epprecht, Michael; Tran, Chinh C.; Nong, Duong H.; Spencer, James H.; Nguyen, Lam; Finucane, Melissa L.; Tran, Vien D.; Wilcox, Bruce A.

    2015-01-01

    Building on a series of ground breaking reviews that first defined and drew attention to emerging infectious diseases (EID), the ‘convergence model’ was proposed to explain the multifactorial causality of disease emergence. The model broadly hypothesizes disease emergence is driven by the co-incidence of genetic, physical environmental, ecological, and social factors. We developed and tested a model of the emergence of highly pathogenic avian influenza (HPAI) H5N1 based on suspected convergence factors that are mainly associated with land-use change. Building on previous geospatial statistical studies that identified natural and human risk factors associated with urbanization, we added new factors to test whether causal mechanisms and pathogenic landscapes could be more specifically identified. Our findings suggest that urbanization spatially combines risk factors to produce particular types of peri-urban landscapes with significantly higher HPAI H5N1 emergence risk. The work highlights that peri-urban areas of Viet Nam have higher levels of chicken densities, duck and geese flock size diversities, and fraction of land under rice or aquaculture than rural and urban areas. We also found that land-use diversity, a surrogate measure for potential mixing of host populations and other factors that likely influence viral transmission, significantly improves the model’s predictability. Similarly, landscapes where intensive and extensive forms of poultry production overlap were found at greater risk. These results support the convergence hypothesis in general and demonstrate the potential to improve EID prevention and control by combing geospatial monitoring of these factors along with pathogen surveillance programs. PMID:26398118

  2. Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam.

    PubMed

    Saksena, Sumeet; Fox, Jefferson; Epprecht, Michael; Tran, Chinh C; Nong, Duong H; Spencer, James H; Nguyen, Lam; Finucane, Melissa L; Tran, Vien D; Wilcox, Bruce A

    2015-01-01

    Building on a series of ground breaking reviews that first defined and drew attention to emerging infectious diseases (EID), the 'convergence model' was proposed to explain the multifactorial causality of disease emergence. The model broadly hypothesizes disease emergence is driven by the co-incidence of genetic, physical environmental, ecological, and social factors. We developed and tested a model of the emergence of highly pathogenic avian influenza (HPAI) H5N1 based on suspected convergence factors that are mainly associated with land-use change. Building on previous geospatial statistical studies that identified natural and human risk factors associated with urbanization, we added new factors to test whether causal mechanisms and pathogenic landscapes could be more specifically identified. Our findings suggest that urbanization spatially combines risk factors to produce particular types of peri-urban landscapes with significantly higher HPAI H5N1 emergence risk. The work highlights that peri-urban areas of Viet Nam have higher levels of chicken densities, duck and geese flock size diversities, and fraction of land under rice or aquaculture than rural and urban areas. We also found that land-use diversity, a surrogate measure for potential mixing of host populations and other factors that likely influence viral transmission, significantly improves the model's predictability. Similarly, landscapes where intensive and extensive forms of poultry production overlap were found at greater risk. These results support the convergence hypothesis in general and demonstrate the potential to improve EID prevention and control by combing geospatial monitoring of these factors along with pathogen surveillance programs. PMID:26398118

  3. Determinants of Knowledge and Biosecurity Preventive Behaviors for Highly Pathogenic Avian Influenza Risk Among Chinese Poultry Farmers.

    PubMed

    Cui, Bin; Liu, Zong Ping

    2016-06-01

    Biosecurity measures are the first line of defense against highly pathogenic avian influenza (HPAI) on farms. It is generally recognized that an individual's behavior can be influenced by the knowledge they possess. However, empirical study has not reported an association between poultry producers' awareness of HPAI symptoms and their actual biosecurity actions. The aim of this study is to classify knowledge items of HPAI by exploratory factor analysis (EFA) and to examine the determinants of different types of knowledge and the effect of different types of knowledge on biosecurity preventive behaviors (BPBs). The survey (n = 297) was conducted using a questionnaire to measure the level of awareness of items related to HPAI and the actual adoption of BPBs among poultry farmers in the Chinese province of Jiangsu. The EFA revealed three main types of knowledge, which were categorized as avian influenza (AI) epidemic characteristics, primary biosecurity preventive knowledge (basic biosecurity preventive knowledge against AI), and essential biosecurity preventive knowledge (crucial biosecurity preventive knowledge against infection of AI). Multivariate regression showed that only poultry farmers' awareness of essential biosecurity preventive knowledge was positively associated with their actual BPBs. Additionally, educational attainment, number of years of experience raising poultry, farming operation size, and training were associated both with BPB and most of the knowledge factors or knowledge items. Training of existing poultry farmers is probably a feasible scheme; furthermore, the training should focus on the essential biosecurity preventive knowledge. On the other hand, policy initiatives to encourage large-scale poultry farming while discouraging small-scale backyard poultry husbandry would be an effective method of improving the management standards of rural poultry farming. PMID:27309291

  4. U.S. Geological Survey science strategy for highly pathogenic avian influenza in wildlife and the environment (2016–2020)

    USGS Publications Warehouse

    Harris, M. Camille; Pearce, John M.; Prosser, Diann J.; White, C. LeAnn; Miles, A. Keith; Sleeman, Jonathan M.; Brand, Christopher J.; Cronin, James P.; De La Cruz, Susan; Densmore, Christine L.; Doyle, Thomas W.; Dusek, Robert J.; Fleskes, Joseph P.; Flint, Paul L.; Guala, Gerald F.; Hall, Jeffrey S.; Hubbard, Laura E.; Hunt, Randall J.; Ip, Hon S.; Katz, Rachel A.; Laurent, Kevin W.; Miller, Mark P.; Munn, Mark D.; Ramey, Andy M.; Richards, Kevin D.; Russell, Robin E.; Stokdyk, Joel P.; Takekawa, John Y.; Walsh, Daniel P.

    2016-01-01

    IntroductionThrough the Science Strategy for Highly Pathogenic Avian Influenza (HPAI) in Wildlife and the Environment, the USGS will assess avian influenza (AI) dynamics in an ecological context to inform decisions made by resource managers and policymakers from the local to national level. Through collection of unbiased scientific information on the ecology of AI viruses and wildlife hosts in a changing world, the U.S. Geological Survey (USGS) will enhance the development of AI forecasting tools and ensure this information is integrated with a quality decision process for managing HPAI.The overall goal of this USGS Science Strategy for HPAI in Wildlife and the Environment goes beyond document­ing the occurrence and distribution of AI viruses in wild birds. The USGS aims to understand the epidemiological processes and environmental factors that influence HPAI distribution and describe the mechanisms of transmission between wild birds and poultry. USGS scientists developed a conceptual model describing the process linking HPAI dispersal in wild waterfowl to the outbreaks in poul­try. This strategy focuses on five long-term science goals, which include:Science Goal 1—Augment the National HPAI Surveillance Plan;Science Goal 2—Determine mechanisms of HPAI disease spread in wildlife and the environment;Science Goal 3—Characterize HPAI viruses circulating in wildlife;Science Goal 4—Understand implications of avian ecol­ogy on HPAI spread; andScience Goal 5—Develop HPAI forecasting and decision-making tools.These goals will help define and describe the processes outlined in the conceptual model with the ultimate goal of facilitating biosecurity and minimizing transfer of diseases across the wildlife-poultry interface. The first four science goals are focused on scientific discovery and the fifth goal is application-based. Decision analyses in the fifth goal will guide prioritization of proposed actions in the first four goals.

  5. Evolutionary dynamics of highly pathogenic avian influenza A/H5N1 HA clades and vaccine implementation in Vietnam

    PubMed Central

    Nguyen, Nga Thi Bich

    2014-01-01

    Based on hemagglutinin (HA) and neuraminidase (NA), influenza A virus is divided into 18 different HA (H1 to H18) and 11 NA types (N1 to N11), opening the possibility for reassortment between the HA and NA genes to generate new HxNy subtypes (where x could be any HA and y is any NA, possibly). In recent four years, since 2010, highly pathogenic avian influenza (HPAI) viruses of H5N1 subtype (HPAI A/H5N1) have become highly enzootic and dynamically evolved to form multiple H5 HA clades, particularly in China, Vietnam, Indonesia, Egypt, Cambodia, and Bangladesh. So far, after more than 10 years emerged in Vietnam (since late 2003), HPAI A/H5N1 is still posing a potential risk of causing outbreaks in poultry, with high frequency of annual endemics. Intragenic variation (referred to as antigenic drift) in HA (e.g., H5) has given rise to form numerous clades, typically marking the major timelines of the evolutionary status and vaccine application in each period. The dominance of genetically and antigenically diversified clade 2.3.2.1 (of subgroups a, b, c), clade 1.1 (1.1.1/1.1.2) and re-emergence of clade 7.1/7.2 at present, has urged Vietnam to the need for dynamically applied antigenicity-matching vaccines, i.e., the plan of importing Re-6 vaccine for use in 2014, in parallel use of Re-1/Re-5 since 2006. In this review, we summarize evolutionary features of HPAI A/H5N1 viruses and clade formation during recent 10 years (2004-2014). Dynamic of vaccine implementation in Vienam is also remarked. PMID:25003084

  6. Intranasal H5N1 vaccines, adjuvanted with chitosan derivatives, protect ferrets against highly pathogenic influenza intranasal and intratracheal challenge.

    PubMed

    Mann, Alex J; Noulin, Nicolas; Catchpole, Andrew; Stittelaar, Koert J; de Waal, Leon; Veldhuis Kroeze, Edwin J B; Hinchcliffe, Michael; Smith, Alan; Montomoli, Emanuele; Piccirella, Simona; Osterhaus, Albert D M E; Knight, Alastair; Oxford, John S; Lapini, Giulia; Cox, Rebecca; Lambkin-Williams, Rob

    2014-01-01

    We investigated the protective efficacy of two intranasal chitosan (CSN and TM-CSN) adjuvanted H5N1 Influenza vaccines against highly pathogenic avian Influenza (HPAI) intratracheal and intranasal challenge in a ferret model. Six groups of 6 ferrets were intranasally vaccinated twice, 21 days apart, with either placebo, antigen alone, CSN adjuvanted antigen, or TM-CSN adjuvanted antigen. Homologous and intra-subtypic antibody cross-reacting responses were assessed. Ferrets were inoculated intratracheally (all treatments) or intranasally (CSN adjuvanted and placebo treatments only) with clade 1 HPAI A/Vietnam/1194/2004 (H5N1) virus 28 days after the second vaccination and subsequently monitored for morbidity and mortality outcomes. Clinical signs were assessed and nasal as well as throat swabs were taken daily for virology. Samples of lung tissue, nasal turbinates, brain, and olfactory bulb were analysed for the presence of virus and examined for histolopathological findings. In contrast to animals vaccinated with antigen alone, the CSN and TM-CSN adjuvanted vaccines induced high levels of antibodies, protected ferrets from death, reduced viral replication and abrogated disease after intratracheal challenge, and in the case of CSN after intranasal challenge. In particular, the TM-CSN adjuvanted vaccine was highly effective at eliciting protective immunity from intratracheal challenge; serologically, protective titres were demonstrable after one vaccination. The 2-dose schedule with TM-CSN vaccine also induced cross-reactive antibodies to clade 2.1 and 2.2 H5N1 viruses. Furthermore ferrets immunised with TM-CSN had no detectable virus in the respiratory tract or brain, whereas there were signs of virus in the throat and lungs, albeit at significantly reduced levels, in CSN vaccinated animals. This study demonstrated for the first time that CSN and in particular TM-CSN adjuvanted intranasal vaccines have the potential to protect against significant mortality and

  7. Analysis of spatial distribution and transmission characters for highly pathogenic avian influenza in Chinese mainland in 2004

    NASA Astrophysics Data System (ADS)

    Liu, Y. L.; Wei, C. J.; Yan, L.; Chi, T. H.; Wu, X. B.; Xiao, C. S.

    2006-03-01

    After the outbreak of highly pathogenic Avian Influenza (HPAI) in South Korea in the end of year 2003, estimates of the impact of HPAI in affected countries vary greatly, the total direct losses are about 3 billion US dollars, and it caused 15 million birds and poultry flocks death. It is significant to understand the spatial distribution and transmission characters of HPAI for its prevention and control. According to 50 outbreak cases for HPAI in Chinese mainland during 2004, this paper introduces the approach of spatial distribution and transmission characters for HPAI and its results. Its approach is based on remote sensing and GIS techniques. Its supporting data set involves normalized difference vegetation index (NDVI) and land surface temperature (Ts) derived from a time-series of remote sensing data of 1 kilometer-resolution NOAA/AVHRR, birds' migration routes, topology geographic map, lake and wetland maps, and meteorological observation data. In order to analyze synthetically using these data, a supporting platform for analysis Avian Influenza epidemic situation (SPAS/AI) was developed. Supporting by SPAS/AI, the integrated information from multi-sources can be easily used to the analysis of the spatial distribution and transmission character of HPAI. The results show that the range of spatial distribution and transmission of HPAI in China during 2004 connected to environment factors NDVI, Ts and the distributions of lake and wetland, and especially to bird migration routes. To some extent, the results provide some suggestions for the macro-decision making for the prevention and control of HPAI in the areas of potential risk and reoccurrence.

  8. Gas-permeable ethylene bags for the small scale cultivation of highly pathogenic avian influenza H5N1 and other viruses in embryonated chicken eggs

    PubMed Central

    2010-01-01

    Background Embryonated chicken eggs (ECE) are sometimes used for the primary isolation or passage of influenza viruses, other viruses, and certain bacteria. For small-scale experiments with pathogens that must be studied in biosafety level three (BSL3) facilities, inoculated ECE are sometimes manipulated and maintained in small egg incubators within a biosafety cabinet (BSC). To simplify the clean up and decontamination of an egg incubator in case of egg breakage, we explored whether ethylene breather bags could be used to encase ECE inoculated with pathogens. This concept was tested by determining embryo survival and examining virus yields in bagged ECE. Results Virus yields acceptable for many applications were attained when influenza-, alpha-, flavi-, canine distemper-, and mousepox viruses were propagated in ECE sealed within ethylene breather bags. Conclusions For many small-scale applications, ethylene breather bags can be used to encase ECE inoculated with various viruses. PMID:20109234

  9. Testing of human specimens for the presence of highly pathogenic zoonotic avian influenza virus A(H5N1) in Poland in 2006-2008 - justified or unnecessary steps?

    PubMed

    Romanowska, Magdalena; Nowak, Iwona; Brydak, Lidia; Wojtyla, Andrzej

    2009-01-01

    Since 1997, human infections with highly pathogenic zoonotic avian influenza viruses have shown that the risk of influenza pandemic is significant. In Europe, infections caused by the highly pathogenic avian influenza A(H7N7) virus were confirmed in the human population in 2003 in the Netherlands. Moreover, outbreaks of A(H5N1) infections were observed in wild and farm birds in different European regions, including Poland in 2006-2008. This study presents 16 patients in Poland from whom clinical specimens were collected and tested for A(H5N1) highly pathogenic avian influenza. This article shows the results of laboratory tests and discusses the legitimacy of the collection and testing of the specimens. All patients were negative for A(H5N1) infection. Nevertheless, only two patients met clinical and epidemiological criteria from the avian influenza case definition. The conclusion is that there is still a strong necessity for increasing the awareness of medical and laboratory staff, as well as the awareness of some occupational groups about human infections with avian influenza viruses, including the importance of seasonal influenza vaccination. It should also be emphasized that in the case of patients suspected of being infected with avian influenza, the information about clinical symptoms is insufficient and must be accompanied by a wide epidemiological investigation. PMID:20047257

  10. Assessment of the Internal Genes of Influenza A (H7N9) Virus Contributing to High Pathogenicity in Mice

    PubMed Central

    Bi, Yuhai; Xie, Qing; Zhang, Shuang; Li, Yun; Xiao, Haixia; Jin, Tao; Zheng, Weinan; Li, Jing; Jia, Xiaojuan; Sun, Lei; Liu, Jinhua; Qin, Chuan

    2014-01-01

    ABSTRACT The recently identified H7N9 influenza A virus has caused severe economic losses and worldwide public concern. Genetic analysis indicates that its six internal genes all originated from H9N2 viruses. However, the H7N9 virus is more highly pathogenic in humans than H9N2, which suggests that the internal genes of H7N9 have mutated. To analyze which H7N9 virus internal genes contribute to its high pathogenicity, a series of reassortants was generated by reverse genetics, with each virus containing a single internal gene of the typical A/Anhui/1/2013 (H7N9) (AH-H7N9) virus in the genetic background of the A/chicken/Shandong/lx1023/2007 (H9N2) virus. The replication ability, polymerase activity, and pathogenicity of these viruses were then evaluated in vitro and in vivo. These recombinants displayed high genetic compatibility, and the H7N9-derived PB2, M, and NP genes were identified as the virulence genes for the reassortants in mice. Further investigation confirmed that the PB2 K627 residue is critical for the high pathogenicity of the H7N9 virus and the reassortant containing the H7N9-derived PB2 segment (H9N2-AH/PB2). Notably, the H7N9-derived PB2 gene displayed greater compatibility with the H9N2 genome than that of H7N9, endowing the H9N2-AH/PB2 reassortant with greater viability and virulence than the parental H7N9 virus. In addition, the H7N9 virus, with the exception of the H9N2 reassortants, could effectively replicate in human A549 cells. Our results indicate that PB2, M, and NP are the key virulence genes, together with the surface hemagglutinin (HA) and neuraminidase (NA) proteins, contributing to the high infectivity of the H7N9 virus in humans. IMPORTANCE To date, the novel H7N9 influenza A virus has caused 437 human infections, with approximately 30% mortality. Previous work has primarily focused on the two viral surface proteins, HA and NA, but the contribution of the six internal genes to the high pathogenicity of H7N9 has not been

  11. Major Histocompatibility Complex and Background Genes in Chickens Influence Susceptibility to High Pathogenicity Avian Influenza Virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The chicken’s major histocompatibility complex (MHC) haplotype has profound influence on the resistance or susceptibility to certain pathogens such as B21 MHC haplotype confers resistance to Marek’s disease (MD). However, non-MHC genes are also important in disease resistance. For example, both line...

  12. Evidence for common ancestry among viruses isolated from wild birds in Beringia and highly pathogenic intercontinental reassortant H5N1 and H5N2 influenza A viruses.

    PubMed

    Ramey, Andrew M; Reeves, Andrew B; TeSlaa, Joshua L; Nashold, Sean; Donnelly, Tyrone; Bahl, Justin; Hall, Jeffrey S

    2016-06-01

    Highly pathogenic clade 2.3.4.4 H5N8, H5N2, and H5N1 influenza A viruses were first detected in wild, captive, and domestic birds in North America in November-December 2014. In this study, we used wild waterbird samples collected in Alaska prior to the initial detection of clade 2.3.4.4 H5 influenza A viruses in North America to assess the evidence for: (1) dispersal of highly pathogenic influenza A viruses from East Asia to North America by migratory birds via Alaska and (2) ancestral origins of clade 2.3.4.4 H5 reassortant viruses in Beringia. Although we did not detect highly pathogenic influenza A viruses in our sample collection from western Alaska, we did identify viruses that contained gene segments sharing recent common ancestry with intercontinental reassortant H5N2 and H5N1 viruses. Results of phylogenetic analyses and estimates for times of most recent common ancestry support migratory birds sampled in Beringia as maintaining viral diversity closely related to novel highly pathogenic influenza A virus genotypes detected in North America. Although our results do not elucidate the route by which highly pathogenic influenza A viruses were introduced into North America, genetic evidence is consistent with the hypothesized trans-Beringian route of introduction via migratory birds. PMID:26944444

  13. Evidence for common ancestry among viruses isolated from wild birds in Beringia and highly pathogenic intercontinental reassortant H5N1 and H5N2 influenza A viruses

    USGS Publications Warehouse

    Ramey, Andy M.; Reeves, Andrew; Teslaa, Joshua L.; Nashold, Sean W.; Donnelly, Tyrone F.; Bahl, Justin; Hall, Jeffrey S.

    2016-01-01

    Highly pathogenic clade 2.3.4.4 H5N8, H5N2, and H5N1 influenza A viruses were first detected in wild, captive, and domestic birds in North America in November–December 2014. In this study, we used wild waterbird samples collected in Alaska prior to the initial detection of clade 2.3.4.4 H5 influenza A viruses in North America to assess the evidence for: (1) dispersal of highly pathogenic influenza A viruses from East Asia to North America by migratory birds via Alaska and (2) ancestral origins of clade 2.3.4.4 H5 reassortant viruses in Beringia. Although we did not detect highly pathogenic influenza A viruses in our sample collection from western Alaska, we did identify viruses that contained gene segments sharing recent common ancestry with intercontinental reassortant H5N2 and H5N1 viruses. Results of phylogenetic analyses and estimates for times of most recent common ancestry support migratory birds sampled in Beringia as maintaining viral diversity closely related to novel highly pathogenic influenza A virus genotypes detected in North America. Although our results do not elucidate the route by which highly pathogenic influenza A viruses were introduced into North America, genetic evidence is consistent with the hypothesized trans-Beringian route of introduction via migratory birds.

  14. Cutaneous Co-infected Cytomegalovirus and Herpes Simplex Virus Perigenital Ulcers in Human Immunodeficiency Virus Patients.

    PubMed

    Schoenfeld, Jason; Cannon, Sarah; Cam, Kristin; Keller, Matthew

    2013-10-01

    There is uncertainty regarding the pathogenic nature of cytomegalovirus in cutaneous lesions co-infected with herpes simplex virus. It is widely believed that herpes simplex virus is the main pathogenic factor in such lesions and that cytomegalovirus plays little if any role. There are, however, isolated case reports that describe cytomegalovirus as an important driving pathogen in such lesions. The authors present two human immunodeficiency virus patients who have cytomegalovirus and herpes simplex virus co-infected perigenital ulcers, one of whom improved on valacyclovir, while the other, who was already on valacyclovir for chronic herpes simplex virus suppression, showed no improvement with a single dose of cidofovir. He only showed rapid improvement when treated with valganciclovir. The latter patient underscores the viewpoint that at least in some cases, cytomegalovirus may be an important driving force behind the formation of such lesions. The authors therefore recommend that clinicians be aware of the possible pathogenic role of cytomegalovirus in these ulcers, and, in nonhealing ulcers, use anti-cytomegalovirus agents to prevent the onset of systemic disease. These results warrant further study of the pathogenesis of cytomegalovirus in co-infected herpes simplex virus ulcers. PMID:24155993

  15. X-ray structure of NS1 from a highly pathogenic H5N1 influenza virus

    SciTech Connect

    Bornholdt, Zachary A.; Prasad, B.V. Venkataram

    2009-04-08

    The recent emergence of highly pathogenic avian (H5N1) influenza viruses, their epizootic and panzootic nature, and their association with lethal human infections have raised significant global health concerns. Several studies have underlined the importance of non-structural protein NS1 in the increased pathogenicity and virulence of these strains. NS1, which consists of two domains - a double-stranded RNA (dsRNA) binding domain and the effector domain, separated through a linker - is an antagonist of antiviral type-I interferon response in the host. Here we report the X-ray structure of the full-length NS1 from an H5N1 strain (A/Vietnam/1203/2004) that was associated with 60% of human deaths in an outbreak in Vietnam. Compared to the individually determined structures of the RNA binding domain and the effector domain from non-H5N1 strains, the RNA binding domain within H5N1 NS1 exhibits modest structural changes, while the H5N1 effector domain shows significant alteration, particularly in the dimeric interface. Although both domains in the full-length NS1 individually participate in dimeric interactions, an unexpected finding is that these interactions result in the formation of a chain of NS1 molecules instead of distinct dimeric units. Three such chains in the crystal interact with one another extensively to form a tubular organization of similar dimensions to that observed in the cryo-electron microscopy images of NS1 in the presence of dsRNA. The tubular oligomeric organization of NS1, in which residues implicated in dsRNA binding face a 20-{angstrom}-wide central tunnel, provides a plausible mechanism for how NS1 sequesters varying lengths of dsRNA, to counter cellular antiviral dsRNA response pathways, while simultaneously interacting with other cellular ligands during an infection.

  16. Comprehensive analysis of antibody recognition in convalescent humans from highly pathogenic avian influenza H5N1 infection

    PubMed Central

    Zuo, Teng; Sun, Jianfeng; Wang, Guiqin; Jiang, Liwei; Zuo, Yanan; Li, Danyang; Shi, Xuanling; Liu, Xi; Fan, Shilong; Ren, Huanhuan; Hu, Hongxing; Sun, Lina; Zhou, Boping; Liang, Mifang; Zhou, Paul; Wang, Xinquan; Zhang, Linqi

    2015-01-01

    Understanding the mechanism of protective antibody recognition against highly pathogenic avian influenza A virus H5N1 in humans is critical for the development of effective therapies and vaccines. Here we report the crystal structure of three H5-specific human monoclonal antibodies bound to the globular head of hemagglutinin (HA) with distinct epitope specificities, neutralization potencies and breadth. A structural and functional analysis of these epitopes combined with those reported elsewhere identifies four major vulnerable sites on the globular head of H5N1 HA. Chimeric and vulnerable site-specific mutant pseudoviruses are generated to delineate broad neutralization specificities of convalescent sera from two individuals who recovered from the infection with H5N1 virus. Our results show that the four vulnerable sites on the globular head rather than the stem region are the major neutralizing targets, suggesting that during natural H5N1 infection neutralizing antibodies against the globular head work in concert to provide protective antibody-mediated immunity. PMID:26635249

  17. Prevalence and diversity of low pathogenicity avian influenza viruses in wild birds in Guatemala, 2010-2013

    PubMed Central

    Gonzalez-Reiche, Ana S.; Müller, Maria L.; Ortiz, Lucía; Cordón-Rosales, Celia; Perez, Daniel R.

    2016-01-01

    Summary Waterfowl species are known to harbor the greatest diversity of low pathogenicity influenza A virus (LPAIV) subtypes and are recognized as their main natural reservoir. In Guatemala there is evidence of circulation of LPAIV in wild ducks, however the bird species contributing to viral diversity during the winter migration in Central America are unknown. In this study, samples obtained from 1,250 hunter-killed birds from 22 different species were collected on the Pacific coast of Guatemala during three winter migration seasons between 2010 and 2013. Prevalence of LPAIV detected by real-time reverse-transcriptase polymerase chain reaction was 38.2%, 23.5% and 24.7% in the 2010-11, 2011-12, and 2012-13 seasons respectively. The highest virus prevalence was detected in the northern shoveler (Anas clypeata), followed by the blue-winged teal (Anas discors). The majority of positive samples and viral isolates were obtained from the blue-winged teal. Analysis of LPAIV prevalence over time in this species indicated a decreasing trend in monthly prevalence within a migration season. Sixty-eight viruses were isolated and 9 HA and 7 NA subtypes were identified in 19 subtype combinations. In 2012-13, the most prevalent subtype was H14, a subtype identified for the first time in the western hemisphere in 2010. The results from this study represent the most detailed description available to date of LPAIV circulation in Central America. PMID:27309080

  18. Spatio-Temporal Data Comparisons for Global Highly Pathogenic Avian Influenza (HPAI) H5N1 Outbreaks

    PubMed Central

    Chen, Dongmei; Chen, Yue; Wang, Lei; Zhao, Fei; Yao, Baodong

    2010-01-01

    Highly pathogenic avian influenza subtype H5N1 is a zoonotic disease and control of the disease is one of the highest priority in global health. Disease surveillance systems are valuable data sources for various researches and management projects, but the data quality has not been paid much attention in previous studies. Based on data from two commonly used databases (Office International des Epizooties (OIE) and Food and Agriculture Organization of the United Nations (FAO)) of global HPAI H5N1 outbreaks during the period of 2003–2009, we examined and compared their patterns of temporal, spatial and spatio-temporal distributions for the first time. OIE and FAO data showed similar trends in temporal and spatial distributions if they were considered separately. However, more advanced approaches detected a significant difference in joint spatio-temporal distribution. Because of incompleteness for both OIE and FAO data, an integrated dataset would provide a more complete picture of global HPAI H5N1 outbreaks. We also displayed a mismatching profile of global HPAI H5N1 outbreaks and found that the degree of mismatching was related to the epidemic severity. The ideas and approaches used here to assess spatio-temporal data on the same disease from different sources are useful for other similar studies. PMID:21187964

  19. Replication and Adaptive Mutations of Low Pathogenic Avian Influenza Viruses in Tracheal Organ Cultures of Different Avian Species

    PubMed Central

    Petersen, Henning; Matrosovich, Mikhail; Pleschka, Stephan; Rautenschlein, Silke

    2012-01-01

    Transmission of avian influenza viruses (AIV) between different avian species may require genome mutations that allow efficient virus replication in a new species and could increase virulence. To study the role of domestic poultry in the evolution of AIV we compared replication of low pathogenic (LP) AIV of subtypes H9N2, H7N7 and H6N8 in tracheal organ cultures (TOC) and primary embryo fibroblast cultures of chicken, turkey, Pekin duck and homing pigeon. Virus strain-dependent and avian species-related differences between LPAIV were observed in growth kinetics and induction of ciliostasis in TOC. In particular, our data demonstrate high susceptibility to LPAIV of turkey TOC contrasted with low susceptibility of homing pigeon TOC. Serial virus passages in the cells of heterologous host species resulted in adaptive mutations in the AIV genome, especially in the receptor-binding site and protease cleavage site of the hemagglutinin. Our data highlight differences in susceptibility of different birds to AIV viruses and emphasizes potential role of poultry in the emergence of new virus variants. PMID:22912693

  20. Microevolution of Highly Pathogenic Avian Influenza A(H5N1) Viruses Isolated from Humans, Egypt, 2007–2011

    PubMed Central

    Younan, Mary; Poh, Mee Kian; Elassal, Emad; Davis, Todd; Rivailler, Pierre; Balish, Amanda L.; Simpson, Natosha; Jones, Joyce; Deyde, Varough; Loughlin, Rosette; Perry, Ije; Gubareva, Larisa; ElBadry, Maha A.; Truelove, Shaun; Gaynor, Anne M.; Mohareb, Emad; Amin, Magdy; Cornelius, Claire; Pimentel, Guillermo; Earhart, Kenneth; Naguib, Amel; Abdelghani, Ahmed S.; Refaey, Samir; Klimov, Alexander I.; Kandeel, Amr

    2013-01-01

    We analyzed highly pathogenic avian influenza A(H5N1) viruses isolated from humans infected in Egypt during 2007–2011. All analyzed viruses evolved from the lineage of subtype H5N1 viruses introduced into Egypt in 2006; we found minimal evidence of reassortment and no exotic introductions. The hemagglutinin genes of the viruses from 2011 formed a monophyletic group within clade 2.2.1 that also included human viruses from 2009 and 2010 and contemporary viruses from poultry; this finding is consistent with zoonotic transmission. Although molecular markers suggestive of decreased susceptibility to antiviral drugs were detected sporadically in the neuraminidase and matrix 2 proteins, functional neuraminidase inhibition assays did not identify resistant viruses. No other mutations suggesting a change in the threat to public health were detected in the viral proteomes. However, a comparison of representative subtype H5N1 viruses from 2011 with older subtype H5N1 viruses from Egypt revealed substantial antigenic drift. PMID:23260983

  1. Assessing the risk of highly pathogenic avian influenza H5N1 transmission through poultry movements in Bali, Indonesia.

    PubMed

    Roche, Sharon E; Cogger, Naomi; Garner, M Graeme; Putra, Anak Agung Gde; Toribio, Jenny-Ann L M L

    2014-03-01

    Indonesia continues to report the highest number of human and poultry cases of highly pathogenic avian influenza H5N1. The disease is considered to be endemic on the island of Bali. Live bird markets are integral in the poultry supply chain on Bali and are important, nutritionally and culturally, for the rural and urban human populations. Due to the lack of biosecurity practiced along the supply chain from producer to live bird markets, there is a need to understand the risks associated with the spread of H5N1 through live bird movements for effective control. Resources to control H5N1 in Indonesia are very limited and cost effective strategies are needed. We assessed the probability a live bird market is infected through live poultry movements and assessed the effects of implementing two simple and low cost control measures on this risk. Results suggest there is a high risk a live bird market is infected (0.78), and risk mitigation strategies such as detecting and removing infected poultry from markets reduce this risk somewhat (range 0.67-0.76). The study demonstrates the key role live poultry movements play in transmitting H5N1 and the need to implement a variety of control measures to reduce disease spread. PMID:24439035

  2. Prevalence and Diversity of Low Pathogenicity Avian Influenza Viruses in Wild Birds in Guatemala, 2010-2013.

    PubMed

    Gonzalez-Reiche, Ana S; Müller, Maria L; Ortiz, Lucía; Cordón-Rosales, Celia; Perez, Daniel R

    2016-05-01

    Waterfowl species are known to harbor the greatest diversity of low pathogenicity influenza A virus (LPAIV) subtypes and are recognized as their main natural reservoir. In Guatemala there is evidence of circulation of LPAIV in wild ducks; however, the bird species contributing to viral diversity during the winter migration in Central America are unknown. In this study, samples obtained from 1250 hunter-killed birds from 22 different species were collected on the Pacific coast of Guatemala during three winter migration seasons between 2010 and 2013. Prevalence of LPAIV detected by real-time reverse-transcriptase polymerase chain reaction was 38.2%, 23.5%, and 24.7% in the 2010-11, 2011-12, and 2012-13 seasons, respectively. The highest virus prevalence was detected in the northern shoveler (Anas clypeata), followed by the blue-winged teal (Anas discors). The majority of positive samples and viral isolates were obtained from the blue-winged teal. Analysis of LPAIV prevalence over time in this species indicated a decreasing trend in monthly prevalence within a migration season. Sixty-eight viruses were isolated, and nine HA and seven NA subtypes were identified in 19 subtype combinations. In 2012-13 the most prevalent subtype was H14, a subtype identified for the first time in the Western Hemisphere in 2010. The results from this study represent the most detailed description available to date of LPAIV circulation in Central America. PMID:27309080

  3. No evidence of infection or exposure to Highly Pathogenic Avian Influenzas in peridomestic wildlife on an affected poultry facility

    USGS Publications Warehouse

    Grear, Daniel; Dusek, Robert J.; Walsh, Daniel P.; Hall, Jeffrey S.

    2016-01-01

    We evaluated the potential transmission of avian influenza viruses (AIV) in wildlife species in three settings in association with an outbreak at a poultry facility: 1) small birds and small mammals on a poultry facility that was affected with highly pathogenic AIV (HPAIV) in April 2015; 2) small birds and small mammals on a nearby poultry facility that was unaffected by HPAIV; and 3) small birds, small mammals, and waterfowl in a nearby natural area. We live-captured small birds and small mammals and collected samples from hunter-harvested waterfowl to test for active viral shedding and evidence of exposure (serum antibody) to AIV and the H5N2 HPAIV that affected the poultry facility. We detected no evidence of shedding or specific antibody to AIV in small mammals and small birds 5 mo after depopulation of the poultry. We detected viral shedding and exposure to AIV in waterfowl and estimated approximately 15% viral shedding and 60% antibody prevalence. In waterfowl, we did not detect shedding or exposure to the HPAIV that affected the poultry facility. We also conducted camera trapping around poultry carcass depopulation composting barns and found regular visitation by four species of medium-sized mammals. We provide preliminary data suggesting that peridomestic wildlife were not an important factor in the transmission of AIV during the poultry outbreak, nor did small birds and mammals in natural wetland settings show wide evidence of AIV shedding or exposure, despite the opportunity for exposure.

  4. Comprehensive analysis of antibody recognition in convalescent humans from highly pathogenic avian influenza H5N1 infection.

    PubMed

    Zuo, Teng; Sun, Jianfeng; Wang, Guiqin; Jiang, Liwei; Zuo, Yanan; Li, Danyang; Shi, Xuanling; Liu, Xi; Fan, Shilong; Ren, Huanhuan; Hu, Hongxing; Sun, Lina; Zhou, Boping; Liang, Mifang; Zhou, Paul; Wang, Xinquan; Zhang, Linqi

    2015-01-01

    Understanding the mechanism of protective antibody recognition against highly pathogenic avian influenza A virus H5N1 in humans is critical for the development of effective therapies and vaccines. Here we report the crystal structure of three H5-specific human monoclonal antibodies bound to the globular head of hemagglutinin (HA) with distinct epitope specificities, neutralization potencies and breadth. A structural and functional analysis of these epitopes combined with those reported elsewhere identifies four major vulnerable sites on the globular head of H5N1 HA. Chimeric and vulnerable site-specific mutant pseudoviruses are generated to delineate broad neutralization specificities of convalescent sera from two individuals who recovered from the infection with H5N1 virus. Our results show that the four vulnerable sites on the globular head rather than the stem region are the major neutralizing targets, suggesting that during natural H5N1 infection neutralizing antibodies against the globular head work in concert to provide protective antibody-mediated immunity. PMID:26635249

  5. Annual survival of ruddy turnstones is not affected by natural infection with low pathogenicity avian influenza viruses.

    PubMed

    Maxted, Angela M; Porter, Ronald R; Luttrell, M Page; Goekjian, Virginia H; Dey, Amanda D; Kalasz, Kevin S; Niles, Lawrence J; Stallknecht, David E

    2012-09-01

    The population of ruddy turnstones (Arenaria interpres morinella) that migrates through Delaware Bay has undergone severe declines in recent years, attributable to reduced availability of horseshoe crab (Limulus polyphemus) eggs at this critical spring migration stopover site. Concurrently, this population has experienced annual low pathogenicity avian influenza virus (AIV) epidemics at this same site. Using a prospective cohort study design with birds individually flagged during May-June 2006-2008, we evaluated resighting rates (a proxy for annual survival) between AIV-infected and uninfected birds at 1 yr after capture, testing, and measurement. Overall resighting rate was 46%, which varied by year and increased with relative mass of the bird when captured. Resighting rates were not different between AIV-infected and uninfected birds in any period. In multivariate analyses, infection status was also unrelated to resighting rate after controlling for year, day, state, sex, body size, mass index, or whether the bird was blood-sampled. Thus, apparent annual survival in ruddy turnstones was not reduced by AIV infection at this migratory stopover. However, it is unknown whether intestinal AIV infection might cause subtle reductions in weight gain which could negatively influence reproduction. PMID:23050475

  6. Susceptibility of North American Ducks and Gulls to H5N1 Highly Pathogenic Avian Influenza Viruses

    PubMed Central

    Stallknecht, David E.; Beck, Joan R.; Suarez, David L.; Swayne, David E.

    2006-01-01

    Since 2002, H5N1 highly pathogenic avian influenza (HPAI) viruses have been associated with deaths in numerous wild avian species throughout Eurasia. We assessed the clinical response and extent and duration of viral shedding in 5 species of North American ducks and laughing gulls (Larus atricilla) after intranasal challenge with 2 Asian H5N1 HPAI viruses. Birds were challenged at ≈10 to 16 weeks of age, consistent with temporal peaks in virus prevalence and fall migration. All species were infected, but only wood ducks (Aix sponsa) and laughing gulls exhibited illness or died. Viral titers were higher in oropharyngeal swabs than in cloacal swabs. Duration of viral shedding (1–10 days) increased with severity of clinical disease. Both the hemagglutination-inhibition (HI) and agar gel precipitin (AGP) tests were able to detect postinoculation antibodies in surviving wood ducks and laughing gulls; the HI test was more sensitive than the AGP in the remaining 4 species PMID:17283615

  7. Pathogenic characteristics of a novel triple-reasserted H1N2 swine influenza virus.

    PubMed

    Liu, Huili; Tao, Jie; Zhang, Pengchao; Yin, Xiuchen; Ha, Zhuo; Zhang, Chunling

    2016-07-01

    A novel triple reasserted H1N2 virus A/swine/Shanghai/1/2007 (SH07) was isolated from nasal swabs of weaned pig showing clinical symptoms of coughing and sneezing. To explore the virus characteristics, mice, chickens and pigs were selected for pathogenicity study. Pigs inoculated intranasally with 10(6) TCID50 SH07 showed clinical symptoms with coughing and sneezing, but no death. The virus nuclear acid was detected in many tissues using real-time PCR, which was mainly distributed in respiratory system particularly in the lungs. The virus was low-pathogenic to chickens with 10(6) TCID50 dose inoculation either via intramuscular or intranasal routes. However virus nuclear acid detection and virus isolation confirmed that the virus can also be found in nasal and rectum. When virus was inoculated into mice by intramuscular or intranasal routes we observed 100% and 80% lethality respectively. The third generation of samples passaged on MDCK cell were SIV positive in indirect immunofluorescence assay (IFA) using antiserum against H1N2 SIV. Furthermore, the lungs of mice showed obvious lesion with interstitial pneumonia. Data in our study suggest that SH07 is preferentially pathogenic to mammals rather than birds although it is a reasserting virus with the fragments from swine, human and avian origin. PMID:27230301

  8. Influenza A virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Influenza A viruses are important veterinary and human health pathogens around the world. Avian influenza (AI) virus in poultry is unusual in that it can cause a range of disease symptoms from a subclinical infection to being highly virulent with 100% mortality. The difference between low pathogen...

  9. Distinct Pathogenesis of Hong Kong-Origin H5N1 Viruses in Mice Compared to That of Other Highly Pathogenic H5 Avian Influenza Viruses

    PubMed Central

    Dybing, Jody K.; Schultz-Cherry, Stacey; Swayne, David E.; Suarez, David L.; Perdue, Michael L.

    2000-01-01

    In 1997, an outbreak of virulent H5N1 avian influenza virus occurred in poultry in Hong Kong (HK) and was linked to a direct transmission to humans. The factors associated with transmission of avian influenza virus to mammals are not fully understood, and the potential risk of other highly virulent avian influenza A viruses infecting and causing disease in mammals is not known. In this study, two avian and one human HK-origin H5N1 virus along with four additional highly pathogenic H5 avian influenza viruses were analyzed for their pathogenicity in 6- to 8-week-old BALB/c mice. Both the avian and human HK H5 influenza virus isolates caused severe disease in mice, characterized by induced hypothermia, clinical signs, rapid weight loss, and 75 to 100% mortality by 6 to 8 days postinfection. Three of the non-HK-origin isolates caused no detectable clinical signs. One isolate, A/tk/England/91 (H5N1), induced measurable disease, and all but one of the animals recovered. Infections resulted in mild to severe lesions in both the upper and lower respiratory tracts. Most consistently, the viruses caused necrosis in respiratory epithelium of the nasal cavity, trachea, bronchi, and bronchioles with accompanying inflammation. The most severe and widespread lesions were observed in the lungs of HK avian influenza virus-infected mice, while no lesions or only mild lesions were evident with A/ck/Scotland/59 (H5N1) and A/ck/Queretaro/95 (H5N2). The A/ck/Italy/97 (H5N2) and the A/tk/England/91 (H5N1) viruses exhibited intermediate pathogenicity, producing mild to moderate respiratory tract lesions. In addition, infection by the different isolates could be further distinguished by the mouse immune response. The non-HK-origin isolates all induced production of increased levels of active transforming growth factor β following infection, while the HK-origin isolates did not. PMID:10627555

  10. MURINE CYTOMEGALOVIRUS HOST RESISTANCE MODELS

    EPA Science Inventory

    Mouse cytomegalovirus (MCMV) is a well developed and extremely useful and relevant host resistance model for immunotoxicity testing. at cytomegalovirus (RCMV) is currently under development and may have similar applications. ytomegaloviruses are species specific; RCMV is a distin...

  11. The contribution of PA-X to the virulence of pandemic 2009 H1N1 and highly pathogenic H5N1 avian influenza viruses

    PubMed Central

    Gao, Huijie; Sun, Yipeng; Hu, Jiao; Qi, Lu; Wang, Jinliang; Xiong, Xin; Wang, Yu; He, Qiming; Lin, Yang; Kong, Weili; Seng, Lai-Giea; Sun, Honglei; Pu, Juan; Chang, Kin-Chow; Liu, Xiufan; Liu, Jinhua

    2015-01-01

    PA-X is a novel protein encoded by PA mRNA and is found to decrease the pathogenicity of pandemic 1918 H1N1 virus in mice. However, the importance of PA-X proteins in current epidemiologically important influenza A virus strains is not known. In this study, we report on the pathogenicity and pathological effects of PA-X deficient 2009 pandemic H1N1 (pH1N1) and highly pathogenic avian influenza H5N1 viruses. We found that loss of PA-X expression in pH1N1 and H5N1 viruses increased viral replication and apoptosis in A549 cells and increased virulence and host inflammatory response in mice. In addition, PA-X deficient pH1N1 and H5N1 viruses up-regulated PA mRNA and protein synthesis and increased viral polymerase activity. Loss of PA-X was also accompanied by accelerated nuclear accumulation of PA protein and reduced suppression of PA on non-viral protein expression. Our study highlights the effects of PA-X on the moderation of viral pathogenesis and pathogenicity. PMID:25652161

  12. Susceptibility of pigeons to clade 1 and 2.2 high pathogenicity avian influenza H5N1 virus.

    PubMed

    Smietanka, Krzysztof; Minta, Zenon; Wyrostek, Krzysztof; Jóźwiak, Michal; Olszewska, Monika; Domańska-Blicharz, A Katarzyna; Reichert, A Michał; Pikuła, Anna; Habyarimana, Adelite; van den Berg, Thierry

    2011-03-01

    To assess the susceptibility of pigeons (Columba livia) to infection with H5N1 high pathogenicity avian influenza virus (HPAIV), four groups of 1-yr-old and 4-wk-old racing pigeons (10 birds in each group) were inoculated oculonasally with 106 50% egg infectious dose (EID50) of A/crested eagle/Belgium/01/2004 (clade 1) or A/swan/Poland/305-135V08/2006 (clade 2.2). Contact specific-pathogen-free (SPF) chickens were kept in the same isolators as young pigeons (two chickens per group). At 3, 5, 7, 10, and 14 days postinfection (PI) two pigeons from each infected group were selected randomly, and oropharyngeal and cloacal swabs (pigeons and contact chickens) as well as a number of internal organs (pigeons) were collected for viral RNA detection in real-time reverse transcription PCR (RRT-PCR) and histopathology. At the end of the experiment (14 days PI) blood samples from two pigeons in each group and from contact SPF chickens were also collected, and sera were tested using hemagglutination inhibition (HI) test and blocking enzyme-linked immunosorbent assay (bELISA). During the observation period all pigeons remained clinically healthy, and no gross lesions were observed in any of the infected groups. SPF contact chickens were also healthy and negative in RRT-PCR and HI tests. However, the clade 1 H5N1 virus produced more sustained infection manifested by the presence of histopathologic changes (consisting mainly of mild to moderate hemorrhagic and inflammatory lesions), prolonged persistence of viral RNA (detectable between 3 and 10 days PI) in a variety of tissues of both adult and juvenile birds (with highest RNA load in lungs and brain) as well as slight viral shedding from the trachea and cloaca, but without transmission to SPF contact chickens. Additionally, two clade 1-infected adult pigeons sacrificed at the end of experiment showed seroconversion in bELISA and HI test (using homologous virus as antigen). The viral RNA was found only at day 3 PI in one adult

  13. Origin of the diversity in DNA recognition domains in phasevarion associated modA genes of pathogenic Neisseria and Haemophilus influenzae.

    PubMed

    Gawthorne, Jayde A; Beatson, Scott A; Srikhanta, Yogitha N; Fox, Kate L; Jennings, Michael P

    2012-01-01

    Phase variable restriction-modification (R-M) systems have been identified in a range of pathogenic bacteria. In some it has been demonstrated that the random switching of the mod (DNA methyltransferase) gene mediates the coordinated expression of multiple genes and constitutes a phasevarion (phase variable regulon). ModA of Neisseria and Haemophilus influenzae contain a highly variable, DNA recognition domain (DRD) that defines the target sequence that is modified by methylation and is used to define modA alleles. 18 distinct modA alleles have been identified in H. influenzae and the pathogenic Neisseria. To determine the origin of DRD variability, the 18 modA DRDs were used to search the available databases for similar sequences. Significant matches were identified between several modA alleles and mod gene from distinct bacterial species, indicating one source of the DRD variability was via horizontal gene transfer. Comparison of DRD sequences revealed significant mosaicism, indicating exchange between the Neisseria and H. influenzae modA alleles. Regions of high inter- and intra-allele similarity indicate that some modA alleles had undergone recombination more frequently than others, generating further diversity. Furthermore, the DRD from some modA alleles, such as modA12, have been transferred en bloc to replace the DRD from different modA alleles. PMID:22457715

  14. A Single-Amino-Acid Substitution in the NS1 Protein Changes the Pathogenicity of H5N1 Avian Influenza Viruses in Mice▿

    PubMed Central

    Jiao, Peirong; Tian, Guobin; Li, Yanbing; Deng, Guohua; Jiang, Yongping; Liu, Chang; Liu, Weilong; Bu, Zhigao; Kawaoka, Yoshihiro; Chen, Hualan

    2008-01-01

    In this study, we explored the molecular basis determining the virulence of H5N1 avian influenza viruses in mammalian hosts by comparing two viruses, A/Duck/Guangxi/12/03 (DK/12) and A/Duck/Guangxi/27/03 (DK/27), which are genetically similar but differ in their pathogenicities in mice. To assess the genetic basis for this difference in virulence, we used reverse genetics to generate a series of reassortants and mutants of these two viruses. We found that a single-amino-acid substitution of serine for proline at position 42 (P42S) in the NS1 protein dramatically increased the virulence of the DK/12 virus in mice, whereas the substitution of proline for serine at the same position (S42P) completely attenuated the DK/27 virus. We further demonstrated that the amino acid S42 of NS1 is critical for the H5N1 influenza virus to antagonize host cell interferon induction and for the NS1 protein to prevent the double-stranded RNA-mediated activation of the NF-κB pathway and the IRF-3 pathway. Our results indicate that the NS1 protein is critical for the pathogenicity of H5N1 influenza viruses in mammalian hosts and that the amino acid S42 of NS1 plays a key role in undermining the antiviral immune response of the host cell. PMID:18032512

  15. Intercontinental reassortment and genomic variation of low pathogenic avian influenza viruses isolated from northern pintails (Anas acuta) in Alaska: examining the evidence through space and time

    USGS Publications Warehouse

    Ramey, Andrew M.; Pearce, John M.; Flint, Paul L.; Ip, Hon S.; Derksen, Dirk V.; Franson, J. Christian; Petrula, Michael J.; Scotton, Bradley D.; Sowl, Kristine M.; Wege, Michael L.; Trust, Kimberly A.

    2010-01-01

    Migration and population genetic data for northern pintails (Anas acuta) and phylogenetic analysis of low pathogenic avian influenza (LPAI) viruses from this host in Alaska suggest that northern pintails are involved in ongoing intercontinental transmission of avian influenza. Here, we further refine this conclusion through phylogenetic analyses which demonstrate that detection of foreign lineage gene segments is spatially dependent and consistent through time. Our results show detection of foreign lineage gene segments to be most likely at sample locations on the Alaska Peninsula and least likely along the Southern Alaska Coast. Asian lineages detected at four gene segments persisted across years, suggesting maintenance in avian hosts that migrate to Alaska each year from Asia or in hosts that remain in Alaska throughout the year. Alternatively, live viruses may persist in the environment and re-infect birds in subsequent seasons.

  16. PDlim2 Selectively Interacts with the PDZ Binding Motif of Highly Pathogenic Avian H5N1 Influenza A Virus NS1

    PubMed Central

    Wang, Yu; Li, Bo; Li, Hongyue; Li, Yapeng; Zhou, Weihong; Zhang, Cuizhu; Wang, Yingying; Rao, Zihe; Bartlam, Mark; Cao, Youjia

    2011-01-01

    The multi-functional NS1 protein of influenza A virus is a viral virulence determining factor. The last four residues at the C-terminus of NS1 constitute a type I PDZ domain binding motif (PBM). Avian influenza viruses currently in circulation carry an NS1 PBM with consensus sequence ESEV, whereas human influenza viruses bear an NS1 PBM with consensus sequence RSKV or RSEV. The PBM sequence of the influenza A virus NS1 is reported to contribute to high viral pathogenicity in animal studies. Here, we report the identification of PDlim2 as a novel binding target of the highly pathogenic avian influenza virus H5N1 strain with an NS1 PBM of ESEV (A/Chicken/Henan/12/2004/H5N1, HN12-NS1) by yeast two-hybrid screening. The interaction was confirmed by in vitro GST pull-down assays, as well as by in vivo mammalian two-hybrid assays and bimolecular fluorescence complementation assays. The binding was also confirmed to be mediated by the interaction of the PDlim2 PDZ domain with the NS1 PBM motif. Interestingly, our assays showed that PDlim2 bound specifically with HN12-NS1, but exhibited no binding to NS1 from a human influenza H1N1 virus bearing an RSEV PBM (A/Puerto Rico/8/34/H1N1, PR8-NS1). A crystal structure of the PDlim2 PDZ domain fused with the C-terminal hexapeptide from HN12-NS1, together with GST pull-down assays on PDlim2 mutants, reveals that residues Arg16 and Lys31 of PDlim2 are critical for the binding between PDlim2 and HN12-NS1. The identification of a selective binding target of HN12-NS1 (ESEV), but not PR8-NS1 (RSEV), enables us to propose a structural mechanism for the interaction between NS1 PBM and PDlim2 or other PDZ-containing proteins. PMID:21625420

  17. Highly Pathogenic Eurasian H5N8 Avian Influenza Outbreaks in Two Commercial Poultry Flocks in California.

    PubMed

    Stoute, Simone; Chin, Richard; Crossley, Beate; Gabriel Sentíes-Cué, C; Bickford, Arthur; Pantin-Jackwood, Mary; Breitmeyer, Richard; Jones, Annette; Carnaccini, Silvia; Shivaprasad, H L

    2016-09-01

    In January 2015, a highly pathogenic Eurasian lineage H5N8 avian influenza (AI) virus (AIV) was detected in a commercial meat turkey flock in Stanislaus County, CA. Approximately 3 wk later, a similar case was diagnosed in commercial brown layers from a different company located in Kings County, CA. Five 14-wk-old turkey hens were submitted to the California Animal Health and Food Safety Laboratory System (CAHFS), Turlock, and eleven 12-wk-old chickens were submitted to CAHFS, Tulare laboratory due to an acute increase in flock mortality. Gross lesions included enlarged and mottled pale spleens and pancreas in turkeys and chickens. Histologically, the major lesions observed in turkeys and chickens were splenitis, pancreatitis, encephalitis, and pneumonia. In both cases, diagnosis was based on real-time reverse transcriptase PCR (RRT-PCR), sequencing, and virus isolation from oropharyngeal and cloacal swabs. Confirmatory diagnosis and AIV characterization was done at the National Veterinary Services Laboratory, Ames, IA. The sequence of the AIV from both cases was 99% identical to an H5N8 AI virus (A/gyrfalcon/Washington/41088-6/2014) isolated from a captive gyrfalcon (Falco rusticolus) from Washington State in December 2014. Immunohistochemistry (IHC) performed on various tissues from both cases indicated a widespread AIV tissue distribution. Except for minor variations, the tissue distribution of the AI antigen was similar in the chickens and turkeys. There was positive IHC staining in the brain, spleen, pancreas, larynx, trachea, and lungs in both chickens and turkeys. Hearts, ovaries, and air sacs from the turkeys were also positive for the AI antigen. The liver sections from the chickens had occasional AI-positive staining in mononuclear cells, but the IHC on liver sections from the turkeys were negative. The bursa of Fabricius, small intestine, kidney, and skeletal muscle sections were negative for the AI antigen in both chickens and turkeys. PMID:27610732

  18. Risk factors and characteristics of H5N1 Highly Pathogenic Avian Influenza (HPAI) post-vaccination outbreaks

    PubMed Central

    Henning, Joerg; Pfeiffer, Dirk U.; Vu, Le Tri

    2009-01-01

    Highly pathogenic avian influenza (HPAI) virus H5N1 is now endemic in South-East Asia but HPAI control methods differ between countries. A widespread HPAI vaccination campaign that started at the end of 2005 in Viet Nam resulted in the cessation of poultry and human cases, but in 2006/2007 severe HPAI outbreaks re-emerged. In this study we investigated the pattern of this first post-vaccination epidemic in southern Viet Nam identifying a spatio-temporal cluster of outbreak occurrence and estimating spatially smoothed incidence rates of HPAI. Spatial risk factors associated with HPAI occurrence were identified. Medium-level poultry density resulted in an increased outbreak risk (Odds ratio (OR) = 5.4, 95% confidence interval (CI): 1.6–18.9) but also climate-vegetation factors played an important role: medium-level normalised difference vegetation indices during the rainy season from May to October were associated with higher risk of HPAI outbreaks (OR = 3.7, 95% CI: 1.7–8.1), probably because temporal flooding might have provided suitable conditions for the re-emergence of HPAI by expanding the virus distribution in the environment and by enlarging areas of possible contacts between domestic waterfowl and wild birds. On the other hand, several agricultural production factors, such as sweet potatoes yield, increased buffalo density, as well as increased electricity supply were associated with decreased risk of HPAI outbreaks. This illustrates that preventive control measures for HPAI should include a promotion of low-risk agricultural management practices as well as improvement of the infrastructure in village households. Improved HPAI vaccination efforts and coverage should focus on medium poultry density areas and on the pre-monsoon time period. PMID:19081006

  19. Risk Assessment of High Pathogenicity Avian Influenza Virus Introduction into Poland via Legal Importation of Live Poultry.

    PubMed

    Gierak, Anna; Bocian, Łukasz; Śmietanka, Krzysztof

    2016-05-01

    The risk of highly pathogenic avian influenza (HPAI) virus introduction via import of live poultry results from the probability that infected birds are exported from apparently HPAI-free areas during the silent phase of the epidemic, i.e., the period between an incursion of the virus into a susceptible population and a report on the outbreak by an exporting country. In our study we adapted a stochastic model, previously published in 2010 by Sánchez-Vizcaíno et al., with our own modifications in which the probability of HPAI introduction was assessed as the sum of the probabilities of entry of at least one infected bird from each susceptible species exported from each country into each Polish region (county). The mean annual probability of HPAI introduction into Poland via legal trade of live poultry was very low (3.07 × 10(-3), which corresponds to 1 outbreak every 326 yr). The highest risk was associated with the import of turkeys (62%) and chickens (33%). The exporting countries that contributed the most to the overall risk were Italy (31%), the Netherlands (24%), and the Czech Republic (17%). The risk was not evenly distributed across the country and it seemed higher in western, north-central, and eastern Poland while several counties of the north-west, central, or south-east parts of the country were at negligible risk. The applied model provides quantitative evidence that the risk of HPAI introduction through legal trade of poultry does not play a major role and that other paths, such as wild birds migrations or illegal trade, should be considered as the most-likely routes along which the virus can be introduced. PMID:27309053

  20. Persistence of Highly Pathogenic Avian Influenza H5N1 Virus Defined by Agro-Ecological Niche

    PubMed Central

    Hogerwerf, Lenny; Wallace, Rob G.; Ottaviani, Daniela; Slingenbergh, Jan; Prosser, Diann; Bergmann, Luc

    2010-01-01

    The highly pathogenic avian influenza (HPAI) H5N1 virus has spread across Eurasia and into Africa. Its persistence in a number of countries continues to disrupt poultry production, impairs smallholder livelihoods, and raises the risk a genotype adapted to human-to-human transmission may emerge. While previous studies identified domestic duck reservoirs as a primary risk factor associated with HPAI H5N1 persistence in poultry in Southeast Asia, little is known of such factors in countries with different agro-ecological conditions, and no study has investigated the impact of such conditions on HPAI H5N1 epidemiology at the global scale. This study explores the patterns of HPAI H5N1 persistence worldwide, and for China, Indonesia, and India includes individual provinces that have reported HPAI H5N1 presence during the 2004–2008 period. Multivariate analysis of a set of 14 agricultural, environmental, climatic, and socio-economic factors demonstrates in quantitative terms that a combination of six variables discriminates the areas with human cases and persistence: agricultural population density, duck density, duck by chicken density, chicken density, the product of agricultural population density and chicken output/input ratio, and purchasing power per capita. The analysis identifies five agro-ecological clusters, or niches, representing varying degrees of disease persistence. The agro-ecological distances of all study areas to the medoid of the niche with the greatest number of human cases are used to map HPAI H5N1 risk globally. The results indicate that few countries remain where HPAI H5N1 would likely persist should it be introduced. Electronic supplementary material The online version of this article (doi:10.1007/s10393-010-0324-z) contains supplementary material, which is available to authorized users. PMID:20585972

  1. Analysis of the crow lung transcriptome in response to infection with highly pathogenic H5N1 avian influenza virus.

    PubMed

    Vijayakumar, Periyasamy; Mishra, Anamika; Ranaware, Pradip B; Kolte, Atul P; Kulkarni, Diwakar D; Burt, David W; Raut, Ashwin Ashok

    2015-03-15

    The highly pathogenic avian influenza (HPAI) H5N1 virus, currently circulating in Asia, causes severe disease in domestic poultry as well as wild birds like crow. However, the molecular pathogenesis of HPAIV infection in crows and other wild birds is not well known. Thus, as a step to explore it, a comprehensive global gene expression analysis was performed on crow lungs, infected with HPAI H5N1 crow isolate (A/Crow/India/11TI11/2011) using high throughput next generation sequencing (NGS) (GS FLX Titanium XLR70). The reference genome of crow is not available, so RNA seq analysis was performed on the basis of a de novo assembled transcriptome. The RNA seq result shows, 4052 genes were expressed uniquely in noninfected, 6277 genes were expressed uniquely in HPAIV infected sample and of the 6814 genes expressed in both samples, 2279 genes were significantly differentially expressed. Our transcriptome profile data allows for the ability to understand the molecular mechanism behind the recent lethal HPAIV outbreak in crows which was, until recently, thought to cause lethal infections only in gallinaceous birds such as chickens, but not in wild birds. The pattern of differentially expressed genes suggest that this isolate of H5N1 virus evades the host innate immune response by attenuating interferon (IFN)-inducible signalling possibly by down regulating the signalling from type I IFN (IFNAR1 and IFNAR2) and type II IFN receptors, upregulation of the signalling inhibitors suppressor of cytokine signalling 1 (SOCS1) and SOCS3 and altering the expression of toll-like receptors (TLRs). This may be the reason for disease and mortality in crows. PMID:25592823

  2. Migration of whooper swans and outbreaks of highly pathogenic avian influenza H5N1 virus in eastern asia

    USGS Publications Warehouse

    Newman, S.H.; Iverson, S.A.; Takekawa, J.Y.; Gilbert, M.; Prosser, D.J.; Batbayar, N.; Natsagdorj, T.; Douglas, D.C.

    2009-01-01

    Evaluating the potential involvement of wild avifauna in the emergence of highly pathogenic avian influenza H5N1 (hereafter H5N1) requires detailed analyses of temporal and spatial relationships between wild bird movements and disease emergence. The death of wild swans (Cygnus spp.) has been the first indicator of the presence of H5N1 in various Asian and European countries; however their role in the geographic spread of the disease remains poorly understood. We marked 10 whooper swans (Cygnus cygnus) with GPS transmitters in northeastern Mongolia during autumn 2006 and tracked their migratory movements in relation to H5N1 outbreaks. The prevalence of H5N1 outbreaks among poultry in eastern Asia during 2003-2007 peaked during winter, concurrent with whooper swan movements into regions of high poultry density. However outbreaks involving poultry were detected year round, indicating disease perpetuation independent of migratory waterbird presence. In contrast, H5N1 outbreaks involving whooper swans, as well as other migratory waterbirds that succumbed to the disease in eastern Asia, tended to occur during seasons (late spring and summer) and in habitats (areas of natural vegetation) where their potential for contact with poultry is very low to nonexistent. Given what is known about the susceptibility of swans to H5N1, and on the basis of the chronology and rates of whooper swan migration movements, we conclude that although there is broad spatial overlap between whooper swan distributions and H5N1 outbreak locations in eastern Asia, the likelihood of direct transmission between these groups is extremely low. Thus, our data support the hypothesis that swans are best viewed as sentinel species, and moreover, that in eastern Asia, it is most likely that their infections occurred through contact with asymptomatic migratory hosts (e.g., wild ducks) at or near their breeding grounds.

  3. The Perceived Value of Passive Animal Health Surveillance: The Case of Highly Pathogenic Avian Influenza in Vietnam.

    PubMed

    Delabouglise, A; Antoine-Moussiaux, N; Phan, T D; Dao, D C; Nguyen, T T; Truong, B D; Nguyen, X N T; Vu, T D; Nguyen, K V; Le, H T; Salem, G; Peyre, M

    2016-03-01

    Economic evaluations are critical for the assessment of the efficiency and sustainability of animal health surveillance systems and the improvement of their efficiency. Methods identifying and quantifying costs and benefits incurred by public and private actors of passive surveillance systems (i.e. actors of veterinary authorities and private actors who may report clinical signs) are needed. This study presents the evaluation of perceived costs and benefits of highly pathogenic avian influenza (HPAI) passive surveillance in Vietnam. Surveys based on participatory epidemiology methods were conducted in three provinces in Vietnam to collect data on costs and benefits resulting from the reporting of HPAI suspicions to veterinary authorities. A quantitative tool based on stated preference methods and participatory techniques was developed and applied to assess the non-monetary costs and benefits. The study showed that poultry farmers are facing several options regarding the management of HPAI suspicions, besides reporting the following: treatment, sale or destruction of animals. The option of reporting was associated with uncertain outcome and transaction costs. Besides, actors anticipated the release of health information to cause a drop of markets prices. This cost was relevant at all levels, including farmers, veterinary authorities and private actors of the upstream sector (feed, chicks and medicine supply). One benefit associated with passive surveillance was the intervention of public services to clean farms and the environment to limit the disease spread. Private actors of the poultry sector valued information on HPAI suspicions (perceived as a non-monetary benefit) which was mainly obtained from other private actors and media. PMID:26146982

  4. Persistence of highly pathogenic avian influenza H5N1 virus defined by agro-ecological niche.

    PubMed

    Hogerwerf, Lenny; Wallace, Rob G; Ottaviani, Daniela; Slingenbergh, Jan; Prosser, Diann; Bergmann, Luc; Gilbert, Marius

    2010-06-01

    The highly pathogenic avian influenza (HPAI) H5N1 virus has spread across Eurasia and into Africa. Its persistence in a number of countries continues to disrupt poultry production, impairs smallholder livelihoods, and raises the risk a genotype adapted to human-to-human transmission may emerge. While previous studies identified domestic duck reservoirs as a primary risk factor associated with HPAI H5N1 persistence in poultry in Southeast Asia, little is known of such factors in countries with different agro-ecological conditions, and no study has investigated the impact of such conditions on HPAI H5N1 epidemiology at the global scale. This study explores the patterns of HPAI H5N1 persistence worldwide, and for China, Indonesia, and India includes individual provinces that have reported HPAI H5N1 presence during the 2004-2008 period. Multivariate analysis of a set of 14 agricultural, environmental, climatic, and socio-economic factors demonstrates in quantitative terms that a combination of six variables discriminates the areas with human cases and persistence: agricultural population density, duck density, duck by chicken density, chicken density, the product of agricultural population density and chicken output/input ratio, and purchasing power per capita. The analysis identifies five agro-ecological clusters, or niches, representing varying degrees of disease persistence. The agro-ecological distances of all study areas to the medoid of the niche with the greatest number of human cases are used to map HPAI H5N1 risk globally. The results indicate that few countries remain where HPAI H5N1 would likely persist should it be introduced. PMID:20585972

  5. Persistence of highly pathogenic avian influenza H5N1 virus defined by agro-ecological niche

    USGS Publications Warehouse

    Hogerwerf, Lenny; Wallace, Rob G.; Ottaviani, Daniela; Slingenbergh, Jan; Prosser, Diann; Bergmann, Luc; Gilbert, Marius

    2010-01-01

    The highly pathogenic avian influenza (HPAI) H5N1 virus has spread across Eurasia and into Africa. Its persistence in a number of countries continues to disrupt poultry production, impairs smallholder livelihoods, and raises the risk a genotype adapted to human-to-human transmission may emerge. While previous studies identified domestic duck reservoirs as a primary risk factor associated with HPAI H5N1 persistence in poultry in Southeast Asia, little is known of such factors in countries with different agro-ecological conditions, and no study has investigated the impact of such conditions on HPAI H5N1 epidemiology at the global scale. This study explores the patterns of HPAI H5N1 persistence worldwide, and for China, Indonesia, and India includes individual provinces that have reported HPAI H5N1 presence during the 2004–2008 period. Multivariate analysis of a set of 14 agricultural, environmental, climatic, and socio-economic factors demonstrates in quantitative terms that a combination of six variables discriminates the areas with human cases and persistence: agricultural population density, duck density, duck by chicken density, chicken density, the product of agricultural population density and chicken output/input ratio, and purchasing power per capita. The analysis identifies five agro-ecological clusters, or niches, representing varying degrees of disease persistence. The agro-ecological distances of all study areas to the medoid of the niche with the greatest number of human cases are used to map HPAI H5N1 risk globally. The results indicate that few countries remain where HPAI H5N1 would likely persist should it be introduced.

  6. Migration of whooper swans and outbreaks of highly pathogenic avian influenza H5N1 virus in Eastern Asia

    USGS Publications Warehouse

    Newman, Scott H.; Iverson, Samuel A.; Takekawa, John Y.; Gilbert, Martin; Prosser, Diann J.; Batbayar, Nyambyar; Natsagdorj, Tseveenmyadag; Douglas, David C.

    2009-01-01

    Evaluating the potential involvement of wild avifauna in the emergence of highly pathogenic avian influenza H5N1 (hereafter H5N1) requires detailed analyses of temporal and spatial relationships between wild bird movements and disease emergence. The death of wild swans (Cygnus spp.) has been the first indicator of the presence of H5N1 in various Asian and European countries; however their role in the geographic spread of the disease remains poorly understood. We marked 10 whooper swans (Cygnus cygnus) with GPS transmitters in northeastern Mongolia during autumn 2006 and tracked their migratory movements in relation to H5N1 outbreaks. The prevalence of H5N1 outbreaks among poultry in eastern Asia during 2003-2007 peaked during winter, concurrent with whooper swan movements into regions of high poultry density. However outbreaks involving poultry were detected year round, indicating disease perpetuation independent of migratory waterbird presence. In contrast, H5N1 outbreaks involving whooper swans, as well as other migratory waterbirds that succumbed to the disease in eastern Asia, tended to occur during seasons (late spring and summer) and in habitats (areas of natural vegetation) where their potential for contact with poultry is very low to nonexistent. Given what is known about the susceptibility of swans to H5N1, and on the basis of the chronology and rates of whooper swan migration movements, we conclude that although there is broad spatial overlap between whooper swan distributions and H5N1 outbreak locations in eastern Asia, the likelihood of direct transmission between these groups is extremely low. Thus, our data support the hypothesis that swans are best viewed as sentinel species, and moreover, that in eastern Asia, it is most likely that their infections occurred through contact with asymptomatic migratory hosts (e.g., wild ducks) at or near their breeding grounds.

  7. Molecular and antigenic evolution and geographical spread of H5N1 highly pathogenic avian influenza viruses in western Africa.

    PubMed

    Ducatez, M F; Olinger, C M; Owoade, A A; Tarnagda, Z; Tahita, M C; Sow, A; De Landtsheer, S; Ammerlaan, W; Ouedraogo, J B; Osterhaus, A D M E; Fouchier, R A M; Muller, C P

    2007-08-01

    In Africa, highly pathogenic avian influenza H5N1 virus was first detected in northern Nigeria and later also in other regions of the country. Since then, seven other African countries have reported H5N1 infections. This study reports a comparison of full-length genomic sequences of H5N1 isolates from seven chicken farms in Nigeria and chicken and hooded vultures in Burkina Faso with earlier H5N1 outbreaks worldwide. In addition, the antigenicity of Nigerian H5N1 isolates was compared with earlier strains. All African strains clustered within three sublineages denominated A (south-west Nigeria, Niger), B (south-west Nigeria, Egypt, Djibouti) and C (northern Nigeria, Burkina Faso, Sudan, Côte d'Ivoire), with distinct nucleotide and amino acid signatures and distinct geographical distributions within Africa. Probable non-African ancestors within the west Asian/Russian/European lineage distinct from the south-east Asian lineages were identified for each sublineage. All reported human cases in Africa were caused by sublineage B. Substitution rates were calculated on the basis of sequences from 11 strains from a single farm in south-west Nigeria. As H5N1 emerged essentially at the same time in the north and south-west of Nigeria, the substitution rates confirmed that the virus probably did not spread from the north to the south, given the observed sequence diversity, but that it entered the country via three independent introductions. The strains from Burkina Faso seemed to originate from northern Nigeria. At least two of the sublineages also circulated in Europe in 2006 as seen in Germany, further suggesting that the sublineages had already emerged outside of Africa and seemed to have followed the east African/west Asian and Black Sea/Mediterranean flyways of migratory birds. PMID:17622635

  8. Experimental challenge and pathology of highly pathogenic avian influenza virus H5N1 in dunlin (Calidris alpina), an intercontinental migrant shorebird species

    PubMed Central

    Hall, Jeffrey S.; Franson, J. Christian; Gill, Robert E.; Meteyer, Carol U.; TeSlaa, Joshua L.; Nashold, Sean; Dusek, Robert J.; Ip, Hon S.

    2011-01-01

    Please cite this paper as: Hall et al. (2011). Experimental challenge and pathology of highly pathogenic avian influenza virus H5N1 in dunlin (Calidris alpina), an intercontinental migrant shorebird species. Influenza and Other Respiratory Viruses 5(5), 365–372. Background  Shorebirds (Charadriiformes) are considered one of the primary reservoirs of avian influenza. Because these species are highly migratory, there is concern that infected shorebirds may be a mechanism by which highly pathogenic avian influenza virus (HPAIV) H5N1 could be introduced into North America from Asia. Large numbers of dunlin (Calidris alpina) migrate from wintering areas in central and eastern Asia, where HPAIV H5N1 is endemic, across the Bering Sea to breeding areas in Alaska. Low pathogenic avian influenza virus has been previously detected in dunlin, and thus, dunlin represent a potential risk to transport HPAIV to North America. To date no experimental challenge studies have been performed in shorebirds. Methods  Wild dunlin were inoculated intranasally and intrachoanally various doses of HPAIV H5N1. The birds were monitored daily for virus excretion, disease signs, morbidity, and mortality. Results  The infectious dose of HPAIV H5N1 in dunlin was determined to be 101.7 EID50/100 μl and that the lethal dose was 101.83 EID50/100 μl. Clinical signs were consistent with neurotropic disease, and histochemical analyses revealed that infection was systemic with viral antigen and RNA most consistently found in brain tissues. Infected birds excreted relatively large amounts of virus orally (104 EID50) and smaller amounts cloacally. Conclusions  Dunlin are highly susceptible to infection with HPAIV H5N1. They become infected after exposure to relatively small doses of the virus and if they become infected, they are most likely to suffer mortality within 3–5 days. These results have important implications regarding the risks of transport and transmission of HPAIV H5N1 to North

  9. Avian influenza

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza (AI) viruses infect domestic poultry and wild birds. In domestic poultry, AI viruses are typically of low pathogenicity (LP) causing subclinical infections, respiratory disease or drops in egg production. However, a few AI viruses cause severe systemic disease with high mortality; i....

  10. AVIAN INFLUENZA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian Influenza (AI) viruses infect domestic poultry and wild birds. In domestic poultry, AI viruses are typically of low pathogenicity (LP) causing subclinical infections, respiratory disease or drops in egg production. However, a few AI viruses cause severe systemic disease with high mortality; ...

  11. Environmental correlates of H5N2 low pathogenicity avian influenza outbreak heterogeneity in domestic poultry in Italy.

    PubMed

    Mughini-Gras, Lapo; Bonfanti, Lebana; Mulatti, Paolo; Monne, Isabella; Guberti, Vittorio; Cordioli, Paolo; Marangon, Stefano

    2014-01-01

    Italy has experienced recurrent incursions of H5N2 avian influenza (AI) viruses in different geographical areas and varying sectors of the domestic poultry industry. Considering outbreak heterogeneity rather than treating all outbreaks of low pathogenicity AI (LPAI) viruses equally is important given their interactions with the environment and potential to spread, evolve and increase pathogenicity. This study aims at identifying potential environmental drivers of H5N2 LPAI outbreak occurrence in time, space and poultry populations. Thirty-four environmental variables were tested for association with the characteristics of 27 H5N2 LPAI outbreaks (i.e. time, place, flock type, number and species of birds affected) occurred among domestic poultry flocks in Italy in 2010-2012. This was done by applying a recently proposed analytical approach based on a combined non-metric multidimensional scaling, clustering and regression analysis. Results indicated that the pattern of (dis)similarities among the outbreaks entailed an underlying structure that may be the outcome of large-scale, environmental interactions in ecological dimension. Increased densities of poultry breeders, and increased land coverage by industrial, commercial and transport units were associated with increased heterogeneity in outbreak characteristics. In areas with high breeder densities and with many infrastructures, outbreaks affected mainly industrial turkey/layer flocks. Outbreaks affecting ornamental, commercial and rural multi-species flocks occurred mainly in lowly infrastructured areas of northern Italy. Outbreaks affecting rural layer flocks occurred mainly in areas with low breeder densities in south-central Italy. In savannah-like environments, outbreaks affected mainly commercial flocks of galliformes. Suggestive evidence that ecological ordination makes sense genetically was also provided, as virus strains showing high genetic similarity clustered into ecologically similar outbreaks. Findings

  12. Environmental Correlates of H5N2 Low Pathogenicity Avian Influenza Outbreak Heterogeneity in Domestic Poultry in Italy

    PubMed Central

    Mughini-Gras, Lapo; Bonfanti, Lebana; Mulatti, Paolo; Monne, Isabella; Guberti, Vittorio; Cordioli, Paolo; Marangon, Stefano

    2014-01-01

    Italy has experienced recurrent incursions of H5N2 avian influenza (AI) viruses in different geographical areas and varying sectors of the domestic poultry industry. Considering outbreak heterogeneity rather than treating all outbreaks of low pathogenicity AI (LPAI) viruses equally is important given their interactions with the environment and potential to spread, evolve and increase pathogenicity. This study aims at identifying potential environmental drivers of H5N2 LPAI outbreak occurrence in time, space and poultry populations. Thirty-four environmental variables were tested for association with the characteristics of 27 H5N2 LPAI outbreaks (i.e. time, place, flock type, number and species of birds affected) occurred among domestic poultry flocks in Italy in 2010–2012. This was done by applying a recently proposed analytical approach based on a combined non-metric multidimensional scaling, clustering and regression analysis. Results indicated that the pattern of (dis)similarities among the outbreaks entailed an underlying structure that may be the outcome of large-scale, environmental interactions in ecological dimension. Increased densities of poultry breeders, and increased land coverage by industrial, commercial and transport units were associated with increased heterogeneity in outbreak characteristics. In areas with high breeder densities and with many infrastructures, outbreaks affected mainly industrial turkey/layer flocks. Outbreaks affecting ornamental, commercial and rural multi-species flocks occurred mainly in lowly infrastructured areas of northern Italy. Outbreaks affecting rural layer flocks occurred mainly in areas with low breeder densities in south-central Italy. In savannah-like environments, outbreaks affected mainly commercial flocks of galliformes. Suggestive evidence that ecological ordination makes sense genetically was also provided, as virus strains showing high genetic similarity clustered into ecologically similar outbreaks

  13. Characterization of Low Pathogenic Avian Influenza Virus Subtype H9N2 Isolated from Free-Living Mynah Birds (Acridotheres tristis) in the Sultanate of Oman.

    PubMed

    Body, Mohammad H; Alrarawahi, Abdulmajeed H; Alhubsy, Saif S; Saravanan, Nirmala; Rajmony, Sunil; Mansoor, Muhammad Khalid

    2015-06-01

    A low pathogenic avian influenza virus was identified from free-living birds (mynah, Acridotheres tristis) of the starling family. Virus was isolated by inoculation of homogenized suspension from lung, tracheal, spleen, and cloacal swabs into the allantoic cavity of embryonated chicken eggs. Subtype of the isolate was characterized as H9N2 by hemagglutination inhibition test using monospecific chicken antisera to a wide range of influenza reference strain. Pathogenicity of the isolate was determined by intravenous pathogenicity index. The virus was reisolated from experimentally infected chicken. Additionally, the isolate was subjected to reverse transcriptase PCR using partial hemagglutinin (HA) gene-specific primers and yielded an amplicon of 487 bp. HA gene sequence analysis revealed 99% sequence homology among mynah and chicken isolates from Oman. On phylogenetic analysis, isolates from mynah (A/mynnah/Oman/AIVS6/2005) and chicken (A/chicken/Oman/AIVS3/2006; A/chicken/Oman/AIVS7/2006) clustered together tightly, indicating these free-flying birds may be a source of introduction of H9N2 subtype in poultry bird in Oman. Moreover, the HA gene of H9N2 isolates from Oman resembled those of viruses of the G1-like lineage and were very similar to those from United Arab Emirates. PMID:26473686

  14. PB2 residue 158 is a pathogenic determinant of pandemic H1N1 and H5 influenza a viruses in mice.

    PubMed

    Zhou, Bin; Li, Yan; Halpin, Rebecca; Hine, Erin; Spiro, David J; Wentworth, David E

    2011-01-01

    Influenza A viruses are human and animal pathogens that cause morbidity and mortality, which range from mild to severe. The 2009 H1N1 pandemic was caused by the emergence of a reassortant H1N1 subtype (H1N1pdm) influenza A virus containing gene segments that originally circulated in human, avian, and swine virus reservoirs. The molecular determinants of replication and pathogenesis of H1N1pdm viruses in humans and other mammals are poorly understood. Therefore, we set out to elucidate viral determinants critical to the pathogenesis of this novel reassortant using a mouse model. We found that a glutamate-to-glycine substitution at residue 158 of the PB2 gene (PB2-E158G) increased the morbidity and mortality of the parental H1N1pdm virus. Results from mini-genome replication assays in human cells and virus titration in mouse tissues demonstrated that PB2-E158G is a pathogenic determinant, because it significantly increases viral replication rates. The virus load in PB2-E158G-infected mouse lungs was 1,300-fold higher than that of the wild-type virus. Our data also show that PB2-E158G had a much stronger influence on the RNA replication and pathogenesis of H1N1pdm viruses than PB2-E627K, which is a known pathogenic determinant. Remarkably, PB2-E158G substitutions also altered the pathotypes of two avian H5 viruses in mice, indicating that this residue impacts genetically divergent influenza A viruses and suggesting that this region of PB2 could be a new antiviral target. Collectively, the data presented in this study demonstrate that PB2-E158G is a novel pathogenic determinant of influenza A viruses in the mouse model. We speculate that PB2-E158G may be important in the adaptation of avian PB2 genes to other mammals, and BLAST sequence analysis identified a naturally occurring human H1N1pdm isolate that has this substitution. Therefore, future surveillance efforts should include scrutiny of this region of PB2 because of its potential impact on pathogenesis. PMID

  15. Protective efficacy of stockpiled vaccine against H5N8 highly pathogenic avian influenza virus isolated from a chicken in Kumamoto prefecture, Japan, in 2014

    PubMed Central

    GAMOH, Koichiro; NAKAMIZO, Mari; OKAMATSU, Masatoshi; SAKODA, Yoshihiro; KIDA, Hiroshi; SUZUKI, Shoko

    2015-01-01

    H5 highly pathogenic avian influenza (HPAI) viruses have spread worldwide, and antigenic variants of different clades have been selected. In this study, the national stockpiled vaccine prepared from A/duck/Hokkaido/Vac-1/2004 (H5N1) strain was evaluated for the protective efficacy against H5N8 HPAI virus isolated in Kumamoto prefecture, Japan, in April 2014. In the challenge test, all of the vaccinated chickens survived without showing any clinical signs and reduced virus shedding. It was concluded that the present stockpiled vaccine was effective against the H5N8 HPAI virus. PMID:26290130

  16. Low Virulence and Lack of Airborne Transmission of the Dutch Highly Pathogenic Avian Influenza Virus H5N8 in Ferrets

    PubMed Central

    van den Brand, Judith M. A.; Lexmond, Pascal; Bestebroer, Theo M.; Rimmelzwaan, Guus F.; Koopmans, Marion; Kuiken, Thijs; Fouchier, Ron A. M.

    2015-01-01

    Highly pathogenic avian influenza (HPAI) H5N8 viruses that emerged in poultry in East Asia spread to Europe and North America by late 2014. Here we show that the European HPAI H5N8 viruses differ from the Korean and Japanese HPAI H5N8 viruses by several amino acids and that a Dutch HPAI H5N8 virus had low virulence and was not transmitted via the airborne route in ferrets. The virus did not cross-react with sera raised against pre-pandemic H5 vaccine strains. This data is useful for public health risk assessments. PMID:26090682

  17. Long-term surveillance of H7 influenza viruses in American wild aquatic birds: are the H7N3 influenza viruses in wild birds the precursors of highly pathogenic strains in domestic poultry?

    PubMed Central

    Krauss, Scott; Stucker, Karla M; Schobel, Seth A; Danner, Angela; Friedman, Kimberly; Knowles, James P; Kayali, Ghazi; Niles, Lawrence J; Dey, Amanda D; Raven, Garnet; Pryor, Paul; Lin, Xudong; Das, Suman R; Stockwell, Timothy B; Wentworth, David E; Webster, Robert G

    2015-01-01

    The emergence of influenza A virus (IAV) in domestic avian species and associated transmissions to mammals is unpredictable. In the Americas, the H7 IAVs are of particular concern, and there have been four separate outbreaks of highly pathogenic (HP) H7N3 in domestic poultry in North and South America between 2002 and 2012, with occasional spillover into humans. Here, we use long-term IAV surveillance in North American shorebirds at Delaware Bay, USA, from 1985 to 2012 and in ducks in Alberta, Canada, from 1976 to 2012 to determine which hemagglutinin (HA)–neuraminidase (NA) combinations predominated in Anseriformes (ducks) and Charadriiformes (shorebirds) and whether there is concordance between peaks of H7 prevalence and transmission in wild aquatic birds and the emergence of H7 IAVs in poultry and humans. Whole-genome sequencing supported phylogenetic and genomic constellation analyses to determine whether HP IAVs emerge in the context of specific internal gene segment sequences. Phylogenetic analysis of whole-genome sequences of the H7N3 influenza viruses from wild birds and HP H7N3 outbreaks in the Americas indicate that each HP outbreak was an independent emergence event and that the low pathogenic (LP) avian influenza precursors were most likely from dabbling ducks. The different polybasic cleavage sites in the four HP outbreaks support independent origins. At the 95% nucleotide percent identity-level phylogenetic analysis showed that the wild duck HA, PB1, and M sequences clustered with the poultry and human outbreak sequences. The genomic constellation analysis strongly suggests that gene segments/virus flow from wild birds to domestic poultry. PMID:26954883

  18. 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

  19. Reassortant H5N1 avian influenza viruses containing PA or NP gene from an H9N2 virus significantly increase the pathogenicity in mice.

    PubMed

    Hao, Xiaoli; Hu, Jiao; Wang, Jiongjiong; Xu, Jing; Cheng, Hao; Xu, Yunpeng; Li, Qunhui; He, Dongchang; Liu, Xiaowen; Wang, Xiaoquan; Gu, Min; Hu, Shunlin; Xu, Xiulong; Liu, Huimou; Chen, Sujuan; Peng, Daxin; Liu, Xiufan

    2016-08-30

    Reassortment between different influenza viruses is a crucial way to generate novel influenza viruses with unpredictable virulence and transmissibility, which may threaten the public health. As currently in China, avian influenza viruses (AIVs) of H9N2 and H5N1 subtypes are endemic in poultry in many areas, while they are prone to reassort with each other naturally. In order to evaluate the risk of the reassortment to public health, A/Goose/Jiangsu/k0403/2010 [GS/10(H5N1)] virus was used as a backbone to generate a series of reassortants, each contained a single internal gene derived from the predominant S genotype of the A/Chicken/Jiangsu/WJ57/2012 [WJ/57(H9N2)]. We next assessed the biological characteristics of these assortments, including pathogenicity, replication efficiency and polymerase activity. We found that the parental WJ/57(H9N2) and GS/10(H5N1) viruses displayed high genetic compatibility. Notably, the H5N1 reassortants containing the PA or NP gene from WJ/57(H9N2) virus significantly increased virulence and replication ability in mice, as well as markedly enhanced polymerase activity. Our results indicate that the endemicity of H9N2 and H5N1 in domestic poultry greatly increases the possibility of generating new viruses by reassortment that may pose a great threat to poultry industry and public health. PMID:27527770

  20. Immunization with Plant-Expressed Hemagglutinin Protects Chickens from Lethal Highly Pathogenic Avian Influenza Virus H5N1 Challenge Infection▿

    PubMed Central

    Kalthoff, Donata; Giritch, Anatoli; Geisler, Katharina; Bettmann, Ulrike; Klimyuk, Victor; Hehnen, Hans-Robert; Gleba, Yuri; Beer, Martin

    2010-01-01

    Highly pathogenic avian influenza (HPAI) is a striking disease in susceptible poultry, which leads to severe economic losses. Inactivated vaccines are the most widely used vaccines in avian influenza virus (AIV) vaccination programs. However, these vaccines interfere with the serological detection of wild-type AIV infections in immunized populations. The use of vaccines that allow differentiation between infected and vaccinated animals (DIVA strategy) would stop current stamping-out policies. Therefore, novel vaccination strategies are needed to allow improved protection of animals and humans against HPAI virus (HPAIV) infection. The presented study analyzed for the first time the immunogenic capacity of plant-expressed full-length hemagglutinin (rHA0) of HPAIV H5N1 in several vaccine formulations within the highly relevant host species chicken. We were able to express plant-expressed rHA0 at high levels and could show that, when administered with potent adjuvants, it is highly immunogenic and can fully protect chicken against lethal challenge infection. Real-time reverse transcription (RT)-PCR and serological tests demonstrated only marginally increased virus replication in animals vaccinated with plant-derived rHA0 compared to animals immunized with an inactivated reference vaccine. In addition, the use of plant-expressed rHA0 also allowed an easy serological differentiation of vaccinated from AIV-infected animals based on antibodies against the influenza virus NP protein. PMID:20810729

  1. 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

    2016-01-01

    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

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

    PubMed Central

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

    2015-01-01

    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. PMID:26583382

  3. 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. PMID:26583382

  4. 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

  5. Hearing Loss and Cytomegalovirus.

    ERIC Educational Resources Information Center

    Strauss, Melvin

    1997-01-01

    Cytomegalovirus is the most common cause of congenital virally induced hearing loss. Maternal infection is most often asymptomatic as is the infection in the newborn. Hearing loss occurs in both clinically apparent infection and in the asymptomatic infection. Current methods of detection, treatment, and prevention and research efforts are…

  6. Continuing challenges in influenza

    PubMed Central

    Webster, Robert G.; Govorkova, Elena A.

    2014-01-01

    Influenza is an acute respiratory disease in mammals and domestic poultry that emerges from zoonotic reservoirs in aquatic birds and bats. Although influenza viruses are among the most intensively studied pathogens, existing control options require further improvement. Influenza vaccines must be regularly updated because of continuous antigenic drift and sporadic antigenic shifts in the viral surface glycoproteins. Currently, influenza therapeutics are limited to neuraminidase inhibitors; novel drugs and vaccine approaches are therefore urgently needed. Advances in vaccinology and structural analysis have revealed common antigenic epitopes on hemagglutinins across all influenza viruses and suggest that a universal influenza vaccine is possible. In addition, various immunomodulatory agents and signaling pathway inhibitors are undergoing preclinical development. Continuing challenges in influenza include the emergence of pandemic H1N1 influenza in 2009, human infections with avian H7N9 influenza in 2013, and sporadic human cases of highly pathogenic avian H5N1 influenza. Here, we review the challenges facing influenza scientists and veterinary and human public health officials; we also discuss the exciting possibility of achieving the ultimate goal of controlling influenza’s ability to change its antigenicity. PMID:24891213

  7. Twenty amino acids at the C-terminus of PA-X are associated with increased influenza A virus replication and pathogenicity

    PubMed Central

    Gao, Huijie; Sun, Honglei; Hu, Jiao; Qi, Lu; Wang, Jinliang; Xiong, Xin; Wang, Yu; He, Qiming; Lin, Yang; Kong, Weili; Seng, Lai-Giea; Pu, Juan; Chang, Kin-Chow; Liu, Xiufan; Liu, Jinhua

    2015-01-01

    The PA-X protein, arising from ribosomal frameshift during PA translation, was recently discovered in influenza A virus (IAV). The C-terminal domain ‘X’ of PA-X proteins in IAVs can be classified as full-length (61 aa) or truncated (41 aa). In the main, avian influenza viruses express full-length PA-X proteins, whilst 2009 pandemic H1N1 (pH1N1) influenza viruses harbour truncated PA proteins. The truncated form lacks aa 232–252 of the full-length PA-X protein. The significance of PA-X length in virus function remains unclear. To address this issue, we constructed a set of contemporary influenza viruses (pH1N1, avian H5N1 and H9N2) with full and truncated PA-X by reverse genetics to compare their replication and host pathogenicity. All full-length PA-X viruses in human A549 cells conferred 10- to 100-fold increase in viral replication and 5–8 % increase in apoptosis relative to corresponding truncated PA-X viruses. Full-length PA-X viruses were more virulent and caused more severe inflammatory responses in mice. Furthermore, aa 233–252 at the C terminus of PA-X strongly suppressed co-transfected gene expression by ∼50 %, suggesting that these terminal 20 aa could play a role in enhancing viral replication and contribute to virulence. PMID:25877935

  8. Intranasal vaccination with a plant-derived H5 HA vaccine protects mice and ferrets against highly pathogenic avian influenza virus challenge.

    PubMed

    Major, Diane; Chichester, Jessica A; Pathirana, Rishi D; Guilfoyle, Kate; Shoji, Yoko; Guzman, Carlos A; Yusibov, Vidadi; Cox, Rebecca J

    2015-01-01

    Highly pathogenic avian influenza H5N1 infection remains a public health threat and vaccination is the best measure of limiting the impact of a potential pandemic. Mucosal vaccines have the advantage of eliciting immune responses at the site of viral entry, thereby preventing infection as well as further viral transmission. In this study, we assessed the protective efficacy of hemagglutinin (HA) from the A/Indonesia/05/05 (H5N1) strain of influenza virus that was produced by transient expression in plants. The plant-derived vaccine, in combination with the mucosal adjuvant (3',5')-cyclic dimeric guanylic acid (c-di-GMP) was used for intranasal immunization of mice and ferrets, before challenge with a lethal dose of the A/Indonesia/05/05 (H5N1) virus. Mice vaccinated with 15 μg or 5 μg of adjuvanted HA survived the viral challenge, while all control mice died within 10 d of challenge. Vaccinated animals elicited serum hemagglutination inhibition, IgG and IgA antibody titers. In the ferret challenge study, all animals vaccinated with the adjuvanted plant vaccine survived the lethal viral challenge, while 50% of the control animals died. In both the mouse and ferret models, the vaccinated animals were better protected from weight loss and body temperature changes associated with H5N1 infection compared with the non-vaccinated controls. Furthermore, the systemic spread of the virus was lower in the vaccinated animals compared with the controls. Results presented here suggest that the plant-produced HA-based influenza vaccine adjuvanted with c-di-GMP is a promising vaccine/adjuvant combination for the development of new mucosal influenza vaccines. PMID:25714901

  9. LabDisk with complete reagent prestorage for sample-to-answer nucleic acid based detection of respiratory pathogens verified with influenza A H3N2 virus.

    PubMed

    Stumpf, F; Schwemmer, F; Hutzenlaub, T; Baumann, D; Strohmeier, O; Dingemanns, G; Simons, G; Sager, C; Plobner, L; von Stetten, F; Zengerle, R; Mark, D

    2016-01-01

    Portable point-of-care devices for pathogen detection require easy, minimal and user-friendly handling steps and need to have the same diagnostic performance compared to centralized laboratories. In this work we present a fully automated sample-to-answer detection of influenza A H3N2 virus in a centrifugal LabDisk with complete prestorage of reagents. Thus, the initial supply of the sample remains the only manual handling step. The self-contained LabDisk automates by centrifugal microfluidics all necessary process chains for PCR-based pathogen detection: pathogen lysis, magnetic bead based nucleic acid extraction, aliquoting of the eluate into 8 reaction cavities, and real-time reverse transcription polymerase chain reaction (RT-PCR). Prestored reagents comprise air dried specific primers and fluorescence probes, lyophilized RT-PCR mastermix and stick-packaged liquid reagents for nucleic acid extraction. Employing two different release frequencies for the stick-packaged liquid reagents enables on-demand release of highly wetting extraction buffers, such as sequential release of lysis and binding buffer. Microfluidic process-flow was successful in 54 out of 55 tested LabDisks. We demonstrate successful detection of the respiratory pathogen influenza A H3N2 virus in a total of 18 LabDisks with sample concentrations down to 2.39 × 10(4) viral RNA copies per ml, which is in the range of clinical relevance. Furthermore, we detected RNA bacteriophage MS2 acting as internal control in 3 LabDisks with a sample concentration down to 75 plaque forming units (pfu) per ml. All experiments were applied in a 2 kg portable, laptop controlled point-of-care device. The turnaround time of the complete analysis from sample-to-answer was less than 3.5 hours. PMID:26610171

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

    PubMed Central

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

    2012-01-01

    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. PMID:22875253

  11. Spatial distribution and risk factors of highly pathogenic avian influenza (HPAI) H5N1 in China

    USGS Publications Warehouse

    Martin, V.; Pfeiffer, D.U.; Zhou, X.; Xiao, X.; Prosser, D.J.; Guo, F.; Gilbert, M.

    2011-01-01

    Highly pathogenic avian influenza (HPAI) H5N1 was first encountered in 1996 in Guangdong province (China) and started spreading throughout Asia and the western Palearctic in 2004-2006. Compared to several other countries where the HPAI H5N1 distribution has been studied in some detail, little is known about the environmental correlates of the HPAI H5N1 distribution in China. HPAI H5N1 clinical disease outbreaks, and HPAI virus (HPAIV) H5N1 isolated from active risk-based surveillance sampling of domestic poultry (referred to as HPAIV H5N1 surveillance positives in this manuscript) were modeled separately using seven risk variables: chicken, domestic waterfowl population density, proportion of land covered by rice or surface water, cropping intensity, elevation, and human population density. We used bootstrapped logistic regression and boosted regression trees (BRT) with cross-validation to identify the weight of each variable, to assess the predictive power of the models, and to map the distribution of HPAI H5N1 risk. HPAI H5N1 clinical disease outbreak occurrence in domestic poultry was mainly associated with chicken density, human population density, and elevation. In contrast, HPAIV H5N1 infection identified by risk-based surveillance was associated with domestic waterfowl density, human population density, and the proportion of land covered by surface water. Both models had a high explanatory power (mean AUC ranging from 0.864 to 0.967). The map of HPAIV H5N1 risk distribution based on active surveillance data emphasized areas south of the Yangtze River, while the distribution of reported outbreak risk extended further North, where the density of poultry and humans is higher. We quantified the statistical association between HPAI H5N1 outbreak, HPAIV distribution and post-vaccination levels of seropositivity (percentage of effective post-vaccination seroconversion in vaccinated birds) and found that provinces with either outbreaks or HPAIV H5N1 surveillance

  12. Spatial distribution and risk factors of highly pathogenic avian influenza (HPAI) H5N1 in China

    USGS Publications Warehouse

    Martin, Vincent; Pfeiffer, Dirk U.; Zhou, Xiaoyan; Xiao, Xiangming; Prosser, Diann J.; Guo, Fusheng; Gilbert, Marius

    2011-01-01

    Highly pathogenic avian influenza (HPAI) H5N1 was first encountered in 1996 in Guangdong province (China) and started spreading throughout Asia and the western Palearctic in 2004–2006. Compared to several other countries where the HPAI H5N1 distribution has been studied in some detail, little is known about the environmental correlates of the HPAI H5N1 distribution in China. HPAI H5N1 clinical disease outbreaks, and HPAI virus (HPAIV) H5N1 isolated from active risk-based surveillance sampling of domestic poultry (referred to as HPAIV H5N1 surveillance positives in this manuscript) were modeled separately using seven risk variables: chicken, domestic waterfowl population density, proportion of land covered by rice or surface water, cropping intensity, elevation, and human population density. We used bootstrapped logistic regression and boosted regression trees (BRT) with cross-validation to identify the weight of each variable, to assess the predictive power of the models, and to map the distribution of HPAI H5N1 risk. HPAI H5N1 clinical disease outbreak occurrence in domestic poultry was mainly associated with chicken density, human population density, and elevation. In contrast, HPAIV H5N1 infection identified by risk-based surveillance was associated with domestic waterfowl density, human population density, and the proportion of land covered by surface water. Both models had a high explanatory power (mean AUC ranging from 0.864 to 0.967). The map of HPAIV H5N1 risk distribution based on active surveillance data emphasized areas south of the Yangtze River, while the distribution of reported outbreak risk extended further North, where the density of poultry and humans is higher. We quantified the statistical association between HPAI H5N1 outbreak, HPAIV distribution and post-vaccination levels of seropositivity (percentage of effective post-vaccination seroconversion in vaccinated birds) and found that provinces with either outbreaks or HPAIV H5N1 surveillance

  13. Clinical Characteristics of 26 Human Cases of Highly Pathogenic Avian Influenza A (H5N1) Virus Infection in China

    PubMed Central

    Xiang, Nijuan; Zhou, Lei; Huai, Yang; Feng, Luzhao; Peng, Zhibin; Li, Zhongjie; Xu, Cuiling; Li, Junhua; Hu, Chengping; Li, Qun; Xu, Xiaoling; Liu, Xuecheng; Liu, Zigui; Xu, Longshan; Chen, Yusheng; Luo, Huiming; Wei, Liping; Zhang, Xianfeng; Xin, Jianbao; Guo, Junqiao; Wang, Qiuyue; Yuan, Zhengan; Zhou, Longnv; Zhang, Kunzhao; Zhang, Wei; Yang, Jinye; Zhong, Xiaoning; Xia, Shichang; Li, Lanjuan; Cheng, Jinquan; Ma, Erdang; He, Pingping; Lee, Shui Shan; Wang, Yu; Uyeki, Timothy M.; Yang, Weizhong

    2008-01-01

    Background While human cases of highly pathogenic avian influenza A (H5N1) virus infection continue to increase globally, available clinical data on H5N1 cases are limited. We conducted a retrospective study of 26 confirmed human H5N1 cases identified through surveillance in China from October 2005 through April 2008. Methodology/Principal Findings Data were collected from hospital medical records of H5N1 cases and analyzed. The median age was 29 years (range 6–62) and 58% were female. Many H5N1 cases reported fever (92%) and cough (58%) at illness onset, and had lower respiratory findings of tachypnea and dyspnea at admission. All cases progressed rapidly to bilateral pneumonia. Clinical complications included acute respiratory distress syndrome (ARDS, 81%), cardiac failure (50%), elevated aminotransaminases (43%), and renal dysfunction (17%). Fatal cases had a lower median nadir platelet count (64.5×109 cells/L vs 93.0×109 cells/L, p = 0.02), higher median peak lactic dehydrogenase (LDH) level (1982.5 U/L vs 1230.0 U/L, p = 0.001), higher percentage of ARDS (94% [n = 16] vs 56% [n = 5], p = 0.034) and more frequent cardiac failure (71% [n = 12] vs 11% [n = 1], p = 0.011) than nonfatal cases. A higher proportion of patients who received antiviral drugs survived compared to untreated (67% [8/12] vs 7% [1/14], p = 0.003). Conclusions/Significance The clinical course of Chinese H5N1 cases is characterized by fever and cough initially, with rapid progression to lower respiratory disease. Decreased platelet count, elevated LDH level, ARDS and cardiac failure were associated with fatal outcomes. Clinical management of H5N1 cases should be standardized in China to include early antiviral treatment for suspected H5N1 cases. PMID:18716658

  14. Spatial Distribution and Risk Factors of Highly Pathogenic Avian Influenza (HPAI) H5N1 in China

    PubMed Central

    Martin, Vincent; Pfeiffer, Dirk U.; Zhou, Xiaoyan; Xiao, Xiangming; Prosser, Diann J.; Guo, Fusheng; Gilbert, Marius

    2011-01-01

    Highly pathogenic avian influenza (HPAI) H5N1 was first encountered in 1996 in Guangdong province (China) and started spreading throughout Asia and the western Palearctic in 2004–2006. Compared to several other countries where the HPAI H5N1 distribution has been studied in some detail, little is known about the environmental correlates of the HPAI H5N1 distribution in China. HPAI H5N1 clinical disease outbreaks, and HPAI virus (HPAIV) H5N1 isolated from active risk-based surveillance sampling of domestic poultry (referred to as HPAIV H5N1 surveillance positives in this manuscript) were modeled separately using seven risk variables: chicken, domestic waterfowl population density, proportion of land covered by rice or surface water, cropping intensity, elevation, and human population density. We used bootstrapped logistic regression and boosted regression trees (BRT) with cross-validation to identify the weight of each variable, to assess the predictive power of the models, and to map the distribution of HPAI H5N1 risk. HPAI H5N1 clinical disease outbreak occurrence in domestic poultry was mainly associated with chicken density, human population density, and elevation. In contrast, HPAIV H5N1 infection identified by risk-based surveillance was associated with domestic waterfowl density, human population density, and the proportion of land covered by surface water. Both models had a high explanatory power (mean AUC ranging from 0.864 to 0.967). The map of HPAIV H5N1 risk distribution based on active surveillance data emphasized areas south of the Yangtze River, while the distribution of reported outbreak risk extended further North, where the density of poultry and humans is higher. We quantified the statistical association between HPAI H5N1 outbreak, HPAIV distribution and post-vaccination levels of seropositivity (percentage of effective post-vaccination seroconversion in vaccinated birds) and found that provinces with either outbreaks or HPAIV H5N1 surveillance

  15. Spatial modeling of wild bird risk factors to investigate highly pathogenic A(H5N1) avian influenza virus transmission

    USGS Publications Warehouse

    Prosser, Diann J.; Hungerford, Laura L.; Erwin, R. Michael; Ottinger, Mary Ann; Takekawa, John Y.; Newman, Scott H.; Xiao, Xianming; Ellis, Erie C.

    2016-01-01

    One of the longest-persisting avian influenza viruses in history, highly pathogenic avian influenza virus (HPAIV) A(H5N1), continues to evolve after 18 years, advancing the threat of a global pandemic. Wild waterfowl (family Anatidae), are reported as secondary transmitters of HPAIV, and primary reservoirs for low-pathogenic avian influenza viruses, yet spatial inputs for disease risk modeling for this group have been lacking. Using GIS and Monte Carlo simulations, we developed geospatial indices of waterfowl abundance at 1 and 30 km resolutions and for the breeding and wintering seasons for China, the epicenter of H5N1. Two spatial layers were developed: cumulative waterfowl abundance (WAB), a measure of predicted abundance across species, and cumulative abundance weighted by H5N1 prevalence (WPR), whereby abundance for each species was adjusted based on prevalence values then totaled across species. Spatial patterns of the model output differed between seasons, with higher WAB and WPR in the northern and western regions of China for the breeding season and in the southeast for the wintering season. Uncertainty measures indicated highest error in southeastern China for both WAB and WPR. We also explored the effect of resampling waterfowl layers from 1 km to 30 km resolution for multi-scale risk modeling. Results indicated low average difference (less than 0.16 and 0.01 standard deviations for WAB and WPR, respectively), with greatest differences in the north for the breeding season and southeast for the wintering season. This work provides the first geospatial models of waterfowl abundance available for China. The indices provide important inputs for modeling disease transmission risk at the interface of poultry and wild birds. These models are easily adaptable, have broad utility to both disease and conservation needs, and will be available to the scientific community for advanced modeling applications.

  16. Experimental challenge and pathology of highly pathogenic avian influenza virus H5N1 in dunlin (Calidris alpina), an intercontinental migrant shorebird species

    USGS Publications Warehouse

    Hall, J.S.; Franson, J.C.; Gill, R.E.; Meteyer, C.U.; Teslaa, J.L.; Nashold, S.; Dusek, R.J.; Ip, H.S.

    2011-01-01

    Background Shorebirds (Charadriiformes) are considered one of the primary reservoirs of avian influenza. Because these species are highly migratory, there is concern that infected shorebirds may be a mechanism by which highly pathogenic avian influenza virus (HPAIV) H5N1 could be introduced into North America from Asia. Large numbers of dunlin (Calidris alpina) migrate from wintering areas in central and eastern Asia, where HPAIV H5N1 is endemic, across the Bering Sea to breeding areas in Alaska. Low pathogenic avian influenza virus has been previously detected in dunlin, and thus, dunlin represent a potential risk to transport HPAIV to North America. To date no experimental challenge studies have been performed in shorebirds. Methods Wild dunlin were inoculated intranasally and intrachoanally various doses of HPAIV H5N1. The birds were monitored daily for virus excretion, disease signs, morbidity, and mortality. Results The infectious dose of HPAIV H5N1 in dunlin was determined to be 101.7 EID50/100 ??l and that the lethal dose was 101.83 EID50/100 ??l. Clinical signs were consistent with neurotropic disease, and histochemical analyses revealed that infection was systemic with viral antigen and RNA most consistently found in brain tissues. Infected birds excreted relatively large amounts of virus orally (104 EID50) and smaller amounts cloacally. Conclusions Dunlin are highly susceptible to infection with HPAIV H5N1. They become infected after exposure to relatively small doses of the virus and if they become infected, they are most likely to suffer mortality within 3-5days. These results have important implications regarding the risks of transport and transmission of HPAIV H5N1 to North America by this species and raises questions for further investigation. Published 2011. This article is a US Government work and is in the public domain in the USA.

  17. Movements of wild ruddy shelducks in the Central Asian Flyway and their spatial relationship to outbreaks of highly pathogenic avian influenza H5N1.

    PubMed

    Takekawa, John Y; Prosser, Diann J; Collins, Bridget M; Douglas, David C; Perry, William M; Yan, Baoping; Ze, Luo; Hou, Yuansheng; Lei, Fumin; Li, Tianxian; Li, Yongdong; Newman, Scott H

    2013-09-01

    Highly pathogenic avian influenza H5N1 remains a serious concern for both poultry and human health. Wild waterfowl are considered to be the reservoir for low pathogenic avian influenza viruses; however, relatively little is known about their movement ecology in regions where HPAI H5N1 outbreaks regularly occur. We studied movements of the ruddy shelduck (Tadorna ferruginea), a wild migratory waterfowl species that was infected in the 2005 Qinghai Lake outbreak. We defined their migration with Brownian Bridge utilization distribution models and their breeding and wintering grounds with fixed kernel home ranges. We correlated their movements with HPAI H5N1 outbreaks, poultry density, land cover, and latitude in the Central Asian Flyway. Our Akaike Information Criterion analysis indicated that outbreaks were correlated with land cover, latitude, and poultry density. Although shelduck movements were included in the top two models, they were not a top parameter selected in AICc stepwise regression results. However, timing of outbreaks suggested that outbreaks in the flyway began during the winter in poultry with spillover to wild birds during the spring migration. Thus, studies of the movement ecology of wild birds in areas with persistent HPAI H5N1 outbreaks may contribute to understanding their role in transmission of this disease. PMID:24022072

  18. High-yield production of a stable Vero cell-based vaccine candidate against the highly pathogenic avian influenza virus H5N1

    SciTech Connect

    Zhou, Fangye; Zhou, Jian; Ma, Lei; Song, Shaohui; Zhang, Xinwen; Li, Weidong; Jiang, Shude; Wang, Yue; Liao, Guoyang

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer Vero cell-based HPAI H5N1 vaccine with stable high yield. Black-Right-Pointing-Pointer Stable high yield derived from the YNVa H3N2 backbone. Black-Right-Pointing-Pointer H5N1/YNVa has a similar safety and immunogenicity to H5N1delta. -- Abstract: Highly pathogenic avian influenza (HPAI) viruses pose a global pandemic threat, for which rapid large-scale vaccine production technology is critical for prevention and control. Because chickens are highly susceptible to HPAI viruses, the supply of chicken embryos for vaccine production might be depleted during a virus outbreak. Therefore, developing HPAI virus vaccines using other technologies is critical. Meeting vaccine demand using the Vero cell-based fermentation process has been hindered by low stability and yield. In this study, a Vero cell-based HPAI H5N1 vaccine candidate (H5N1/YNVa) with stable high yield was achieved by reassortment of the Vero-adapted (Va) high growth A/Yunnan/1/2005(H3N2) (YNVa) virus with the A/Anhui/1/2005(H5N1) attenuated influenza vaccine strain (H5N1delta) using the 6/2 method. The reassorted H5N1/YNVa vaccine maintained a high hemagglutination (HA) titer of 1024. Furthermore, H5N1/YNVa displayed low pathogenicity and uniform immunogenicity compared to that of the parent virus.

  19. The enigma of the apparent disappearance of Eurasian highly pathogenic H5 clade 2.3.4.4 influenza A viruses in North American waterfowl.

    PubMed

    Krauss, Scott; Stallknecht, David E; Slemons, Richard D; Bowman, Andrew S; Poulson, Rebecca L; Nolting, Jacqueline M; Knowles, James P; Webster, Robert G

    2016-08-01

    One of the major unresolved questions in influenza A virus (IAV) ecology is exemplified by the apparent disappearance of highly pathogenic (HP) H5N1, H5N2, and H5N8 (H5Nx) viruses containing the Eurasian hemagglutinin 2.3.4.4 clade from wild bird populations in North America. The introduction of Eurasian lineage HP H5 clade 2.3.4.4 H5N8 IAV and subsequent reassortment with low-pathogenic H?N2 and H?N1 North American wild bird-origin IAVs in late 2014 resulted in widespread HP H5Nx IAV infections and outbreaks in poultry and wild birds across two-thirds of North America starting in November 2014 and continuing through June 2015. Although the stamping out strategies adopted by the poultry industry and animal health authorities in Canada and the United States-which included culling, quarantining, increased biosecurity, and abstention from vaccine use-were successful in eradicating the HP H5Nx viruses from poultry, these activities do not explain the apparent disappearance of these viruses from migratory waterfowl. Here we examine current and historical aquatic bird IAV surveillance and outbreaks of HP H5Nx in poultry in the United States and Canada, providing additional evidence of unresolved mechanisms that restrict the emergence and perpetuation of HP avian influenza viruses in these natural reservoirs. PMID:27457948

  20. Movements of wild ruddy shelducks in the Central Asian Flyway and their spatial relationship to outbreaks of highly pathogenic avian influenza H5N1

    USGS Publications Warehouse

    Takekawa, John Y.; Prosser, Diann J.; Collins, Bridget M.; Douglas, David C.; Perry, William M.; Baoping, Yan; Luo, Ze; Hou, Yuansheng; Lei, Fumin; Li, Tianxian; Li, Yongdong; Newman, Scott H.

    2013-01-01

    Highly pathogenic avian influenza H5N1 remains a serious concern for both poultry and human health. Wild waterfowl are considered to be the reservoir for low pathogenic avian influenza viruses; however, relatively little is known about their movement ecology in regions where HPAI H5N1 outbreaks regularly occur. We studied movements of the ruddy shelduck (Tadorna ferruginea), a wild migratory waterfowl species that was infected in the 2005 Qinghai Lake outbreak. We defined their migration with Brownian Bridge utilization distribution models and their breeding and wintering grounds with fixed kernel home ranges. We correlated their movements with HPAI H5N1 outbreaks, poultry density, land cover, and latitude in the Central Asian Flyway. Our Akaike Information Criterion analysis indicated that outbreaks were correlated with land cover, latitude, and poultry density. Although shelduck movements were included in the top two models, they were not a top parameter selected in AICc stepwise regression results. However, timing of outbreaks suggested that outbreaks in the flyway began during the winter in poultry with spillover to wild birds during the spring migration. Thus, studies of the movement ecology of wild birds in areas with persistent HPAI H5N1 outbreaks may contribute to understanding their role in transmission of this disease.

  1. Surveillance for high pathogenicity avian influenza virus in wild birds in the Pacific Flyway of the United States, 2006-2007

    USGS Publications Warehouse

    Dusek, R.J.; Bortner, J.B.; DeLiberto, T.J.; Hoskins, J.; Franson, J. Christian; Bales, B.D.; Yparraguirre, D.; Swafford, S.R.; Ip, H.S.

    2009-01-01

    In 2006 the U.S. Department of Agriculture, U.S. Department of Interior, and cooperating state fish and wildlife agencies began surveillance for high-pathogenicity avian influenza (HPAI) H5N1 virus in wild birds in the Pacific Flyway of the United States. This surveillance effort was highly integrated in California, Oregon, Washington, Idaho, Nevada, Arizona, Utah, and western Montana, with collection of samples coordinated with state agencies. Sampling focused on live wild birds, hunterkilled waterfowl during state hunting seasons, and wild bird mortality events. Of 20,888 samples collected, 18,139 were from order Anseriformes (waterfowl) and 2010 were from order Charadriiformes (shorebirds), representing the two groups of birds regarded to be the primary reservoirs of avian influenza viruses. Although 83 birds were positive by H5 real-time reverse transcription polymerase chain reaction (rRT-PCR), no HPAI H5N1 virus was found. Thirty-two virus isolates were obtained from the H5- positive samples, including low-pathogenicity H5 viruses identified as H5N2, H5N3, and H5N9.

  2. Pathogenesis and transmissibility of highly (H7N1) and low (H7N9) pathogenic avian influenza virus infection in red-legged partridge (Alectoris rufa)

    PubMed Central

    2011-01-01

    An experimental infection with highly pathogenic avian influenza virus (HPAIV) and low pathogenic avian influenza virus (LPAIV) was carried out in red-legged partridges (Alectoris rufa) in order to study clinical signs, gross and microscopic lesions, and viral distribution in tissues and viral shedding. Birds were infected with a HPAIV subtype H7N1 (A/Chicken/Italy/5093/1999) and a LPAIV subtype H7N9 (A/Anas crecca/Spain/1460/2008). Uninoculated birds were included as contacts in both groups. In HPAIV infected birds, the first clinical signs were observed at 3 dpi, and mortality started at 4 dpi, reaching 100% at 8 dpi. The presence of viral antigen in tissues and viral shedding were confirmed by immunohistochemistry and quantitative real time RT-PCR (qRRT-PCR), respectively, in all birds infected with HPAIV. However, neither clinical signs nor histopathological findings were observed in LPAIV infected partridges. In addition, only short-term viral shedding together with seroconversion was detected in some LPAIV inoculated animals. The present study demonstrates that the red-legged partridge is highly susceptible to the H7N1 HPAIV strain, causing severe disease, mortality and abundant viral shedding and thus contributing to the spread of a potential local outbreak of this virus. In contrast, our results concerning H7N9 LPAIV suggest that the red-legged partridge is not a reservoir species for this virus. PMID:21314907

  3. Movements of Wild Ruddy Shelducks in the Central Asian Flyway and Their Spatial Relationship to Outbreaks of Highly Pathogenic Avian Influenza H5N1

    PubMed Central

    Takekawa, John Y.; Prosser, Diann J.; Collins, Bridget M.; Douglas, David C.; Perry, William M.; Yan, Baoping; Ze, Luo; Hou, Yuansheng; Lei, Fumin; Li, Tianxian; Li, Yongdong; Newman, Scott H.

    2013-01-01

    Highly pathogenic avian influenza H5N1 remains a serious concern for both poultry and human health. Wild waterfowl are considered to be the reservoir for low pathogenic avian influenza viruses; however, relatively little is known about their movement ecology in regions where HPAI H5N1 outbreaks regularly occur. We studied movements of the ruddy shelduck (Tadorna ferruginea), a wild migratory waterfowl species that was infected in the 2005 Qinghai Lake outbreak. We defined their migration with Brownian Bridge utilization distribution models and their breeding and wintering grounds with fixed kernel home ranges. We correlated their movements with HPAI H5N1 outbreaks, poultry density, land cover, and latitude in the Central Asian Flyway. Our Akaike Information Criterion analysis indicated that outbreaks were correlated with land cover, latitude, and poultry density. Although shelduck movements were included in the top two models, they were not a top parameter selected in AICc stepwise regression results. However, timing of outbreaks suggested that outbreaks in the flyway began during the winter in poultry with spillover to wild birds during the spring migration. Thus, studies of the movement ecology of wild birds in areas with persistent HPAI H5N1 outbreaks may contribute to understanding their role in transmission of this disease. PMID:24022072

  4. Molecular Signatures Associated with Mx1-Mediated Resistance to Highly Pathogenic Influenza Virus Infection: Mechanisms of Survival

    PubMed Central

    Cilloniz, Cristian; Pantin-Jackwood, Mary J.; Ni, Chester; Carter, Victoria S.; Korth, Marcus J.; Swayne, David E.; Tumpey, Terrence M.

    2012-01-01

    Understanding the role of host factors during lethal influenza virus infection is critical to deciphering the events that 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 gene expression profiles in lung tissue from BALB/c (Mx1−) and BALB · A2G-Mx1 mice (Mx1+/+) infected with the fully reconstructed 1918 pandemic influenza virus. Mx1+/+ mice showed less tissue damage than Mx− animals, and pathology and mortality were further reduced by treating the mice with interferon prior to infection. Using global transcriptional profiling, we identified distinct molecular signatures associated with partial protection, complete protection, and the contribution of interferon to the host response. In the absence of interferon treatment, partial protection was characterized by the generation of an acute response with the upregulation of genes associated with apoptosis, reactive oxygen species, and cell migration. Complete protection was characterized by the downregulation of cytokine and chemokine genes previously associated with influenza virus pathogenesis. The contribution of interferon treatment to total protection in virus-infected Mx1+/+ mice was characterized by the altered regulation of cell cycle genes. These genes were upregulated in Mx1+/+ mice treated with interferon but downregulated in the absence of interferon treatment. Our results suggest that Mx1+/+ mice generate a protective antiviral response by controlling the expression of key modulator molecules associated with influenza virus lethality. PMID:22190720

  5. Avian Influenza.

    PubMed

    Zeitlin, Gary Adam; Maslow, Melanie Jane

    2005-05-01

    The current epidemic of H5N1 highly pathogenic avian influenza in Southeast Asia raises serious concerns that genetic reassortment will result in the next influenza pandemic. There have been 164 confirmed cases of human infection with avian influenza since 1996. In 2004, there were 45 cases of human H5N1 in Vietnam and Thailand, with a mortality rate more than 70%. In addition to the potential public health hazard, the current zoonotic epidemic has caused severe economic losses. Efforts must be concentrated on early detection of bird outbreaks with aggressive culling, quarantining, and disinfection. To prepare for and prevent an increase in human cases, it is essential to improve detection methods and stockpile effective antivirals. Novel therapeutic modalities, including short-interfering RNAs and new vaccine strategies that use plasmid-based genetic systems, offer promise should a pandemic occur. PMID:15847721

  6. Avian influenza.

    PubMed

    Zeitlin, Gary A; Maslow, Melanie J

    2006-03-01

    The current epidemic of H5N1 highly pathogenic avian influenza in Southeast Asia raises serious concerns that genetic reassortment will result in the next influenza pandemic. There have been 164 confirmed cases of human infection with avian influenza since 1996. In 2004 alone, there were 45 cases of human H5N1 in Vietnam and Thailand, with a mortality rate over 70%. In addition to the potential public health hazard, the current zoonotic epidemic has caused severe economic losses. Efforts must be concentrated on early detection of bird outbreaks with aggressive culling, quarantines, and disinfection. To prepare for and prevent increased human cases, it is essential to improve detection methods and stockpile effective antivirals. Novel therapeutic modalities, including short, interfering RNAs and new vaccine strategies that use plasmid-based genetic systems offer promise, should a pandemic occur. PMID:16566867

  7. Specific Residues of PB2 and PA Influenza Virus Polymerase Subunits Confer the Ability for RNA Polymerase II Degradation and Virus Pathogenicity in Mice

    PubMed Central

    Llompart, C. M.

    2014-01-01

    ABSTRACT Influenza virus transcription requires functional coupling with cellular transcription for the cap-snatching process. Despite this fact, RNA polymerase II (RNAP II) is degraded during infection in a process triggered by the viral polymerase. Reassortant viruses from the A/PR/8/34 (PR8) strain that induce (hvPR8) or do not induce (lvPR8) RNAP II degradation led to the identification of PA and PB2 subunits as responsible for the degradation process. Three changes in the PB2 sequence (I105M, N456D, and I504V) and two in PA (Q193H and I550L) differentiate PA and PB2 of lvPR8 from those of hvPR8. Using recombinant viruses, we observed that changes at position 504 of PB2, together with 550 of PA, confer the ability on lvPR8 for RNAP II degradation and, conversely, abolish hvPR8 degradation capacity. Since hvPR8 is more pathogenic than lvPR8 in mice, we tested the potential contribution of RNAP II degradation in a distant viral strain, the 2009 pandemic A/California/04/09 (CAL) virus, whose PA and PB2 subunits are of avian origin. As in the hvPR8 virus, mutations at positions 504 of PB2 and 550 of PA in CAL virus abolished its RNAP II degradation capacity. Moreover, in an in vivo model, the CAL-infected mice lost more body weight, and 75% lethality was observed in this situation compared with 100% survival in mutant-CAL- or mock-infected animals. These results confirm the involvement of specific PB2 and PA residues in RNAP II degradation, which correlates with pathogenicity in mice of viruses containing human or avian polymerase PB2 and PA subunits. IMPORTANCE The influenza virus polymerase induces the degradation of RNAP II, which probably cooperates to avoid the antiviral response. Here, we have characterized two specific residues located in the PA and PB2 polymerase subunits that mediate this degradation in different influenza viruses. Moreover, a clear correlation between RNAP II degradation and in vivo pathogenicity in mice was observed, indicating that the

  8. New Carbocyclic Amino Acid Derivatives Inhibit Infection Caused by Highly Pathogenic Influenza A Virus Strain (H5N1).

    PubMed

    Shibnev, V A; Garaev, T M; Deryabin, P G; Finogenova, M P; Botikov, A G; Mishin, D V

    2016-06-01

    New amino acid derivatives with carbocycles of adamantine and quinaldic acid were synthesized and their in vitro antiviral activity against influenza A/H5N1 virus was evaluated. Experiments on cultured embryonic porcine kidney epithelial cells showed that amino acid derivatives suppressed viral replication. Tret-butyloxycarbonyl-DL-methionylsulfonyl-1-adamantayl ethylamine and benzyloxycarbonyl-L-trypthophanyl-1-adamantayl ethylamine compounds demonstrated high activity in all in vitro experiments. Moreover, some compounds showed virucidal activity against influenza A/H5N1 virus. PMID:27383164

  9. Pathogenicity and Transmissibility of Novel Reassortant H3N2 Influenza Viruses with 2009 Pandemic H1N1 Genes in Pigs

    PubMed Central

    Ma, Jingjiao; Shen, Huigang; Liu, Qinfang; Bawa, Bhupinder; Qi, Wenbao; Duff, Michael; Lang, Yuekun; Lee, Jinhwa; Yu, Hai; Bai, Jianfa; Tong, Guangzhi; Hesse, Richard A.; Richt, Jürgen A.

    2014-01-01

    ABSTRACT At least 10 different genotypes of novel reassortant H3N2 influenza viruses with 2009 pandemic H1N1 [A(H1N1)pdm09] gene(s) have been identified in U.S. pigs, including the H3N2 variant with a single A(H1N1)pdm09 M gene, which has infected more than 300 people. To date, only three genotypes of these viruses have been evaluated in animal models, and the pathogenicity and transmissibility of the other seven genotype viruses remain unknown. Here, we show that three H3N2 reassortant viruses that contain 3 (NP, M, and NS) or 5 (PA, PB2, NP, M, and NS) genes from A(H1N1)pdm09 were pathogenic in pigs, similar to the endemic H3N2 swine virus. However, the reassortant H3N2 virus with 3 A(H1N1)pdm09 genes and a recent human influenza virus N2 gene was transmitted most efficiently among pigs, whereas the reassortant H3N2 virus with 5 A(H1N1)pdm09 genes was transmitted less efficiently than the endemic H3N2 virus. Interestingly, the polymerase complex of reassortant H3N2 virus with 5 A(H1N1)pdm09 genes showed significantly higher polymerase activity than those of endemic and reassortant H3N2 viruses with 3 A(H1N1)pdm09 genes. Further studies showed that an avian-like glycine at position 228 at the hemagglutinin (HA) receptor binding site is responsible for inefficient transmission of the reassortant H3N2 virus with 5 A(H1N1)pdm09 genes. Taken together, our results provide insights into the pathogenicity and transmissibility of novel reassortant H3N2 viruses in pigs and suggest that a mammalian-like serine at position 228 in the HA is critical for the transmissibility of these reassortant H3N2 viruses. IMPORTANCE Swine influenza is a highly contagious zoonotic disease that threatens animal and public health. Introduction of 2009 pandemic H1N1 virus [A(H1N1)pdm09] into swine herds has resulted in novel reassortant influenza viruses in swine, including H3N2 and H1N2 variants that have caused human infections in the United States. We showed that reassortant H3N2 influenza

  10. DIVA vaccination strategies for avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vaccination for both low pathogenic and highly pathogenic avian influenza is commonly used for countries that have been endemic for avian influenza influenza virus, but stamping out policies are common for countries that are normally free of the disease. Stamping out policies of euthanizing infecte...

  11. Cytomegalovirus: the stealth virus.

    PubMed

    Robinson, Sharon

    2016-05-01

    Cytomegalovirus (CMV) is an infection, part of the herpes family of viruses which, if contracted during pregnancy, cancause devastating effects on the newborn baby. This article is written by the trustee of a volunteer-based charity, mostly run by mothers of CMV children, who are striving to raise awareness of this infection, which is more common than Down's syndrome, listeria and toxoplasmosis, and is theprimary preventable cause of childhood hearing loss. PMID:27295757

  12. 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...

  13. 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 ...

  14. Experimental co-infection of SPF chickens with low pathogenicity avian influenza virus (LPAIV) subtypes H9N2, H5N2 and H7N9, and infectious bronchitis virus (IBV)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza virus (AIV) and infectious bronchitis virus (IBV) are two of the most important respiratory viruses affecting poultry worldwide, but little is known about the effect of co-infection of these two viruses in poultry. Low pathogenicity (LP) AIV can produce from mild to moderate upper r...

  15. Evaluation of the U.S. Department of Agriculture's egg pasteurization processes on the inactivation of high pathogenicity avian influenza virus and velogenic Newcastle disease virus in processed egg products

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High pathogenicity avian influenza virus (HPAIV) A/chicken/Pennsylvania/1370/1983 (H5N2), and velogenic Newcastle disease virus (vNDV) AMPV-1/California/212676/2002 were inoculated into various egg products then heat treated at various temperatures for 0 to 30 min to determine thermal inactivation p...

  16. Phylogenetic analysis of hemagglutinin and neuraminidase genes of highly pathogenic avian influenza H5N1 Egyptian strains isolated from 2006 to 2008 indicates heterogeneity with multiple distinct sublineages

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Eurasian lineage H5N1 Highly pathogenic avian influenza (HPAI) virus caused widespread outbreaks in Egypt in 2006 and eventually become enzootic in poultry. Although outbreaks have a seasonal pattern with most occurring during the cooler winter months, it remains unclear if this seasonality ref...

  17. Variation in protection of four divergent avian influenza virus vaccine seed strains against eight clade 2.2.1 and 2.2.1.1. Egyptian H5N1 high pathogenicity variants in poultry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Highly pathogenic (HP) H5N1 avian influenza virus (AIV) was introduced to Egyptian poultry in 2006 and has since become enzootic. Vaccination has been utilized as a control tool, but for a variety of reasons the disease has not been eradicated. In 2007, an antigenically divergent hemagglutinin sub-c...

  18. Antibody titer has positive predictive value for vaccine protection against challenge with natural antigenic-drift variants of H5N1 high-pathogenicity avian influenza viruses from Indonesia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Beginning with Hong Kong in 2002, vaccines have been used as part of an integrated control strategy in 14 countries/regions to protect poultry against H5N1 high pathogenicity avian influenza (HPAI). H5N1 HPAI was first reported in Indonesia in 2003 and vaccination was initiated the following year. ...

  19. Comparative efficacy of North American and antigenically matched reverse genetics derived H5N9 DIVA marker vaccines against highly pathogenic Asian H5N1 avian influenza in chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Highly pathogenic (HP) H5N1 avian influenza has become endemic in several countries in Asia and Africa, and vaccination is being widely used as a control tool. However, there is a need for efficacious vaccines preferably utilizing a DIVA (differentiate infected from vaccinated animals) marker strat...

  20. Efficacy of a recombinant turkey herpesvirus H5 vaccine against challenge with H5N1 clades 1.1.2 and 2.3.2.1 highly pathogenic avian influenza viruses in domestic ducks (Anas platyrhynchos domesticus)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Goose/Guangdong (Gs/GD)-lineage H5N1 highly pathogenic avian influenza (HPAI) viruses continue to circulate and cause great economic losses in poultry in Asia, the Middle East, and Africa. Recently, the Gs/GD-lineage H5N8 HPAI virus belonging to clade 2.3.4.4 and its reassortants have caused out...

  1. Transmission of H5N1 high pathogenicity avian influenza virus to Herring gulls (Larus argentatus) through intranasal inoculation of virus and ingestion of virus-infected chicken meat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In order to evaluate the susceptibility of herring gulls (Larus argentatus) to H5N1 highly pathogenic avian influenza (HPAI) virus under natural routes of infection, we exposed gulls to two Asian lineage H5N1 HPAI viruses (A/whooper swan/Mongolia/244/05 and A/duck meat/Anyang/AVL-1/01) via intranasa...

  2. 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...

  3. 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...

  4. Inactivation of low pathogenicity notifiable avian influenza virus and lentogenic Newcastle disease virus following pasteurization in liquid egg products

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sixty seven million cases of shell eggs produced per year in the U.S. are processed as liquid egg product. The U.S. also exports a large amount of egg products. Although the U.S. is normally free of avian influenza, concern about contamination of egg product with these viruses has in the past result...

  5. Highly (H5N1) and low (H7N2) pathogenic avian influenza virus infection in falcons via nasochoanal route and ingestion of experimentally infected prey.

    PubMed

    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 and

  6. Satellite Tracking on the Flyways of Brown-Headed Gulls and Their Potential Role in the Spread of Highly Pathogenic Avian Influenza H5N1 Virus

    PubMed Central

    Ratanakorn, Parntep; Wiratsudakul, Anuwat; Wiriyarat, Witthawat; Eiamampai, Krairat; Farmer, Adrian H.; Webster, Robert G.; Chaichoune, Kridsada; Suwanpakdee, Sarin; Pothieng, Duangrat; Puthavathana, Pilaipan

    2012-01-01

    Brown-headed gulls (Larus brunnicephalus), winter visitors of Thailand, were tracked by satellite telemetry during 2008–2011 for investigating their roles in the highly pathogenic avian influenza (HPAI) H5N1 virus spread. Eight gulls negative for influenza virus infection were marked with solar-powered satellite platform transmitters at Bang Poo study site in Samut Prakarn province, Thailand; their movements were monitored by the Argos satellite tracking system, and locations were mapped. Five gulls completed their migratory cycles, which spanned 7 countries (China, Bangladesh, India, Myanmar, Thailand, Cambodia, and Vietnam) affected by the HPAI H5N1 virus. Gulls migrated from their breeding grounds in China to stay overwinter in Thailand and Cambodia; while Bangladesh, India, Myanmar, and Vietnam were the places of stopovers during migration. Gulls traveled an average distance of about 2400 km between Thailand and China and spent 1–2 weeks on migration. Although AI surveillance among gulls was conducted at the study site, no AI virus was isolated and no H5N1 viral genome or specific antibody was detected in the 75 gulls tested, but 6.6% of blood samples were positive for pan-influenza A antibody. No AI outbreaks were reported in areas along flyways of gulls in Thailand during the study period. Distance and duration of migration, tolerability of the captive gulls to survive the HPAI H5N1 virus challenge and days at viral shedding after the virus challenging suggested that the Brown-headed gull could be a potential species for AI spread, especially among Southeast Asian countries, the epicenter of H5N1 AI outbreak. PMID:23209623

  7. Range-wide genetic population structure of common pochard (Aythya ferina): a potentially important vector of highly pathogenic avian influenza viruses

    PubMed Central

    Liu, Yang; Keller, Irene; Heckel, Gerald

    2011-01-01

    An understanding of the distribution and spatial structure of the natural vectors of zoonothic pathogens is of interest for effective disease control and prevention. Here, we investigate the range-wide population genetic structure of common pochard (Aythya ferina), a long-distance migratory duck and potential vector of highly pathogenic avian influenza. We collected several hundred samples from breeding and wintering grounds across Eurasia including some H5N1-positive individuals and generated partial sequences of the mitochondrial control region and multilocus microsatellite genotypes. Genetic differentiation among breeding populations was significant for both marker types but higher for maternally inherited mtDNA than for biparentally inherited nuclear markers. There was only weak genetic divergence between ducks sampled in Europe and East Asia, and genetic differentiation between populations was not generally associated with geographical distance. No evidence of genetic substructure was detected for ducks sampled on the European wintering grounds. Our results suggest limited breeding-site fidelity, especially in females, but extensive population admixture on the wintering grounds. The specific role of pochards as natural vectors of zoonotic pathogens and in particular H5N1 remains to be clarified but our results point to wintering grounds as potential hotspots for disease transmission. PMID:22393520

  8. Range-wide genetic population structure of common pochard (Aythya ferina): a potentially important vector of highly pathogenic avian influenza viruses.

    PubMed

    Liu, Yang; Keller, Irene; Heckel, Gerald

    2011-12-01

    An understanding of the distribution and spatial structure of the natural vectors of zoonothic pathogens is of interest for effective disease control and prevention. Here, we investigate the range-wide population genetic structure of common pochard (Aythya ferina), a long-distance migratory duck and potential vector of highly pathogenic avian influenza. We collected several hundred samples from breeding and wintering grounds across Eurasia including some H5N1-positive individuals and generated partial sequences of the mitochondrial control region and multilocus microsatellite genotypes. Genetic differentiation among breeding populations was significant for both marker types but higher for maternally inherited mtDNA than for biparentally inherited nuclear markers. There was only weak genetic divergence between ducks sampled in Europe and East Asia, and genetic differentiation between populations was not generally associated with geographical distance. No evidence of genetic substructure was detected for ducks sampled on the European wintering grounds. Our results suggest limited breeding-site fidelity, especially in females, but extensive population admixture on the wintering grounds. The specific role of pochards as natural vectors of zoonotic pathogens and in particular H5N1 remains to be clarified but our results point to wintering grounds as potential hotspots for disease transmission. PMID:22393520

  9. Transcription factor regulation and cytokine expression following in vitro infection of primary chicken cell culture with low pathogenic avian influenza virus

    PubMed Central

    2013-01-01

    Background Avian influenza virus (AIV) induced proinflammatory cytokine expression is believed to contribute to the disease pathogenesis following infection of poultry. However, there is limited information on the avian immune response to infection with low pathogenic avian influenza virus (LPAIV). Methods To gain a better understanding of the early viral-host interactions of LPAIV in chickens, primary chicken embryo hepatocytes (CEH) were infected with four different LPAIVs of U.S. origin. Kinetics of virus replication, transcription factor (c-Jun, p50 and IRF-3) activation and immune response gene (IL-6, IL-1beta, IFN-alpha and Mx) expression were studied at four different time points (6, 12, 24 and 48 hours) post infection and compared to non-infected controls. Results CEH can support growth of the tested LPAIVs when with trypsin supplementation. All four immune response genes tested were upregulated following infection as were transcription factors c-Jun, p50 and IRF-3. Amplification of these genes was dependant on virus replication (e.g. inclusion of trypsin), such that immune response genes and transcription factors were upregulated as viral titers increased. Conclusion The results of these studies demonstrate the requirement of virus replication for innate immune regulation and broaden our understanding of transcription factor responses related to LPAIV infection in chickens. PMID:24252391

  10. Intranasal immunization with live recombinant Lactococcus lactis combined with heat-labile toxin B subunit protects chickens from highly pathogenic avian influenza H5N1 virus.

    PubMed

    Lei, Han; Peng, Xiaojue; Shu, Handing; Zhao, Daxian

    2015-01-01

    Development of safe and effective vaccines to prevent highly pathogenic avian influenza H5N1 virus infection is a challenging goal. Lactococcus lactis (L. lactis) is an ideal delivery vector for vaccine development, and it has been shown previously that oral immunization of encapsulated secretory L. lactis-hemagglutinin (HA) could provide complete protection against homologous H5N1 virus challenge in the mice model. While intranasal immunization is an appealing approach, it is now reported that secretory L. lactis-HA combined with mucosal adjuvant heat-labile toxin B subunit (LTB) could provide protective immunity in the chicken model. As compared to intranasal immunization with L. lactis-HA alone, L. lactis-HA combined with LTB (L. lactis-HA + LTB) could elicit robust neutralizing antibody responses and mucosal IgA responses, as well as strong cellular immune responses in the vaccinated chickens. Importantly, intranasal immunization with L. lactis-HA + LTB could provide 100% protection against H5N1 virus challenge. Taken together, these results suggest that intranasal immunization with L. lactis-HA + LTB can be considered as an effective approach for preventing and controlling infection of H5N1 virus in poultry during an avian influenza A/H5N1 pandemic. PMID:24861477

  11. [DNA vaccination via in vivo electroporation can elicit specific immune response against highly pathogenic H5N1 influenza viral structural antigens in mice].

    PubMed

    Wang, Wen; Chen, Hong; Tan, Wen-jie; Deng, Yao; Wang, Min; Liu, Yuan; Yin, Xiao; Zhang, Ke; Guan, Jie; Zhou, Jian-fang; Shu, Yue-long; Ruan, Li

    2010-05-01

    This study aims to develop inexpensive and effective experimental vaccines against highly pathogenic H5N1 Avian Influenza (HPAI) virus and to optimize their immunization programs. To this end, we first synthesized the codon-optimized hemagglutinin gene (HAop) and neuraminidase gene (NAop), both of which were derived from a H5N1 virus (Anhui strain), and constructed successfully the DNA vaccines containing a single cistronic construct (HAwt, HAop, or NAop) or a bicistronic construct (HAop/M2 or NAop/M1) of H5N1 influenza virus origin. Their expression was confirmed by indirect immunofluorescent assay (IFA) and Western blotting. Then twice vaccination of mice with the DNA vaccines by injection intramuscularly or in vivo electroporation (EP) via two different routes was evaluated and analyzed by hemagglutination inhibition (HI) assay, NA-specific antibody detection, micro-neutralizing antibody test and IFN-gamma ELISpot assay. Our results showed that the DNA vaccines with coden-optimized HAop and NAop constructs could quickly elicit a strong immune response by in vivo EP, especially the cellular immune response against HA and NA; the in vivo EP via intradermal route induced stronger humoral immune responses than those via intramuscular route. Our findings will pave a way for further development of novel DNA-based H5N1 vaccine and for the optimization of the immunization programs of DNA vaccine. PMID:20572336

  12. Chances and Limitations of Wild Bird Monitoring for the Avian Influenza Virus H5N1 — Detection of Pathogens Highly Mobile in Time and Space

    PubMed Central

    Wilking, Hendrik; Ziller, Mario; Staubach, Christoph; Globig, Anja; Harder, Timm C.; Conraths, Franz J.

    2009-01-01

    Highly pathogenic influenza virus (HPAIV) H5N1 proved to be remarkably mobile in migratory bird populations where it has led to extensive outbreaks for which the true number of affected birds usually cannot be determined. For the evaluation of avian influenza monitoring and HPAIV early warning systems, we propose a time-series analysis that includes the estimation of confidence intervals for (i) the prevalence in outbreak situations or (ii) in the apparent absence of disease in time intervals for specified regional units. For the German outbreak regions in 2006 and 2007, the upper 95% confidence limit allowed the detection of prevalences below 1% only for certain time intervals. Although more than 25,000 birds were sampled in Germany per year, the upper 95% confidence limit did not fall below 5% in the outbreak regions for most of the time. The proposed analysis can be used to monitor water bodies and high risk areas, also as part of an early-warning system. Chances for an improved targeting of the monitoring system as part of a risk-based approach are discussed with the perspective of reducing sample sizes. PMID:19680560

  13. Outbreak of H5N2 highly pathogenic avian Influenza A virus infection in two commercial layer facilities: lesions and viral antigen distribution.

    PubMed

    Arruda, Paulo H E; Stevenson, Gregory W; Killian, Mary L; Burrough, Eric R; Gauger, Phillip C; Harmon, Karen M; Magstadt, Drew R; Yoon, Kyoung-Jin; Zhang, Jianqiang; Madson, Darin M; Piñeyro, Pablo; Derscheid, Rachel J; Schwartz, Kent J; Cooper, Vickie L; Halbur, Patrick G; Main, Rodger G; Sato, Yuko; Arruda, Bailey L

    2016-09-01

    The largest outbreak of highly pathogenic avian Influenza A virus (HPAIV) infection in U.S. history began in December 2014 resulting in the euthanasia of millions of birds and collateral economic consequences to the U.S. poultry industry. We describe 2 cases of H5N2 HPAIV infection in laying hens in Iowa. Following a sharp increase in mortality with minimal clinical signs, 15 dead birds, from 2 unrelated farms, were submitted to the Iowa State University Veterinary Diagnostic Laboratory. Common lesions included diffuse edema and multifocal hemorrhage of the comb, catarrhal exudate in the oropharynx, and multifocal tracheal hemorrhage. Less common lesions included epicardial petechiae, splenic hemorrhage, and pancreatic necrosis. Influenza A virus nucleoprotein was detected by immunohistochemistry in multiple cell types including ependymal cells, the choroid plexus, neurons, respiratory epithelium and macrophages in the lung, cardiac myocytes, endothelial cells, necrotic foci in the spleen, Kupffer cells in the liver, and necrotic acinar cells in the pancreas. Real-time polymerase chain reaction and sequencing confirmed H5N2 HPAIV with molecular characteristics similar to other contemporary U.S. H5N2 HPAIVs in both cases. PMID:27423731

  14. In vitro responses of chicken macrophage-like monocytes following exposure to pathogenic and non-pathogenic E. coli ghosts loaded with a rational design of conserved genetic materials of influenza and Newcastle disease viruses.

    PubMed

    Lagzian, Milad; Bassami, Mohammad Reza; Dehghani, Hesam

    2016-08-01

    Avian influenza virus (AIV) and Newcastle disease virus (NDV) are two important viral diseases in the poultry industry. Therefore, new disease-fighting strategies, especially effective genetic vaccination, are in high demand. Bacterial Ghost (BG) is a promising platform for delivering genetic materials to macrophages, cells that are among the first to encounter these viruses. However, there is no investigation on the immune response of these macrophage-targeted treatments. Here, we investigated the effect of genetic materials of AIV and NDV on the gene expression profile of important pro-inflammatory cytokines, a chemokine, a transcription factor, major histocompatibility complexes, and the viability of the chicken macrophage-like monocyte cells (CMM). Our genetic construct contained the external domain of matrix protein 2 and nucleoprotein gene of AIV, and immunodominant epitopes of fusion and hemagglutinin-neuraminidase proteins of NDV (hereinafter referred to as pAIV-Vax), delivered via the pathogenic and non-pathogenic BGs (Escherichia coli O78K80 and E. coli TOP10 respectively). The results demonstrated that both types of BGs were able to efficiently deliver the construct to the CMM, although the pathogenic strain derived BG was a significantly better stimulant and delivery vehicle. Both BGs were safe regarding LPS toxicity and did not induce any cell death. Furthermore, the loaded BGs were more powerful in modulating the pro-inflammatory cytokines' responses and antigen presentation systems in comparison to the unloaded BGs. Nitric oxide production of the BG-stimulated cells was also comparable to those challenged by the live bacteria. According to the results, the combination of pAIV-Vax construct and E. coli O78K80 BG is promising in inducing a considerable innate and adaptive immune response against AIV-NDV and perhaps the pathogenic E. coli, provided that the current combination be a potential candidate for in vivo testing regarding the development of an

  15. Cytomegalovirus Immunoglobulin After Thoracic Transplantation

    PubMed Central

    Grossi, Paolo; Mohacsi, Paul; Szabolcs, Zoltán; Potena, Luciano

    2016-01-01

    Abstract Cytomegalovirus (CMV) is a highly complex pathogen which, despite modern prophylactic regimens, continues to affect a high proportion of thoracic organ transplant recipients. The symptomatic manifestations of CMV infection are compounded by adverse indirect effects induced by the multiple immunomodulatory actions of CMV. These include a higher risk of acute rejection, cardiac allograft vasculopathy after heart transplantation, and potentially bronchiolitis obliterans syndrome in lung transplant recipients, with a greater propensity for opportunistic secondary infections. Prophylaxis for CMV using antiviral agents (typically oral valganciclovir or intravenous ganciclovir) is now almost universal, at least in high-risk transplants (D+/R−). Even with extended prophylactic regimens, however, challenges remain. The CMV events can still occur despite antiviral prophylaxis, including late-onset infection or recurrent disease, and patients with ganciclovir-resistant CMV infection or who are intolerant to antiviral therapy require alternative strategies. The CMV immunoglobulin (CMVIG) and antiviral agents have complementary modes of action. High-titer CMVIG preparations provide passive CMV-specific immunity but also exert complex immunomodulatory properties which augment the antiviral effect of antiviral agents and offer the potential to suppress the indirect effects of CMV infection. This supplement discusses the available data concerning the immunological and clinical effects of CMVIG after heart or lung transplantation. PMID:26900989

  16. An overview of the epidemic of highly pathogenic H5N1 avian influenza virus in Egypt: epidemiology and control challenges.

    PubMed

    Abdelwhab, E M; Hafez, H M

    2011-05-01

    Emergence of the highly pathogenic avian influenza (HPAI) H5N1 virus in Egypt in mid-February 2006 caused significant losses for the poultry industry and constituted a potential threat to public health. Since late 2007, there has been increasing evidence that stable lineages of H5N1 viruses are being established in chickens and humans in Egypt. The virus has been detected in wild, feral and zoo birds and recently was found in donkeys and pigs. Most of the outbreaks in poultry and humans occurred in the highly populated Nile delta. The temporal pattern of the virus has changed since 2009 with outbreaks now occurring in the warmer months of the year. Challenges to control of endemic disease in Egypt are discussed. For the foreseeable future, unless a global collaboration exists, HPAI H5N1 virus in Egypt will continue to compromise the poultry industry, endanger public health and pose a serious pandemic threat. PMID:21281550

  17. Cytomegalovirus Colitis in a Burn Patient.

    PubMed

    Gibbs, Jeff T; Zieger, Madeline; Sood, Rajiv

    2016-01-01

    The prevalence of cytomegalovirus in the burn population is high. However, its role in the clinical management of burn patients is still being defined. This report documents a 41-year-old man who developed cytomegalovirus (CMV) colitis after being admitted with a 72% burn. Before the administration of ganciclovir, the authors had difficulty controlling his quantitative wound cultures with serial debridements, topical agents, and systemic antibiotics for known pathogens, which led to graft loss. After the ganciclovir was given, his quantitative wound cultures improved without changing the authors' topical agents or systemic antibiotics and had improved graft take. Whether CMV infection alone contributed to an increased morbidity in this patient or the combination of bacteria/fungal infection with CMV led to a synergistic effect is still not clearly understood. CMV may have contributed to a dysfunction in his cell mediated immunity, which, in turn, lowered the bacterial and fungal load necessary to cause graft loss. Patients who continue to do poorly despite adequate treatment for known pathogens may need to be screened for CMV and treated. PMID:26056763

  18. Newcastle Disease Virus-Vectored Vaccines Expressing the Hemagglutinin or Neuraminidase Protein of H5N1 Highly Pathogenic Avian Influenza Virus Protect against Virus Challenge in Monkeys▿

    PubMed Central

    DiNapoli, Joshua M.; Nayak, Baibaswata; Yang, Lijuan; Finneyfrock, Brad W.; Cook, Anthony; Andersen, Hanne; Torres-Velez, Fernando; Murphy, Brian R.; Samal, Siba K.; Collins, Peter L.; Bukreyev, Alexander

    2010-01-01

    H5N1 highly pathogenic avian influenza virus (HPAIV) causes periodic outbreaks in humans, resulting in severe infections with a high (60%) incidence of mortality. The circulating strains have low human-to-human transmissibility; however, widespread concerns exist that enhanced transmission due to mutations could lead to a global pandemic. We previously engineered Newcastle disease virus (NDV), an avian paramyxovirus, as a vector to express the HPAIV hemagglutinin (HA) protein, and we showed that this vaccine (NDV/HA) induced a high level of HPAIV-specific mucosal and serum antibodies in primates when administered through the respiratory tract. Here we developed additional NDV-vectored vaccines expressing either HPAIV HA in which the polybasic cleavage site was replaced with that from a low-pathogenicity strain of influenza virus [HA(RV)], in order to address concerns of enhanced vector replication or genetic exchange, or HPAIV neuraminidase (NA). The three vaccine viruses [NDV/HA, NDV/HA(RV), and NDV/NA] were administered separately to groups of African green monkeys by the intranasal/intratracheal route. An additional group of animals received NDV/HA by aerosol administration. Each of the vaccine constructs was highly restricted for replication, with only low levels of virus shedding detected in respiratory secretions. All groups developed high levels of neutralizing antibodies against homologous and heterologous strains of HPAIV and were protected against challenge with 2 × 107 PFU of homologous HPAIV. Thus, needle-free, highly attenuated NDV-vectored vaccines expressing either HPAIV HA, HA(RV), or NA have been developed and demonstrated to be individually immunogenic and protective in a primate model of HPAIV infection. The finding that HA(RV) was protective indicates that it would be preferred for inclusion in a vaccine. The study also identified NA as an independent protective HPAIV antigen in primates. Furthermore, we demonstrated the feasibility of aerosol

  19. The Detection of a Low Pathogenicity Avian Influenza Virus Subtype H9 Infection in a Turkey Breeder Flock in the United Kingdom.

    PubMed

    Reid, Scott M; Banks, Jill; Ceeraz, Vanessa; Seekings, Amanda; Howard, Wendy A; Puranik, Anita; Collins, Susan; Manvell, Ruth; Irvine, Richard M; Brown, Ian H

    2016-05-01

    In April 2013, an H9N2 low pathogenicity avian influenza (LPAI) virus was isolated in a turkey breeder farm in Eastern England comprising 4966 birds. Point-of-lay turkey breeding birds had been moved from a rearing site and within 5 days had shown rapid onset of clinical signs of dullness, coughing, and anorexia. Three houses were involved, two contained a total of 4727 turkey hens, and the third housed 239 male turkeys. Around 50% of the hens were affected, whereas the male turkeys demonstrated milder clinical signs. Bird morbidity rose from 10% to 90%, with an increase in mortality in both houses of turkey hens to 17 dead birds in one house and 27 birds in the second house by day 6. The birds were treated with an antibiotic but were not responsive. Postmortem investigation revealed air sacculitis but no infraorbital sinus swellings or sinusitis. Standard samples were collected, and influenza A was detected. H9 virus infection was confirmed in all three houses by detection and subtyping of hemagglutinating agents in embryonated specific-pathogen-free fowls' eggs, which were shown to be viruses of H9N2 subtype using neuraminidase inhibition tests and a suite of real-time reverse transcription PCR assays. LPAI virus pathotype was suggested by cleavage site sequencing, and an intravenous pathogenicity index of 0.00 confirmed that the virus was of low pathogenicity. Therefore, no official disease control measures were required, and despite the high morbidity, birds recovered and were kept in production. Neuraminidase sequence analysis revealed a deletion of 78 nucleotides in the stalk region, suggesting an adaptation of the virus to poultry. Hemagglutinin gene sequences of two of the isolates clustered with a group of H9 viruses containing other contemporary European H9 strains in the Y439/Korean-like group. The closest matches to the two isolates were A/turkey/Netherlands/11015452/11 (H9N2; 97.9-98% nucleotide identity) and A/mallard/Finland/Li13384/10 (H9N2; 97

  20. Valvular Cytomegalovirus Endocarditis.

    PubMed

    Stear, Timothy J; Shersher, David; Kim, George J; Smego, Douglas R

    2016-08-01

    Endocarditis is a rare presentation for cytomegalovirus (CMV) infection. We present the case of a 49-year-old man who underwent mitral and tricuspid valve replacement for valvular CMV endocarditis. The patient's past medical history was significant for human immunodeficiency virus, intravenous drug abuse, and chronic hepatitis B. During his clinical course, he was found to have tricuspid and mitral valve vegetations. After progressive valvular destruction despite antibiotic therapy, he underwent successful mitral and tricuspid valve replacement. Pathologic analysis of the culture-negative valve specimens were found to contain inclusion bodies consistent with CMV, and quantitative serum polymerase chain reaction returned a highly elevated CMV DNA count. PMID:27449440

  1. Protective Efficacy of Newcastle Disease Virus Expressing Soluble Trimeric Hemagglutinin against Highly Pathogenic H5N1 Influenza in Chickens and Mice

    PubMed Central

    Cornelissen, Lisette A. H. M.; de Leeuw, Olav S.; Tacken, Mirriam G.; Klos, Heleen C.; de Vries, Robert P.; de Boer-Luijtze, Els A.; van Zoelen-Bos, Diana J.; Rigter, Alan; Rottier, Peter J. M.; Moormann, Rob J. M.; de Haan, Cornelis A. M.

    2012-01-01

    Background Highly pathogenic avian influenza virus (HPAIV) causes a highly contagious often fatal disease in poultry, resulting in significant economic losses in the poultry industry. HPAIV H5N1 also poses a major public health threat as it can be transmitted directly from infected poultry to humans. One effective way to combat avian influenza with pandemic potential is through the vaccination of poultry. Several live vaccines based on attenuated Newcastle disease virus (NDV) that express influenza hemagglutinin (HA) have been developed to protect chickens or mammalian species against HPAIV. However, the zoonotic potential of NDV raises safety concerns regarding the use of live NDV recombinants, as the incorporation of a heterologous attachment protein may result in the generation of NDV with altered tropism and/or pathogenicity. Methodology/Principal Findings In the present study we generated recombinant NDVs expressing either full length, membrane-anchored HA of the H5 subtype (NDV-H5) or a soluble trimeric form thereof (NDV-sH53). A single intramuscular immunization with NDV-sH53 or NDV-H5 fully protected chickens against disease after a lethal challenge with H5N1 and reduced levels of virus shedding in tracheal and cloacal swabs. NDV-sH53 was less protective than NDV-H5 (50% vs 80% protection) when administered via the respiratory tract. The NDV-sH53 was ineffective in mice, regardless of whether administered oculonasally or intramuscularly. In this species, NDV-H5 induced protective immunity against HPAIV H5N1, but only after oculonasal administration, despite the poor H5-specific serum antibody response it elicited. Conclusions/Significance Although NDV expressing membrane anchored H5 in general provided better protection than its counterpart expressing soluble H5, chickens could be fully protected against a lethal challenge with H5N1 by using the latter NDV vector. This study thus provides proof of concept for the use of recombinant vector vaccines

  2. Long-Term Effect of Serial Infections with H13 and H16 Low-Pathogenic Avian Influenza Viruses in Black-Headed Gulls

    PubMed Central

    Verhagen, Josanne H.; van Amerongen, Geert; van de Bildt, Marco; Majoor, Frank; Fouchier, Ron A. M.

    2015-01-01

    ABSTRACT Infections of domestic and wild birds with low-pathogenic avian influenza viruses (LPAIVs) have been associated with protective immunity to subsequent infection. However, the degree and duration of immunity in wild birds from previous LPAIV infection, by the same or a different subtype, are poorly understood. Therefore, we inoculated H13N2 (A/black-headed gull/Netherlands/7/2009) and H16N3 (A/black-headed gull/Netherlands/26/2009) LPAIVs into black-headed gulls (Chroicocephalus ridibundus), their natural host species, and measured the long-term immune response and protection against one or two reinfections over a period of >1 year. This is the typical interval between LPAIV epizootics in wild birds. Reinfection with the same virus resulted in progressively less virus excretion, with complete abrogation of virus excretion after two infections for H13 but not H16. However, reinfection with the other virus affected neither the level nor duration of virus excretion. Virus excretion by immunologically naive birds did not differ in total levels of excreted H13 or H16 virus between first- and second-year birds, but the duration of H13 excretion was shorter for second-year birds. Furthermore, serum antibody levels did not correlate with protection against LPAIV infection. LPAIV-infected gulls showed no clinical signs of disease. These results imply that the epidemiological cycles of H13 and H16 in black-headed gulls are relatively independent from each other and depend mainly on infection of first-year birds. IMPORTANCE Low-pathogenic avian influenza viruses (LPAIVs) circulate mainly in wild water birds but are occasionally transmitted to other species, including humans, where they cause subclinical to fatal disease. To date, the effect of LPAIV-specific immunity on the epidemiology of LPAIV in wild birds is poorly understood. In this study, we investigated the effect of H13 and H16 LPAIV infection in black-headed gulls on susceptibility and virus excretion of

  3. The Neuraminidase Stalk Deletion Serves as Major Virulence Determinant of H5N1 Highly Pathogenic Avian Influenza Viruses in Chicken.

    PubMed

    Stech, Olga; Veits, Jutta; Abdelwhab, El-Sayed M; Wessels, Ute; Mettenleiter, Thomas C; Stech, Jürgen

    2015-01-01

    Highly pathogenic avian influenza viruses (HPAIV) cause devastating losses in gallinaceous poultry world-wide and raised concerns of a novel pandemic. HPAIV develop from low-pathogenic precursors by acquisition of a polybasic HA cleavage site (HACS), the prime virulence determinant. Beside that HACS, other adaptive changes accumulate in those precursors prior to transformation into an HPAIV. Here, we aimed to unravel such virulence determinants in addition to the HA gene. Stepwise reduction of HPAIV genes revealed that the HPAIV HA and NA form a minimum set of virulence determinants, sufficient for a lethal phenotype in chicken. Abolishing the NA stalk deletion considerably reduced lethality and prevented transmission. Conversely, the analogous stalk deletion reconstructed in the NA of an LPAIV reassortant carrying only the HPAIV HA resulted in 100% lethality both after primary and contact infection. Remarkably, the unmodified LPAIV NA with its long stalk, when exclusively introduced into the H5N1 HPAIV, still enabled high virulence and efficient transmission. Therefore, irrespective of an NA stalk deletion, minor virulence determinants in addition to the essential polybasic HACS contribute to high virulence, whereas the NA stalk deletion alone may serve as major virulence determinant. PMID:26306544

  4. Evaluation of a commercial ELISA for H5 low pathogenic avian influenza virus antibody detection in duck sera using Bayesian methods.

    PubMed

    Schmitz, Audrey; Le Bras, Marie-Odile; Guillemoto, Carole; Pierre, Isabelle; Rose, Nicolas; Bougeard, Stéphanie; Jestin, Véronique

    2013-10-01

    Following the emergence of highly pathogenic avian influenza (AI), active surveillance of infections due to the H5 and H7 subtypes in poultry has increased and been made compulsory in Europe since 2002, by means of annual serological surveys using the haemagglutination inhibition (HI) test. Domestic anseriforms, particularly ducks and geese, are more frequently infected by H5 low pathogenic AI virus, often subclinically, and represent a threat for other terrestrial poultry. 1783 sera, mainly from ducks, have been used to evaluate and compare a commercial ELISA kit detecting H5 antibodies with the currently recommended HI test. Different approaches to calculating specificity and sensitivity have been used, including the original Bayesian method. Results were similar when data were analyzed at the individual and batch levels, and when using different methods of calculation. However, results showed that H5 ELISA had both a higher sensitivity and a lower specificity than the HI test. Given that sensitivity is the most important factor for a screening test, H5 ELISA could therefore be recommended for AI surveillance, followed in cases of positivity by molecular tests aimed at detecting the virus gene. PMID:23727545

  5. Experimental infection with low and high pathogenicity H7N3 Chilean avian influenza viruses in Chiloe wigeon (Anas sibilatrix) and cinnamon teal (Anas cyanoptera).

    PubMed

    Sá e Silva, Mariana; Mathieu-Benson, Christian; Kwon, Yong-Kuk; Pantin-Jackwood, Mary; Swayne, David E

    2011-09-01

    Two different wild duck species common in Chile and neighboring countries, Chiloe wigeon (Anas sibilatrix) and cinnamon teal (Anas cyanoptera), were intranasally inoculated with 10(6) mean embryo infective dose (EID50) of the H7N3 low pathogenicity (LP) avian influenza virus (AIV) (A/chicken/Chile/176822/02) or high pathogenicity (HP) AIV (A/chicken/Chile/ 184240-1/02), in order to study the infectivity and pathobiology of these viruses. None of the virus-inoculated ducks had clinical signs or died, but most seroconverted by 14 days postinoculation (DPI), indicating a productive virus infection. Both LPAIV and HPAIV were isolated from oral swabs from two of six Chiloe wigeons and from oral and/or cloacal swabs from all five of the cinnamon teal at 2 DPI. Both LPAIV and HPAIV were efficiently transmitted to cinnamon teal contacts but not to Chiloe wigeon contacts. This study demonstrates that the cinnamon teal and Chiloe wigeons were susceptible to infection with both Chilean H7N3 LPAIV and HPAIV, but only the cinnamon teal showed contact transmission of the virus between birds, suggesting that the cinnamon teal has the potential to be a reservoir for these viruses, especially the LPAIV, as was demonstrated in 2001 with isolation of a genetically related H7N3 LPAIV strain in a cinnamon teal in Bolivia. However, the definitive source of the H7N3 Chilean LPAIV still remains unknown. PMID:22017047

  6. The Neuraminidase Stalk Deletion Serves as Major Virulence Determinant of H5N1 Highly Pathogenic Avian Influenza Viruses in Chicken

    PubMed Central

    Stech, Olga; Veits, Jutta; Abdelwhab, El-Sayed M.; Wessels, Ute; Mettenleiter, Thomas C.; Stech, Jürgen

    2015-01-01

    Highly pathogenic avian influenza viruses (HPAIV) cause devastating losses in gallinaceous poultry world-wide and raised concerns of a novel pandemic. HPAIV develop from low-pathogenic precursors by acquisition of a polybasic HA cleavage site (HACS), the prime virulence determinant. Beside that HACS, other adaptive changes accumulate in those precursors prior to transformation into an HPAIV. Here, we aimed to unravel such virulence determinants in addition to the HA gene. Stepwise reduction of HPAIV genes revealed that the HPAIV HA and NA form a minimum set of virulence determinants, sufficient for a lethal phenotype in chicken. Abolishing the NA stalk deletion considerably reduced lethality and prevented transmission. Conversely, the analogous stalk deletion reconstructed in the NA of an LPAIV reassortant carrying only the HPAIV HA resulted in 100% lethality both after primary and contact infection. Remarkably, the unmodified LPAIV NA with its long stalk, when exclusively introduced into the H5N1 HPAIV, still enabled high virulence and efficient transmission. Therefore, irrespective of an NA stalk deletion, minor virulence determinants in addition to the essential polybasic HACS contribute to high virulence, whereas the NA stalk deletion alone may serve as major virulence determinant. PMID:26306544

  7. Experimental selection of virus derivatives with variations in virulence from a single low-pathogenicity H6N1 avian influenza virus field isolate.

    PubMed

    Wang, Ching-Wen; Wang, Ching-Ho

    2003-01-01

    A mixture of viruses with variations in virulence is likely present within a low-pathogenicity avian influenza virus (LPAIV) population. An H6N1 AIV was isolated from a field case showing 3.8% weekly mortality and a 33% egg production drop in Taiwan. The pathologic lesions included proventricular hemorrhage and urate deposition in the kidneys and on visceral organs. From the field isolate, a done (2838N) that caused no lesions or death was obtained using limit dilution in chicken embryos and a done (2838V) that caused renal lesions and death was obtained using contact infection in chicks. Both clones were inoculated intranasally in 4-week-old specific pathogen free (SPF) chickens to test their virulence. Renal urate deposition was found in chickens inoculated with 2838V but not in chickens inoculated with 2838N. In situ hybridization, polymerase chain reaction, and virus isolation were used to confirm the spread of 2838V from the respiratory tract to the renal tissue. We found that contact infection in chickens is a good method to obtain a more virulent done from a heterogeneous virus population. PMID:14708990

  8. Alveolar Type II Epithelial Cells Contribute to the Anti-Influenza A Virus Response in the Lung by Integrating Pathogen- and Microenvironment-Derived Signals

    PubMed Central

    Jeron, Andreas; Gereke, Marcus; Geffers, Robert; Kröger, Andrea; Gunzer, Matthias; Bruder, Dunja

    2016-01-01

    ABSTRACT Influenza A virus (IAV) periodically causes substantial morbidity and mortality in the human population. In the lower lung, the primary targets for IAV replication are type II alveolar epithelial cells (AECII), which are increasingly recognized for their immunological potential. So far, little is known about their reaction to IAV and their contribution to respiratory antiviral immunity in vivo. Therefore, we characterized the AECII response during early IAV infection by analyzing transcriptional regulation in cells sorted from the lungs of infected mice. We detected rapid and extensive regulation of gene expression in AECII following in vivo IAV infection. The comparison to transcriptional regulation in lung tissue revealed a strong contribution of AECII to the respiratory response. IAV infection triggered the expression of a plethora of antiviral factors and immune mediators in AECII with a high prevalence for interferon-stimulated genes. Functional pathway analyses revealed high activity in pathogen recognition, immune cell recruitment, and antigen presentation. Ultimately, our analyses of transcriptional regulation in AECII and lung tissue as well as interferon I/III levels and cell recruitment indicated AECII to integrate signals provided by direct pathogen recognition and surrounding cells. Ex vivo analysis of AECII proved a powerful tool to increase our understanding of their role in respiratory immune responses, and our results clearly show that AECII need to be considered a part of the surveillance and effector system of the lower respiratory tract. PMID:27143386

  9. 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. PMID:25231137

  10. Intranasal Immunization of Baculovirus Displayed Hemagglutinin Confers Complete Protection against Mouse Adapted Highly Pathogenic H7N7 Reassortant Influenza Virus

    PubMed Central

    Rajesh Kumar, Subaschandrabose; Syed Khader, Syed Musthaq; Kiener, Tanja K.; Szyporta, Milene; Kwang, Jimmy

    2013-01-01

    Background Avian influenza A H7N7 virus poses a pandemic threat to human health because of its ability for direct transmission from domestic poultry to humans and from human to human. The wide zoonotic potential of H7N7 combined with an antiviral immunity inhibition similar to pandemic 1918 H1N1 and 2009 H1N1 influenza viruses is disconcerting and increases the risk of a putative H7N7 pandemic in the future, underlining the urgent need for vaccine development against this virus. Methodology/Principal Findings In this study, we developed a recombinant vaccine by expressing the H7N7-HA protein on the surface of baculovirus (Bac-HA). The protective efficacy of the live Bac-HA vaccine construct was evaluated in a mouse model by challenging mice immunized intranasally (i.n.) or subcutaneously (s.c.) with high pathogenic mouse adapted H7N7 reassorted strain. Although s.c. injection of live Bac-HA induced higher specific IgG than i.n. immunization, the later resulted in an elevated neutralization titer. Interestingly, 100% protection from the lethal viral challenge was only observed for the mice immunized intranasally with live Bac-HA, whereas no protection was achieved in any other s.c. or i.n. immunized mice groups. In addition, we also observed higher mucosal IgA as well as increased IFN-γ and IL-4 responses in the splenocytes of the surviving mice coupled with a reduced viral titer and diminished histopathological signs in the lungs. Conclusion Our results indicated that protection from high pathogenic H7N7 (NL/219/03) virus requires both mucosal and systemic immune responses in mice. The balance between Th1 and Th2 cytokines is also required for the protection against the H7N7 pathogen. Intranasal administration of live Bac-HA induced all these immune responses and protected the mice from lethal viral challenge. Therefore, live Bac-HA is an effective vaccine candidate against H7N7 viral infections. PMID:23762234

  11. Pathogenesis and Transmission of Novel Highly Pathogenic Avian Influenza H5N2 and H5N8 Viruses in Ferrets and Mice

    PubMed Central

    Pulit-Penaloza, Joanna A.; Sun, Xiangjie; Creager, Hannah M.; Zeng, Hui; Belser, Jessica A.; Maines, Taronna R.

    2015-01-01

    ABSTRACT A novel highly pathogenic avian influenza (HPAI) H5N8 virus, first detected in January 2014 in poultry and wild birds in South Korea, has spread throughout Asia and Europe and caused outbreaks in Canada and the United States by the end of the year. The spread of H5N8 and the novel reassortant viruses, H5N2 and H5N1 (H5Nx), in domestic poultry across multiple states in the United States pose a potential public health risk. To evaluate the potential of cross-species infection, we determined the pathogenicity and transmissibility of two Asian-origin H5Nx viruses in mammalian animal models. The newly isolated H5N2 and H5N8 viruses were able to cause severe disease in mice only at high doses. Both viruses replicated efficiently in the upper and lower respiratory tracts of ferrets; however, the clinical symptoms were generally mild, and there was no evidence of systemic dissemination of virus to multiple organs. Moreover, these influenza H5Nx viruses lacked the ability to transmit between ferrets in a direct contact setting. We further assessed viral replication kinetics of the novel H5Nx viruses in a human bronchial epithelium cell line, Calu-3. Both H5Nx viruses replicated to a level comparable to a human seasonal H1N1 virus, but significantly lower than a virulent Asian-lineage H5N1 HPAI virus. Although the recently isolated H5N2 and H5N8 viruses displayed moderate pathogenicity in mammalian models, their ability to rapidly spread among avian species, reassort, and generate novel strains underscores the need for continued risk assessment in mammals. IMPORTANCE In 2015, highly pathogenic avian influenza (HPAI) H5 viruses have caused outbreaks in domestic poultry in multiple U.S. states. The economic losses incurred with H5N8 and H5N2 subtype virus infection have raised serious concerns for the poultry industry and the general public due to the potential risk of human infection. This recent outbreak underscores the need to better understand the pathogenesis and

  12. 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

    2016-01-15

    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. PMID:26711036

  13. Serological Evidence for Non-Lethal Exposures of Mongolian Wild Birds to Highly Pathogenic Avian Influenza H5N1 Virus

    PubMed Central

    Gilbert, Martin; Koel, Björn F.; Bestebroer, Theo M.; Lewis, Nicola S.; Smith, Derek J.; Fouchier, Ron A. M.

    2014-01-01

    Surveillance for highly pathogenic avian influenza viruses (HPAIV) in wild birds is logistically demanding due to the very low rates of virus detection. Serological approaches may be more cost effective as they require smaller sample sizes to identify exposed populations. We hypothesized that antigenic differences between classical Eurasian H5 subtype viruses (which have low pathogenicity in chickens) and H5N1 viruses of the Goose/Guangdong/96 H5 lineage (which are HPAIV) may be used to differentiate populations where HPAIVs have been circulating, from those where they have not. To test this we performed hemagglutination inhibition assays to compare the reactivity of serum samples from wild birds in Mongolia (where HPAIV has been circulating, n = 1,832) and Europe (where HPAIV has been rare or absent, n = 497) to a panel of reference viruses including classical Eurasian H5 (of low pathogenicity), and five HPAIV H5N1 antigens of the Asian lineage A/Goose/Guangdong/1/96. Antibody titres were detected against at least one of the test antigens for 182 Mongolian serum samples (total seroprevalence of 0.10, n = 1,832, 95% adjusted Wald confidence limits of 0.09–0.11) and 25 of the European sera tested (total seroprevalence of 0.05, n = 497, 95% adjusted Wald confidence limits of 0.03–0.07). A bias in antibody titres to HPAIV antigens was found in the Mongolian sample set (22/182) that was absent in the European sera (0/25). Although the interpretation of serological data from wild birds is complicated by the possibility of exposure to multiple strains, and variability in the timing of exposure, these findings suggest that a proportion of the Mongolian population had survived exposure to HPAIV, and that serological assays may enhance the targeting of traditional HPAIV surveillance toward populations where isolation of HPAIV is more likely. PMID:25502318

  14. Rapid emergence of a virulent PB2 E627K variant during adaptation of highly pathogenic avian influenza H7N7 virus to mice

    PubMed Central

    2013-01-01

    Background Highly pathogenic avian influenza (HPAI) viruses pose a potential human health threat as they can be transmitted directly from infected poultry to humans. During a large outbreak of HPAI H7N7 virus among poultry in The Netherlands in 2003, bird to human transmission was confirmed in 89 cases, of which one had a fatal outcome. Methods To identify genetic determinants of virulence in a mammalian host, we passaged an avian H7N7/03 outbreak isolate in mouse lungs and evaluated the phenotype of the mouse-adapted variant in animal models and in vitro. Results Three passages in mouse lungs were sufficient to select a variant that was highly virulent in mice. The virus had a MLD50 that was >4.3 logs lower than that of its non-lethal parental virus. Sequence analysis revealed a single mutation at position 627 in PB2, where the glutamic acid was changed to a lysine (E627K). The mouse-adapted virus has this mutation in common with the fatal human case isolate. The virus remained highly pathogenic for chickens after its passage in mice. In ferrets, the mouse-adapted virus induced more severe disease, replicated to higher titers in the lower respiratory tract and spread more efficiently to systemic organs compared with the parental virus. In vitro, the PB2 E627K mutation had a promoting effect on virus propagation in mammalian, but not in avian cells. Conclusions Our results show that the E627K mutation in PB2 alone can be sufficient to convert an HPAI H7N7 virus of low virulence to a variant causing severe disease in mice and ferrets. The rapid emergence of the PB2 E627K mutant during mouse adaptation and its pathogenicity in ferrets emphasize the potential risk of HPAI H7N7 viruses for human health. PMID:24007444

  15. Neuroinvasion of the Highly Pathogenic Influenza Virus H7N1 Is Caused by Disruption of the Blood Brain Barrier in an Avian Model

    PubMed Central

    Chaves, Aida J.; Vergara-Alert, Júlia; Busquets, Núria; Valle, Rosa; Rivas, Raquel; Ramis, Antonio; Darji, Ayub; Majó, Natàlia

    2014-01-01

    Influenza A virus (IAV) causes central nervous system (CNS) lesions in avian and mammalian species, including humans. However, the mechanism used by IAV to invade the brain has not been determined. In the current work, we used chickens infected with a highly pathogenic avian influenza (HPAI) virus as a model to elucidate the mechanism of entry of IAV into the brain. The permeability of the BBB was evaluated in fifteen-day-old H7N1-infected and non-infected chickens using three different methods: (i) detecting Evans blue (EB) extravasation into the brain, (ii) determining the leakage of the serum protein immunoglobulin Y (IgY) into the brain and (iii) assessing the stability of the tight-junction (TJ) proteins zonula occludens-1 and claudin-1 in the chicken brain at 6, 12, 18, 24, 36 and 48 hours post-inoculation (hpi). The onset of the induced viremia was evaluated by quantitative real time RT-PCR (RT-qPCR) at the same time points. Viral RNA was detected from 18 hpi onward in blood samples, whereas IAV antigen was detected at 24 hpi in brain tissue samples. EB and IgY extravasation and loss of integrity of the TJs associated with the presence of viral antigen was first observed at 36 and 48 hpi in the telencephalic pallium and cerebellum. Our data suggest that the mechanism of entry of the H7N1 HPAI into the brain includes infection of the endothelial cells at early stages (24 hpi) with subsequent disruption of the TJs of the BBB and leakage of virus and serum proteins into the adjacent neuroparenchyma. PMID:25506836

  16. Live vaccination with an H5-hemagglutinin-expressing infectious laryngotracheitis virus recombinant protects chickens against different highly pathogenic avian influenza viruses of the H5 subtype.

    PubMed

    Pavlova, Sophia P; Veits, Jutta; Mettenleiter, Thomas C; Fuchs, Walter

    2009-08-13

    Recently, we described an infectious laryngotracheitis virus (ILTV, gallid herpesvirus 1) recombinant, which had been attenuated by deletion of the viral dUTPase gene UL50, and abundantly expressed the hemagglutinin (HA) gene of a H5N1 type highly pathogenic avian influenza virus (HPAIV) of Vietnamese origin. In the present study, efficacy of this vectored vaccine (ILTV-DeltaUL50IH5V) against different H5 HPAIV was evaluated in 6-week-old chickens. After a single ocular immunization all animals developed HA-specific antibodies, and were protected against lethal infection not only with the homologous HPAIV isolate A/duck/Vietnam/TG24-01/2005 (H5N1, clade 1, hemagglutinin amino acid sequence identity 100%), but also with heterologous HPAIV A/swan/Germany/R65/2006 (H5N1, clade 2.2, identity 96.1%) or HPAIV A/chicken/Italy/8/98 (H5N2, identity 93.8%). No symptoms of disease were observed after challenge with the H5N1 viruses, and only 20% of H5N2 challenged animals developed minimal clinical signs. Real-time RT-PCR analyses of oropharyngeal swabs revealed limited challenge virus replication, but the almost complete absence of HPAIV RNA from cloacal swabs indicated that no generalized infections occurred. Thus, unlike several previous vectors, ILTV-DeltaUL50IH5V was able to protect chickens against different HPAIV isolates of the H5 subtype. Vaccination with HA-expressing ILTV also allowed differentiation of immunized from AIV-infected animals by serological tests for antibodies against influenza virus nucleoprotein. PMID:19573638

  17. Susceptibility to and transmission of H5N1 and H7N1 highly pathogenic avian influenza viruses in bank voles (Myodes glareolus).

    PubMed

    Romero Tejeda, Aurora; Aiello, Roberta; Salomoni, Angela; Berton, Valeria; Vascellari, Marta; Cattoli, Giovanni

    2015-01-01

    The study of influenza type A (IA) infections in wild mammals populations is a critical gap in our knowledge of how IA viruses evolve in novel hosts that could be in close contact with avian reservoir species and other wild animals. The aim of this study was to evaluate the susceptibility to infection, the nasal shedding and the transmissibility of the H7N1 and H5N1 highly pathogenic avian influenza (HPAI) viruses in the bank vole (Myodes glareolus), a wild rodent common throughout Europe and Asia. Two out of 24 H5N1-infected voles displayed evident respiratory distress, while H7N1-infected voles remained asymptomatic. Viable virus was isolated from nasal washes collected from animals infected with both HPAI viruses, and extra-pulmonary infection was confirmed in both experimental groups. Histopathological lesions were evident in the respiratory tract of infected animals, although immunohistochemistry positivity was only detected in lungs and trachea of two H7N1-infected voles. Both HPAI viruses were transmitted by direct contact, and seroconversion was confirmed in 50% and 12.5% of the asymptomatic sentinels in the H7N1 and H5N1 groups, respectively. Interestingly, viable virus was isolated from lungs and nasal washes collected from contact sentinels of both groups. The present study demonstrated that two non-rodent adapted HPAI viruses caused asymptomatic infection in bank voles, which shed high amounts of the viruses and were able to infect contact voles. Further investigations are needed to determine whether bank voles could be involved as silent hosts in the transmission of HPAI viruses to other mammals and domestic poultry. PMID:25963535

  18. Highly Pathogenic Avian Influenza Virus Subtype H5N1 in Africa: A Comprehensive Phylogenetic Analysis and Molecular Characterization of Isolates

    PubMed Central

    Cattoli, Giovanni; Monne, Isabella; Fusaro, Alice; Joannis, Tony M.; Lombin, Lami H.; Aly, Mona M.; Arafa, Abdel S.; Sturm-Ramirez, Katharine M.; Couacy-Hymann, Emmanuel; Awuni, Joseph A.; Batawui, Komla B.; Awoume, Kodzo A.; Aplogan, Gilbert L.; Sow, Adama; Ngangnou, Andrè C.; El Nasri Hamza, Iman M.; Gamatié, Djibo; Dauphin, Gwenaelle; Domenech, Joseph M.; Capua, Ilaria

    2009-01-01

    Highly pathogenic avian influenza virus A/H5N1 was first officially reported in Africa in early 2006. Since the first outbreak in Nigeria, this virus spread rapidly to other African countries. From its emergence to early 2008, 11 African countries experienced A/H5N1 outbreaks in poultry and human cases were also reported in three of these countries. At present, little is known of the epidemiology and molecular evolution of A/H5N1 viruses in Africa. We have generated 494 full gene sequences from 67 African isolates and applied molecular analysis tools to a total of 1,152 A/H5N1 sequences obtained from viruses isolated in Africa, Europe and the Middle East between 2006 and early 2008. Detailed phylogenetic analyses of the 8 gene viral segments confirmed that 3 distinct sublineages were introduced, which have persisted and spread across the continent over this 2-year period. Additionally, our molecular epidemiological studies highlighted the association between genetic clustering and area of origin in a majority of cases. Molecular signatures unique to strains isolated in selected areas also gave us a clearer picture of the spread of A/H5N1 viruses across the continent. Mutations described as typical of human influenza viruses in the genes coding for internal proteins or associated with host adaptation and increased resistance to antiviral drugs have also been detected in the genes coding for transmembrane proteins. These findings raise concern for the possible human health risk presented by viruses with these genetic properties and highlight the need for increased efforts to monitor the evolution of A/H5N1 viruses across the African continent. They further stress how imperative it is to implement sustainable control strategies to improve animal and public health at a global level. PMID:19290041

  19. Cytomegalovirus as nosocomial infection.

    PubMed

    Román González, J; Colón, M; Ramírez-Ronda, C H

    1991-08-01

    Nosocomial infections with cytomegalovirus are an area of great concern and controversy within the medical community. With the advent of organ transplantation there have been an increased number of susceptible individuals. In the past most cases were confined to newborn nurseries and the neonatal intensive care unit. It is of great interest that recent evidence suggests that health care providers are at no greater risk of acquiring CMV infection inside the hospital setting when compared to a representative control group within the same community. This paper will review some of the literature that deals with the nosocomial transmission of CMV. We will try to emphasize transmission, diagnosis, prevention, and treatment of CMV infection. PMID:1667848

  20. Immunization of Chickens with Newcastle Disease Virus Expressing H5 Hemagglutinin Protects against Highly Pathogenic H5N1 Avian Influenza Viruses

    PubMed Central

    Nayak, Baibaswata; Rout, Subrat N.; Kumar, Sachin; Khalil, Mohammed S.; Fouda, Moustafa M.; Ahmed, Luay E.; Earhart, Kenneth C.; Perez, Daniel R.; Collins, Peter L.; Samal, Siba K.

    2009-01-01

    Background Highly-pathogenic avian influenza virus (HPAIV) and Newcastle disease virus (NDV) are the two most important poultry viruses in the world. Natural low-virulence NDV strains have been used as vaccines over the past 70 years with proven track records. We have previously developed a reverse genetics system to produce low-virulent NDV vaccine strain LaSota from cloned cDNA. This system allows us to use NDV as a vaccine vector for other avian pathogens. Methodology/Principal Finding Here, we constructed two recombinant NDVs (rNDVs) each of which expresses the hemagglutinin (HA) gene of HPAIV H5N1strain A/Vietnam/1203/2004 from an added gene. In one, rNDV (rNDV-HA), the open reading frame (ORF) of HA gene was expressed without modification. In the second, rNDV (rNDV-HAF), the ORF was modified so that the transmembrane and cytoplasmic domains of the encoded HA gene were replaced with those of the NDV F protein. The insertion of either version of the HA ORF did not increase the virulence of the rNDV vector. The HA protein was found to be incorporated into the envelopes of both rNDV-HA and rNDV-HAF. However, there was an enhanced incorporation of the HA protein in rNDV-HAF. Chickens immunized with a single dose of either rNDV-HA or rNDV-HAF induced a high titer of HPAIV H5-specific antibodies and were completely protected against challenge with NDV as well as lethal challenges of both homologous and heterologous HPAIV H5N1. Conclusion and Significance Our results suggest that these chimeric viruses have potential as safe and effective bivalent vaccines against NDV and. HPAIV. These vaccines will be convenient and affordable, which will be highly beneficial to the poultry industry. Furthermore, immunization with these vaccines will permit serological differentiation of vaccinated and avian influenza field virus infected animals. PMID:19654873

  1. Quantitative Estimation of the Number of Contaminated Hatching Eggs Released from an Infected, Undetected Turkey Breeder Hen Flock During a Highly Pathogenic Avian Influenza Outbreak.

    PubMed

    Malladi, Sasidhar; Weaver, J Todd; Alexander, Catherine Y; Middleton, Jamie L; Goldsmith, Timothy J; Snider, Timothy; Tilley, Becky J; Gonder, Eric; Hermes, David R; Halvorson, David A

    2015-09-01

    The regulatory response to an outbreak of highly pathogenic avian influenza (HPAI) in the United States may involve quarantine and stop movement orders that have the potential to disrupt continuity of operations in the U.S. turkey industry--particularly in the event that an uninfected breeder flock is located within an HPAI Control Area. A group of government-academic-industry leaders developed an approach to minimize the unintended consequences associated with outbreak response, which incorporates HPAI control measures to be implemented prior to moving hatching eggs off of the farm. Quantitative simulation models were used to evaluate the movement of potentially contaminated hatching eggs from a breeder henhouse located in an HPAI Control Area, given that active surveillance testing, elevated biosecurity, and a 2-day on-farm holding period were employed. The risk analysis included scenarios of HPAI viruses differing in characteristics as well as scenarios in which infection resulted from artificial insemination. The mean model-predicted number of internally contaminated hatching eggs released per movement from an HPAI-infected turkey breeder henhouse ranged from 0 to 0.008 under the four scenarios evaluated. The results indicate a 95% chance of no internally contaminated eggs being present per movement from an infected house before detection. Sensitivity analysis indicates that these results are robust to variation in key transmission model parameters within the range of their estimates from available literature. Infectious birds at the time of egg collection are a potential pathway of external contamination for eggs stored and then moved off of the farm; the predicted number of such infectious birds was estimated to be low. To date, there has been no evidence of vertical transmission of HPAI virus or low pathogenic avian influenza virus to day-old poults from hatching eggs originating from infected breeders. The application of risk analysis methods was beneficial

  2. Major histocompatibility complex and host background genes in chickens influence resistance to high pathogenicity avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The chicken’s major histocompatibility complex (MHC) haplotype has a profound influence on the resistance or susceptibility to certain pathogens such as B21 MHC haplotype confers resistance to Marek’s disease (MD). However, non-MHC genes are also important in disease resistance. For example, both li...

  3. Dual RNA-seq of Nontypeable Haemophilus influenzae and Host Cell Transcriptomes Reveals Novel Insights into Host-Pathogen Cross Talk

    PubMed Central

    Baddal, Buket; Muzzi, Alessandro; Censini, Stefano; Calogero, Raffaele A.; Torricelli, Giulia; Guidotti, Silvia; Taddei, Anna R.; Covacci, Antonello; Pizza, Mariagrazia; Rappuoli, Rino; Pezzicoli, Alfredo

    2015-01-01

    ABSTRACT The ability to adhere and adapt to the human respiratory tract mucosa plays a pivotal role in the pathogenic lifestyle of nontypeable Haemophilus influenzae (NTHi). However, the temporal events associated with a successful colonization have not been fully characterized. In this study, by reconstituting the ciliated human bronchial epithelium in vitro, we monitored the global transcriptional changes in NTHi and infected mucosal epithelium simultaneously for up to 72 h by dual RNA sequencing. The initial stage of colonization was characterized by the binding of NTHi to ciliated cells. Temporal profiling of host mRNA signatures revealed significant dysregulation of the target cell cytoskeleton elicited by bacterial infection, with a profound effect on the intermediate filament network and junctional complexes. In response to environmental stimuli of the host epithelium, NTHi downregulated its central metabolism and increased the expression of transporters, indicating a change in the metabolic regime due to the availability of host substrates. Concurrently, the oxidative environment generated by infected cells instigated bacterial expression of stress-induced defense mechanisms, including the transport of exogenous glutathione and activation of the toxin-antitoxin system. The results of this analysis were validated by those of confocal microscopy, Western blotting, Bio-plex, and real-time quantitative reverse transcription-PCR (qRT-PCR). Notably, as part of our screening for novel signatures of infection, we identified a global profile of noncoding transcripts that are candidate small RNAs (sRNAs) regulated during human host infection in Haemophilus species. Our data, by providing a robust and comprehensive representation of the cross talk between the host and invading pathogen, provides important insights into NTHi pathogenesis and the development of efficacious preventive strategies. PMID:26578681

  4. Epidemic outbreaks, diagnostics, and control measures of the H5N1 highly pathogenic avian influenza in the Kingdom of Saudi Arabia, 2007-08.

    PubMed

    Lu, Huaguang; Ismail, Mahmoud Moussa; Khan, Owais Ahmed; Al Hammad, Yousef; Abdel Rhman, Salah Shaban; Al-Blowi, Mohamed Hamad

    2010-03-01

    The first outbreak of H5N1 highly pathogenic avian influenza (HPAI) in the Kingdom of Saudi Arabia (KSA) occurred in two "backyard" flocks of Houbara bustards and falcons in February 2007. Subsequent outbreaks were seen through the end of 2007 in "backyard" birds including native chickens, ostriches, turkeys, ducks, and peacocks. From November 2007 through January 2008, H5N1 HPAI outbreaks occurred in 19 commercial poultry premises, including two broiler breeder farms, one layer breeder farm, one ostrich farm, and 15 commercial layer farms, with approximately 4.75 million birds affected. Laboratory diagnosis of all H5N1-positive cases was conducted at the Central Veterinary Diagnostic Laboratory (CVDL) in Riyadh, Saudi Arabia. A combination of diagnostic tests was used to confirm the laboratory diagnosis. A rapid antigen-capture test and real-time reverse transcriptase-PCR (rtRT-PCR) assay on clinical and field specimens were conducted initially. Meanwhile, virus isolation in specific-pathogen-free embryonating chicken eggs was performed and was followed by hemagglutinin (HA) and hemagglutination inhibition tests, then rapid antigen-capture and rtRT-PCR tests on HA-positive allantoic fluid samples. In most HPAI cases, a complete laboratory diagnosis was made within 24-48 hr at the CVDL. Saudi Arabian government officials made immediate decisions to depopulate all H5N1-affected and nonaffected flocks within a 5-km radius area and applied quarantine zones to prevent the virus from spreading to other areas. Other control measures, such as closure of live bird markets and intensive surveillance tests on all poultry species within quarantine zones, were in place during the outbreaks. As a result, the HPAI outbreaks were quickly controlled, and no positive cases were detected after January 29, 2008. The KSA was declared free of HPAI on April 30, 2008, by the World Animal Health Organization. PMID:20521658

  5. Novel Highly Pathogenic Avian A(H5N2) and A(H5N8) Influenza Viruses of Clade 2.3.4.4 from North America Have Limited Capacity for Replication and Transmission in Mammals

    PubMed Central

    Kaplan, Bryan S.; Russier, Marion; Jeevan, Trushar; Marathe, Bindumadhav; Govorkova, Elena A.; Russell, Charles J.; Kim-Torchetti, Mia; Choi, Young Ki; Brown, Ian; Saito, Takehiko; Stallknecht, David E.; Krauss, Scott

    2016-01-01

    ABSTRACT Highly pathogenic influenza A(H5N8) viruses from clade 2.3.4.4 were introduced to North America by migratory birds in the fall of 2014. Reassortment of A(H5N8) viruses with avian viruses of North American lineage resulted in the generation of novel A(H5N2) viruses with novel genotypes. Through sequencing of recent avian influenza viruses, we identified PB1 and NP gene segments very similar to those in the viruses isolated from North American waterfowl prior to the introduction of A(H5N8) to North America, highlighting these bird species in the origin of reassortant A(H5N2) viruses. While they were highly virulent and transmissible in poultry, we found A(H5N2) viruses to be low pathogenic in mice and ferrets, and replication was limited in both hosts compared with those of recent highly pathogenic avian influenza (HPAI) H5N1 viruses. Molecular characterization of the hemagglutinin protein from A(H5N2) viruses showed that the receptor binding preference, cleavage, and pH of activation were highly adapted for replication in avian species and similar to those of other 2.3.4.4 viruses. In addition, North American and Eurasian clade 2.3.4.4 H5NX viruses replicated to significantly lower titers in differentiated normal human bronchial epithelial cells than did seasonal human A(H1N1) and highly pathogenic A(H5N1) viruses isolated from a human case. Thus, despite their having a high impact on poultry, our findings suggest that the recently emerging North American A(H5N2) viruses are not expected to pose a substantial threat to humans and other mammals without further reassortment and/or adaptation and that reassortment with North American viruses has not had a major impact on viral phenotype. IMPORTANCE Highly pathogenic H5 influenza viruses have been introduced into North America from Asia, causing extensive morbidity and mortality in domestic poultry. The introduced viruses have reassorted with North American avian influenza viruses, generating viral genotypes

  6. Novel Highly Pathogenic Avian A(H5N2) and A(H5N8) Influenza Viruses of Clade 2.3.4.4 from North America Have Limited Capacity for Replication and Transmission in Mammals.

    PubMed

    Kaplan, Bryan S; Russier, Marion; Jeevan, Trushar; Marathe, Bindumadhav; Govorkova, Elena A; Russell, Charles J; Kim-Torchetti, Mia; Choi, Young Ki; Brown, Ian; Saito, Takehiko; Stallknecht, David E; Krauss, Scott; Webby, Richard J

    2016-01-01

    Highly pathogenic influenza A(H5N8) viruses from clade 2.3.4.4 were introduced to North America by migratory birds in the fall of 2014. Reassortment of A(H5N8) viruses with avian viruses of North American lineage resulted in the generation of novel A(H5N2) viruses with novel genotypes. Through sequencing of recent avian influenza viruses, we identified PB1 and NP gene segments very similar to those in the viruses isolated from North American waterfowl prior to the introduction of A(H5N8) to North America, highlighting these bird species in the origin of reassortant A(H5N2) viruses. While they were highly virulent and transmissible in poultry, we found A(H5N2) viruses to be low pathogenic in mice and ferrets, and replication was limited in both hosts compared with those of recent highly pathogenic avian influenza (HPAI) H5N1 viruses. Molecular characterization of the hemagglutinin protein from A(H5N2) viruses showed that the receptor binding preference, cleavage, and pH of activation were highly adapted for replication in avian species and similar to those of other 2.3.4.4 viruses. In addition, North American and Eurasian clade 2.3.4.4 H5NX viruses replicated to significantly lower titers in differentiated normal human bronchial epithelial cells than did seasonal human A(H1N1) and highly pathogenic A(H5N1) viruses isolated from a human case. Thus, despite their having a high impact on poultry, our findings suggest that the recently emerging North American A(H5N2) viruses are not expected to pose a substantial threat to humans and other mammals without further reassortment and/or adaptation and that reassortment with North American viruses has not had a major impact on viral phenotype. IMPORTANCE Highly pathogenic H5 influenza viruses have been introduced into North America from Asia, causing extensive morbidity and mortality in domestic poultry. The introduced viruses have reassorted with North American avian influenza viruses, generating viral genotypes not seen on

  7. Highly Pathogenic H5N1 and Novel H7N9 Influenza A Viruses Induce More Profound Proteomic Host Responses than Seasonal and Pandemic H1N1 Strains.

    PubMed

    Simon, Philippe François; McCorrister, Stuart; Hu, Pingzhao; Chong, Patrick; Silaghi, Alex; Westmacott, Garrett; Coombs, Kevin M; Kobasa, Darwyn

    2015-11-01

    Influenza A viruses (IAV) are important human and animal pathogens with potential for causing pandemics. IAVs exhibit a wide spectrum of clinical illness in humans, from relatively mild infections by seasonal strains to acute respiratory distress syndrome during infections with some highly pathogenic avian influenza (HPAI) viruses. In the present study, we infected A549 human cells with seasonal H1N1 (sH1N1), 2009 pandemic H1N1 (pdmH1N1), or novel H7N9 and HPAI H5N1 strains. We used multiplexed isobaric tags for relative and absolute quantification to measure proteomic host responses to these different strains at 1, 3, and 6 h post-infection. Our analyses revealed that both H7N9 and H5N1 strains induced more profound changes to the A549 global proteome compared to those with low-pathogenicity H1N1 virus infection, which correlates with the higher pathogenicity these strains exhibit at the organismal level. Bioinformatics analysis revealed important modulation of the nuclear factor erythroid 2-related factor 2 (NRF2) oxidative stress response in infection. Cellular fractionation and Western blotting suggested that the phosphorylated form of NRF2 is not imported to the nucleus in H5N1 and H7N9 virus infections. Fibronectin was also strongly inhibited in infection with H5N1 and H7N9 strains. This is the first known comparative proteomic study of the host response to H7N9, H5N1, and H1N1 viruses and the first time NRF2 is shown to be implicated in infection with highly pathogenic strains of influenza. PMID:26381135

  8. Investigation into the Airborne Dissemination of H5N2 Highly Pathogenic Avian Influenza Virus During the 2015 Spring Outbreaks in the Midwestern United States.

    PubMed

    Torremorell, Montserrat; Alonso, Carmen; Davies, Peter R; Raynor, Peter C; Patnayak, Devi; Torchetti, Mia; McCluskey, Brian

    2016-09-01

    We investigated the plausibility of aerosol transmission of H5N2 highly pathogenic avian influenza (HPAI) virus during the 2015 spring outbreaks that occurred in the U.S. midwest. Air samples were collected inside and outside of infected turkey and layer facilities. Samples were tested to assess HPAI virus concentration (RNA copies/m(3) of air), virus viability, and virus distribution by particle size. HPAI virus RNA was detected inside and up to 1000 m from infected facilities. HPAI virus was isolated from air samples collected inside, immediately outside, up to 70 m from infected facilities, and in aerosol particles larger than 2.1 μm. Direct exposure to exhausted aerosols proved to be a significant source of environmental contamination. These findings demonstrate HPAI virus aerosolization from infected flocks, and that both the transport of infectious aerosolized particles and the deposition of particles on surfaces around infected premises represent a potential risk for the spread of HPAI. PMID:27610723

  9. Incursion and spread of H5N1 highly pathogenic avian influenza viruses among wild birds in 2010-11 winter in Japan.

    PubMed

    Soda, Kosuke; Ito, Hiroshi; Usui, Tatsufumi; Nagai, Yasuko; Ozaki, Hiroichi; Yamaguchi, Tsuyoshi; Ito, Toshihiro

    2013-01-01

    Many highly pathogenic avian influenza (HPAI) outbreaks occurred in Japan during the 2010-11 winter. H5N1 HPAI viruses were isolated from 63 wild birds including migrating and resident birds, and caused HPAI outbreaks in 24 chicken farms by the end of March. In the present study, all virus strains isolated from wild birds in western Japan together with the viruses in the preceding works were phylogenetically and epidemiologically analyzed. Furthermore, the virus distributions in the raptors that died of H5N1 HPAI virus infection were assessed. The virus isolates in Japan were classified into three groups by phylogenic analysis of their hemagglutinins, supporting the previous report (Sakoda et al., 2012). The viruses in each group were continuously isolated in respective limited areas, indicating that viruses were maintained in local bird populations throughout the outbreak periods. Some viruses were genetically closely related to the Korean isolates around the same periods, suggesting that migratory birds were suspected of contributing to transportation of the viruses across the sea. Viruses were recovered from systemic tissues including digestive organs of the deceased raptors, indicating that they were infected with HPAI viruses by their predatory behavior, eating infected birds or carrion in the environment. PMID:23292107

  10. Phylodynamics of H5N1 Highly Pathogenic Avian Influenza in Europe, 2005-2010: Potential for Molecular Surveillance of New Outbreaks.

    PubMed

    Alkhamis, Mohammad A; Moore, Brian R; Perez, Andres M

    2015-06-01

    Previous Bayesian phylogeographic studies of H5N1 highly pathogenic avian influenza viruses (HPAIVs) explored the origin and spread of the epidemic from China into Russia, indicating that HPAIV circulated in Russia prior to its detection there in 2005. In this study, we extend this research to explore the evolution and spread of HPAIV within Europe during the 2005-2010 epidemic, using all available sequences of the hemagglutinin (HA) and neuraminidase (NA) gene regions that were collected in Europe and Russia during the outbreak. We use discrete-trait phylodynamic models within a Bayesian statistical framework to explore the evolution of HPAIV. Our results indicate that the genetic diversity and effective population size of HPAIV peaked between mid-2005 and early 2006, followed by drastic decline in 2007, which coincides with the end of the epidemic in Europe. Our results also suggest that domestic birds were the most likely source of the spread of the virus from Russia into Europe. Additionally, estimates of viral dispersal routes indicate that Russia, Romania, and Germany were key epicenters of these outbreaks. Our study quantifies the dynamics of a major European HPAIV pandemic and substantiates the ability of phylodynamic models to improve molecular surveillance of novel AIVs. PMID:26110587

  11. Characterization and phylogenetic analysis of a highly pathogenic avian influenza H5N1 virus isolated from diseased ostriches (Struthio camelus) in the Kingdom of Saudi Arabia.

    PubMed

    Ismail, Mahmoud Moussa; El-Sabagh, I M; Al-Ankari, Abdul-Rahman

    2014-06-01

    During 2007, two outbreaks of avian influenza virus (AIV) in backyard and commercial ostrich flocks were first reported in the Kingdom of Saudi Arabia (KSA). The infected ostriches suffered from depression, anorexia, and diarrhea and some exhibited sudden death. A rapid AIV-group antigen detection and real-time reverse-transcription PCR (rtRT-PCR) were initially performed on cloacal and tracheal swabs collected from diseased birds. Pools from positive-tested swabs for each flock were utilized for virus isolation in specific-pathogen-free embryonating chicken eggs. H5N1 AIV was identified in the harvested allantoic fluids by hemagglutination followed by hemagglutination inhibition and rtRT-PCR. The viruses responsible for these two outbreaks were sequenced and characterized as HPAIV H5N1 (A/ostrich/Saudi Arabia/6732-3/2007 and A/ostrich/Saudi Arabia/3489-73VIR08/ 2007) from backyard and commercial flocks, respectively. Phylogenetic analysis of both isolates revealed that the two viruses belong to clade 2.2 sublineage II and cluster with the HPAIV H5N1 isolated from falcons and turkeys during 2007 in KSA. PMID:25055639

  12. Southward autumn migration of waterfowl facilitates cross-continental transmission of the highly pathogenic avian influenza H5N1 virus.

    PubMed

    Xu, Yanjie; Gong, Peng; Wielstra, Ben; Si, Yali

    2016-01-01

    The highly pathogenic avian influenza subtype H5N1 (HPAI H5N1) is a worldwide zoonotic infectious disease, threatening humans, poultry and wild birds. The role of wild birds in the spread of HPAI H5N1 has previously been investigated by comparing disease spread patterns with bird migration routes. However, the different roles that the southward autumn and northward spring migration might play in virus transmission have hardly been explored. Using direction analysis, we analyze HPAI H5N1 transmission directions and angular concentration of currently circulating viral clades, and compare these with waterfowl seasonal migration directions along major waterfowl flyways. Out of 22 HPAI H5N1 transmission directions, 18 had both a southward direction and a relatively high concentration. Differences between disease transmission and waterfowl migration directions were significantly smaller for autumn than for spring migration. The four northward transmission directions were found along Asian flyways, where the initial epicenter of the virus was located. We suggest waterfowl first picked up the virus from East Asia, then brought it to the north via spring migration, and then spread it to other parts of world mainly by autumn migration. We emphasize waterfowl autumn migration plays a relatively important role in HPAI H5N1 transmission compared to spring migration. PMID:27507581

  13. Highly Pathogenic Avian Influenza Virus A/H5N1 Infection in Vaccinated Meat Duck Flocks in the Mekong Delta of Vietnam.

    PubMed

    Cuong, N V; Truc, V N T; Nhung, N T; Thanh, T T; Chieu, T T B; Hieu, T Q; Men, N T; Mai, H H; Chi, H T; Boni, M F; van Doorn, H R; Thwaites, G E; Carrique-Mas, J J; Hoa, N T

    2016-04-01

    We investigated episodes of suspected highly pathogenic avian influenza (HPAI)-like illness among 12 meat duck flocks in two districts in Tien Giang province (Mekong Delta, Vietnam) in November 2013. In total, duck samples from 8 of 12 farms tested positive for HPAI virus subtype A/haemagglutinin 5 and neuraminidase 1 (H5N1) by real-time RT-PCR. Sequencing results confirmed clade of 2.3.2.1.c as the cause of the outbreaks. Most (7/8) laboratory-confirmed positive flocks had been vaccinated with inactivated HPAI H5N1 clade 2.3.4 vaccines <6 days prior to onset of clinical signs. A review of vaccination data in relation to estimated production in the area suggested that vaccination efforts were biased towards larger flocks and that vaccination coverage was low [21.2% ducks vaccinated with two shots (range by district 7.4-34.9%)]. The low-coverage data, the experimental evidence of lack of cross-protection conferred by the currently used vaccines based on clade 2.3.4 together with the short lifespan of meat duck flocks (60-70 days), suggest that vaccination is not likely to be effective as a tool for control of H5N1 infection in meat duck flocks in the area. PMID:26748550

  14. Quantitative assessment of a spatial multicriteria model for highly pathogenic avian influenza H5N1 in Thailand, and application in Cambodia

    PubMed Central

    Paul, Mathilde C.; Goutard, Flavie L.; Roulleau, Floriane; Holl, Davun; Thanapongtharm, Weerapong; Roger, François L.; Tran, Annelise

    2016-01-01

    The Highly Pathogenic Avian Influenza H5N1 (HPAI) virus is now considered endemic in several Asian countries. In Cambodia, the virus has been circulating in the poultry population since 2004, with a dramatic effect on farmers’ livelihoods and public health. In Thailand, surveillance and control are still important to prevent any new H5N1 incursion. Risk mapping can contribute effectively to disease surveillance and control systems, but is a very challenging task in the absence of reliable disease data. In this work, we used spatial multicriteria decision analysis (MCDA) to produce risk maps for HPAI H5N1 in poultry. We aimed to i) evaluate the performance of the MCDA approach to predict areas suitable for H5N1 based on a dataset from Thailand, comparing the predictive capacities of two sources of a priori knowledge (literature and experts), and ii) apply the best method to produce a risk map for H5N1 in poultry in Cambodia. Our results showed that the expert-based model had a very high predictive capacity in Thailand (AUC = 0.97). Applied in Cambodia, MCDA mapping made it possible to identify hotspots suitable for HPAI H5N1 in the Tonlé Sap watershed, around the cities of Battambang and Kampong Cham, and along the Vietnamese border. PMID:27489997

  15. Epidemiological and Evolutionary Inference of the Transmission Network of the 2014 Highly Pathogenic Avian Influenza H5N2 Outbreak in British Columbia, Canada

    PubMed Central

    Xu, Wanhong; Berhane, Yohannes; Dubé, Caroline; Liang, Binhua; Pasick, John; VanDomselaar, Gary; Alexandersen, Soren

    2016-01-01

    The first North American outbreak of highly pathogenic avian influenza (HPAI) involving a virus of Eurasian A/goose/Guangdong/1/1996 (H5N1) lineage began in the Fraser Valley of British Columbia, Canada in late November 2014. A total of 11 commercial and 1 non-commercial (backyard) operations were infected before the outbreak was terminated. Control measures included movement restrictions that were placed on a total of 404 individual premises, 150 of which were located within a 3 km radius of an infected premise(s) (IP). A complete epidemiological investigation revealed that the source of this HPAI H5N2 virus for 4 of the commercial IPs and the single non-commercial IP likely involved indirect contact with wild birds. Three IPs were associated with the movement of birds or service providers and localized/environmental spread was suspected as the source of infection for the remaining 4 IPs. Viral phylogenies, as determined by Bayesian Inference and Maximum Likelihood methods, were used to validate the epidemiologically inferred transmission network. The phylogenetic clustering of concatenated viral genomes and the median-joining phylogenetic network of the viruses supported, for the most part, the transmission network that was inferred by the epidemiologic analysis. PMID:27489095

  16. Role of vaccination-induced immunity and antigenic distance in the transmission dynamics of highly pathogenic avian influenza H5N1.

    PubMed

    Sitaras, Ioannis; Rousou, Xanthoula; Kalthoff, Donata; Beer, Martin; Peeters, Ben; de Jong, Mart C M

    2016-01-01

    Highly pathogenic avian influenza (HPAI) H5N1 epidemics in poultry cause huge economic losses as well as sporadic human morbidity and mortality. Vaccination in poultry has often been reported as being ineffective in preventing transmission and as a potential driving force in the selection of immune escape mutants. We conducted transmission experiments to evaluate the transmission dynamics of HPAI H5N1 strains in chickens vaccinated with high and low doses of immune escape mutants we have previously selected, and analysed the data using mathematical models. Remarkably, we demonstrate that the effect of antigenic distances between the vaccine and challenge strains used in this study is too small to influence the transmission dynamics of the strains used. This is because the effect of a sufficient vaccine dose on antibody levels against the challenge viruses is large enough to compensate for any decrease in antibody titres due to antigenic differences between vaccine and challenge strains. Our results show that at least under experimental conditions, vaccination will remain effective even after antigenic changes as may be caused by the initial selection in vaccinated birds. PMID:26763336

  17. Quantitative assessment of a spatial multicriteria model for highly pathogenic avian influenza H5N1 in Thailand, and application in Cambodia.

    PubMed

    Paul, Mathilde C; Goutard, Flavie L; Roulleau, Floriane; Holl, Davun; Thanapongtharm, Weerapong; Roger, François L; Tran, Annelise

    2016-01-01

    The Highly Pathogenic Avian Influenza H5N1 (HPAI) virus is now considered endemic in several Asian countries. In Cambodia, the virus has been circulating in the poultry population since 2004, with a dramatic effect on farmers' livelihoods and public health. In Thailand, surveillance and control are still important to prevent any new H5N1 incursion. Risk mapping can contribute effectively to disease surveillance and control systems, but is a very challenging task in the absence of reliable disease data. In this work, we used spatial multicriteria decision analysis (MCDA) to produce risk maps for HPAI H5N1 in poultry. We aimed to i) evaluate the performance of the MCDA approach to predict areas suitable for H5N1 based on a dataset from Thailand, comparing the predictive capacities of two sources of a priori knowledge (literature and experts), and ii) apply the best method to produce a risk map for H5N1 in poultry in Cambodia. Our results showed that the expert-based model had a very high predictive capacity in Thailand (AUC = 0.97). Applied in Cambodia, MCDA mapping made it possible to identify hotspots suitable for HPAI H5N1 in the Tonlé Sap watershed, around the cities of Battambang and Kampong Cham, and along the Vietnamese border. PMID:27489997

  18. Flying over an infected landscape: distribution of highly pathogenic avian influenza H5N1 risk in South Asia and satellite tracking of wild waterfowl

    USGS Publications Warehouse

    Gilbert, Marius; Newman, Scott H.; Takekawa, John Y.; Loth, Leo; Biradar, Chandrashekhar; Prosser, Diann J.; Balachandran, Sivananinthaperumal; Rao, Mandava Venkata Subba; Mundkur, Taej; Yan, Baoping; Xing, Zhi; Hou, Yuansheng; Batbayar, Nyambayar; Tseveenmayadag, Natsagdorj; Hogerwerf, Lenny; Slingenbergh, Jan; Xiao, Xiangming

    2010-01-01

    Highly pathogenic avian influenza (HPAI) H5N1 virus persists in Asia, posing a threat to poultry, wild birds, and humans. Previous work in Southeast Asia demonstrated that HPAI H5N1 risk is related to domestic ducks and people. Other studies discussed the role of migratory birds in the long distance spread of HPAI H5N1. However, the interplay between local persistence and long-distance dispersal has never been studied. We expand previous geospatial risk analysis to include South and Southeast Asia, and integrate the analysis with migration data of satellite-tracked wild waterfowl along the Central Asia flyway. We find that the population of domestic duck is the main factor delineating areas at risk of HPAI H5N1 spread in domestic poultry in South Asia, and that other risk factors, such as human population and chicken density, are associated with HPAI H5N1 risk within those areas. We also find that satellite tracked birds (Ruddy Shelduck and two Bar-headed Geese) reveal a direct spatio-temporal link between the HPAI H5N1 hot-spots identified in India and Bangladesh through our risk model, and the wild bird outbreaks in May,June,July 2009 in China(Qinghai Lake), Mongolia, and Russia. This suggests that the continental-scale dynamics of HPAI H5N1 are structured as a number of persistence areas delineated by domestic ducks, connected by rare transmission through migratory waterfowl.

  19. Southward autumn migration of waterfowl facilitates cross-continental transmission of the highly pathogenic avian influenza H5N1 virus

    NASA Astrophysics Data System (ADS)

    Xu, Yanjie; Gong, Peng; Wielstra, Ben; Si, Yali

    2016-08-01

    The highly pathogenic avian influenza subtype H5N1 (HPAI H5N1) is a worldwide zoonotic infectious disease, threatening humans, poultry and wild birds. The role of wild birds in the spread of HPAI H5N1 has previously been investigated by comparing disease spread patterns with bird migration routes. However, the different roles that the southward autumn and northward spring migration might play in virus transmission have hardly been explored. Using direction analysis, we analyze HPAI H5N1 transmission directions and angular concentration of currently circulating viral clades, and compare these with waterfowl seasonal migration directions along major waterfowl flyways. Out of 22 HPAI H5N1 transmission directions, 18 had both a southward direction and a relatively high concentration. Differences between disease transmission and waterfowl migration directions were significantly smaller for autumn than for spring migration. The four northward transmission directions were found along Asian flyways, where the initial epicenter of the virus was located. We suggest waterfowl first picked up the virus from East Asia, then brought it to the north via spring migration, and then spread it to other parts of world mainly by autumn migration. We emphasize waterfowl autumn migration plays a relatively important role in HPAI H5N1 transmission compared to spring migration.

  20. Phylodynamics of H5N1 Highly Pathogenic Avian Influenza in Europe, 2005–2010: Potential for Molecular Surveillance of New Outbreaks

    PubMed Central

    Alkhamis, Mohammad A.; Moore, Brian R.; Perez, Andres M.

    2015-01-01

    Previous Bayesian phylogeographic studies of H5N1 highly pathogenic avian influenza viruses (HPAIVs) explored the origin and spread of the epidemic from China into Russia, indicating that HPAIV circulated in Russia prior to its detection there in 2005. In this study, we extend this research to explore the evolution and spread of HPAIV within Europe during the 2005–2010 epidemic, using all available sequences of the hemagglutinin (HA) and neuraminidase (NA) gene regions that were collected in Europe and Russia during the outbreak. We use discrete-trait phylodynamic models within a Bayesian statistical framework to explore the evolution of HPAIV. Our results indicate that the genetic diversity and effective population size of HPAIV peaked between mid-2005 and early 2006, followed by drastic decline in 2007, which coincides with the end of the epidemic in Europe. Our results also suggest that domestic birds were the most likely source of the spread of the virus from Russia into Europe. Additionally, estimates of viral dispersal routes indicate that Russia, Romania, and Germany were key epicenters of these outbreaks. Our study quantifies the dynamics of a major European HPAIV pandemic and substantiates the ability of phylodynamic models to improve molecular surveillance of novel AIVs. PMID:26110587