H7N9 subtype avian influenza virus poses a great challenge for poultry industry.Newcastle disease virus(NDV)-vectored H7N9 avian influenza vaccines(NDV_(vec)H7N9)are effective in disease control because they are prote...H7N9 subtype avian influenza virus poses a great challenge for poultry industry.Newcastle disease virus(NDV)-vectored H7N9 avian influenza vaccines(NDV_(vec)H7N9)are effective in disease control because they are protective and allow mass administration.Of note,these vaccines elicit undetectable H7N9-specific hemagglutination-inhibition(HI)but high IgG antibodies in chickens.However,the molecular basis and protective mechanism underlying this particular antibody immunity remain unclear.Herein,immunization with an NDV_(vec)H7N9 induced low anti-H7N9 HI and virus neutralization titers but high levels of hemagglutinin(HA)-binding IgG antibodies in chickens.Three residues(S150,G151 and S152)in HA of H7N9 virus were identified as the dominant epitopes recognized by the NDV_(vec)H7N9 immune serum.Passively transferred NDV_(vec)H7N9 immune serum conferred complete protection against H7N9 virus infection in chickens.The NDV_(vec)H7N9 immune serum can mediate a potent lysis of HA-expressing and H7N9 virus-infected cells and significantly suppress H7N9 virus infectivity.These activities of the serum were significantly impaired after heat-inactivation or treatment with complement inhibitor,suggesting the engagement of the complement system.Moreover,mutations in the 150-SGS-152 sites in HA resulted in significant reductions in cell lysis and virus neutralization mediated by the NDV_(vec)H7N9 immune serum,indicating the requirement of antibody-antigen binding for complement activity.Therefore,antibodies induced by the NDV_(vec)H7N9 can activate antibody-dependent complement-mediated lysis of H7N9 virus-infected cells and complement-mediated neutralization of H7N9 virus.Our findings unveiled a novel role of the complement in protection conferred by the NDV_(vec)H7N9,highlighting a potential benefit of engaging the complement system in H7N9 vaccine design.展开更多
The relentless march of a highly pathogenic avian influenza virus(HPAIV)strain,known as H5N1,to become an unprecedented panzootic continues unchecked.The leap of H5N1 clade 2.3.4.4b from Eurasia and Africa to North Am...The relentless march of a highly pathogenic avian influenza virus(HPAIV)strain,known as H5N1,to become an unprecedented panzootic continues unchecked.The leap of H5N1 clade 2.3.4.4b from Eurasia and Africa to North America in 2021 and its further spread to South America and the Antarctic have exposed new avian and mammalian populations to the virus and led to outbreaks on an unrivaled scale.The virus has infected wild birds across vast geographic regions and caused wildlife deaths in some of the world's most biodiverse ecosystems.展开更多
Highly pathogenic avian influenza(HPAI)H5N1 hemagglutinin clade 2.3.4.4b was detected in the United States in 2021.These HPAI viruses caused mortality events in poultry,wild birds,and wild mammals.On March 25,2024,HPA...Highly pathogenic avian influenza(HPAI)H5N1 hemagglutinin clade 2.3.4.4b was detected in the United States in 2021.These HPAI viruses caused mortality events in poultry,wild birds,and wild mammals.On March 25,2024,HPAI H5N1 clade 2.3.4.4b was confirmed in a dairy cow in Texas in response to a multi-state investigation into milk production losses.1 Over 200 positive herds were identified in 14 U.S.states.The case description included reduced feed intake and rumen motility in lactating cows,decreased milk production,and thick yellow milk.2,3 The diagnostic investigation revealed viral RNA in milk and mammary tissue with alveolar epithelial degeneration and necrosis and positive immunoreactivity of glandular epithelium.A single transmission event,likely from birds,was followed by limited local transmission and onward horizontal transmission of H5N1 clade 2.3.4.4b genotype B3.13.4 We sought to experimentally reproduce infection with genotype B3.13 in Holstein yearling heifers and lactating cows.Heifers were inoculated by aerosol respiratory route and cows by intramammary route.Clinical disease was mild in heifers,but infection was confirmed by virus detection,lesions,and seroconversion.Clinical disease in lactating cows included decreased rumen motility,changes to milk appearance,and production losses.Infection was confirmed by high levels of viral RNA detected in milk,virus isolation,lesions in mammary tissue,and seroconversion.This study provides the foundation to investigate additional routes of infection,pathogenesis,transmission,and intervention strategies.展开更多
基金supported by the earmarked fund for China Agriculture Research System(CARS-40)the Key Research and Development Project of Yangzhou(Modern Agriculture),China(YZ2022052)the‘‘High-end Talent Support Program’’of Yangzhou University,China。
文摘H7N9 subtype avian influenza virus poses a great challenge for poultry industry.Newcastle disease virus(NDV)-vectored H7N9 avian influenza vaccines(NDV_(vec)H7N9)are effective in disease control because they are protective and allow mass administration.Of note,these vaccines elicit undetectable H7N9-specific hemagglutination-inhibition(HI)but high IgG antibodies in chickens.However,the molecular basis and protective mechanism underlying this particular antibody immunity remain unclear.Herein,immunization with an NDV_(vec)H7N9 induced low anti-H7N9 HI and virus neutralization titers but high levels of hemagglutinin(HA)-binding IgG antibodies in chickens.Three residues(S150,G151 and S152)in HA of H7N9 virus were identified as the dominant epitopes recognized by the NDV_(vec)H7N9 immune serum.Passively transferred NDV_(vec)H7N9 immune serum conferred complete protection against H7N9 virus infection in chickens.The NDV_(vec)H7N9 immune serum can mediate a potent lysis of HA-expressing and H7N9 virus-infected cells and significantly suppress H7N9 virus infectivity.These activities of the serum were significantly impaired after heat-inactivation or treatment with complement inhibitor,suggesting the engagement of the complement system.Moreover,mutations in the 150-SGS-152 sites in HA resulted in significant reductions in cell lysis and virus neutralization mediated by the NDV_(vec)H7N9 immune serum,indicating the requirement of antibody-antigen binding for complement activity.Therefore,antibodies induced by the NDV_(vec)H7N9 can activate antibody-dependent complement-mediated lysis of H7N9 virus-infected cells and complement-mediated neutralization of H7N9 virus.Our findings unveiled a novel role of the complement in protection conferred by the NDV_(vec)H7N9,highlighting a potential benefit of engaging the complement system in H7N9 vaccine design.
文摘The relentless march of a highly pathogenic avian influenza virus(HPAIV)strain,known as H5N1,to become an unprecedented panzootic continues unchecked.The leap of H5N1 clade 2.3.4.4b from Eurasia and Africa to North America in 2021 and its further spread to South America and the Antarctic have exposed new avian and mammalian populations to the virus and led to outbreaks on an unrivaled scale.The virus has infected wild birds across vast geographic regions and caused wildlife deaths in some of the world's most biodiverse ecosystems.
文摘Highly pathogenic avian influenza(HPAI)H5N1 hemagglutinin clade 2.3.4.4b was detected in the United States in 2021.These HPAI viruses caused mortality events in poultry,wild birds,and wild mammals.On March 25,2024,HPAI H5N1 clade 2.3.4.4b was confirmed in a dairy cow in Texas in response to a multi-state investigation into milk production losses.1 Over 200 positive herds were identified in 14 U.S.states.The case description included reduced feed intake and rumen motility in lactating cows,decreased milk production,and thick yellow milk.2,3 The diagnostic investigation revealed viral RNA in milk and mammary tissue with alveolar epithelial degeneration and necrosis and positive immunoreactivity of glandular epithelium.A single transmission event,likely from birds,was followed by limited local transmission and onward horizontal transmission of H5N1 clade 2.3.4.4b genotype B3.13.4 We sought to experimentally reproduce infection with genotype B3.13 in Holstein yearling heifers and lactating cows.Heifers were inoculated by aerosol respiratory route and cows by intramammary route.Clinical disease was mild in heifers,but infection was confirmed by virus detection,lesions,and seroconversion.Clinical disease in lactating cows included decreased rumen motility,changes to milk appearance,and production losses.Infection was confirmed by high levels of viral RNA detected in milk,virus isolation,lesions in mammary tissue,and seroconversion.This study provides the foundation to investigate additional routes of infection,pathogenesis,transmission,and intervention strategies.