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
Influenza A virus(IAV)continues to pose a pandemic threat to public health,resulting a high mortality rate annually and during pandemic years.Posttranslational modification of viral protein plays a substantial role in...Influenza A virus(IAV)continues to pose a pandemic threat to public health,resulting a high mortality rate annually and during pandemic years.Posttranslational modification of viral protein plays a substantial role in regulating IAV infection.Here,based on immunoprecipitation(IP)-based mass spectrometry(MS)and purified virus-coupled MS,a total of 89 phosphorylation sites distributed among 10 encoded viral proteins of IAV were identified,including 60 novel phosphorylation sites.Additionally,for the first time,we provide evidence that PB2 can also be acetylated at site K187.Notably,the PB2 S181 phosphorylation site was consistently identified in both IP-based MS and purified virus-based MS.Both S181 and K187 are exposed on the surface of the PB2 protein and are highly conserved in various IAV strains,suggesting their fundamental importance in the IAV life cycle.Bioinformatic analysis results demonstrated that S181E/A and K187Q/R mimic mutations do not significantly alter the PB2 protein structure.While continuous phosphorylation mimicked by the PB2 S181E mutation substantially decreases viral fitness in mice,PB2 K187Q mimetic acetylation slightly enhances viral virulence in mice.Mechanistically,PB2 S181E substantially impairs viral polymerase activity and viral replication,remarkably dampens protein stability and nuclear accumulation of PB2,and significantly weakens IAV-induced inflammatory responses.Therefore,our study further enriches the database of phosphorylation and acetylation sites of influenza viral proteins,laying a foundation for subsequent mechanistic studies.Meanwhile,the unraveled antiviral effect of PB2 S181E mimetic phosphorylation may provide a new target for the subsequent study of antiviral drugs.展开更多
Decades have passed since the first discovery of H10-subtype avian influenza virus(AIV) in chickens in 1949,and it has been detected in many species including mammals such as minks,pigs,seals and humans.Cases of human...Decades have passed since the first discovery of H10-subtype avian influenza virus(AIV) in chickens in 1949,and it has been detected in many species including mammals such as minks,pigs,seals and humans.Cases of human infections with H10N8viruses identified in China in 2013 have raised widespread attention.Two novel reassortant H10N3 viruses were isolated from chickens in December 2019 in eastern China during routine surveillance for AIVs.The internal genes of these viruses were derived from genotype S(G57) H9N2 and were consistent with H5N6,H7N9 and H10N8,which cause fatal infections in humans.Their viral pathogenicity and transmissibility were further studied in different animal models.The two H10N3 isolates had low pathogenicity in chickens and were transmitted between chickens via direct contact.These viruses were highly pathogenic in mice and could be transmitted between guinea pigs via direct contact and respiratory droplets.More importantly,these viruses can bind to both human-type SAα-2,6-Gal receptors and avian-type SAα-2,3-Gal receptors.Asymptomatic shedding in chickens and good adaptability to mammals of these H10N3 isolates would make it easier to transmit to humans and pose a threat to public health.展开更多
Dear Editor,Newcastle disease(ND),caused by virulent Newcastle disease virus(NDV),is a highly contagious and economically devastating viral disease of birds(Habib et al.2018).NDV,also termed as avian paramyxovirus typ...Dear Editor,Newcastle disease(ND),caused by virulent Newcastle disease virus(NDV),is a highly contagious and economically devastating viral disease of birds(Habib et al.2018).NDV,also termed as avian paramyxovirus type 1(APMV-1),belongs to the genus Orthoavulavirus in the family Paramyxoviridae according to the International Committee on Taxonomy of Viruses(ICTV)(Amarasinghe et al.2019).According to the latest phylogenetic classification system.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.
基金supported by the National Natural Science Foundation of China(32072832,32372976)by the National Key Research and Development Project of China(2021YFD1800202)+3 种基金by Jiangsu Province Agricultural Science&Technology Independent Innovation Funds[CX(21)3141]by the Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX22_3553 and KYCX21_3277)by the Earmarked Fund for China Agriculture Research System(CARS-40)a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Influenza A virus(IAV)continues to pose a pandemic threat to public health,resulting a high mortality rate annually and during pandemic years.Posttranslational modification of viral protein plays a substantial role in regulating IAV infection.Here,based on immunoprecipitation(IP)-based mass spectrometry(MS)and purified virus-coupled MS,a total of 89 phosphorylation sites distributed among 10 encoded viral proteins of IAV were identified,including 60 novel phosphorylation sites.Additionally,for the first time,we provide evidence that PB2 can also be acetylated at site K187.Notably,the PB2 S181 phosphorylation site was consistently identified in both IP-based MS and purified virus-based MS.Both S181 and K187 are exposed on the surface of the PB2 protein and are highly conserved in various IAV strains,suggesting their fundamental importance in the IAV life cycle.Bioinformatic analysis results demonstrated that S181E/A and K187Q/R mimic mutations do not significantly alter the PB2 protein structure.While continuous phosphorylation mimicked by the PB2 S181E mutation substantially decreases viral fitness in mice,PB2 K187Q mimetic acetylation slightly enhances viral virulence in mice.Mechanistically,PB2 S181E substantially impairs viral polymerase activity and viral replication,remarkably dampens protein stability and nuclear accumulation of PB2,and significantly weakens IAV-induced inflammatory responses.Therefore,our study further enriches the database of phosphorylation and acetylation sites of influenza viral proteins,laying a foundation for subsequent mechanistic studies.Meanwhile,the unraveled antiviral effect of PB2 S181E mimetic phosphorylation may provide a new target for the subsequent study of antiviral drugs.
基金supported by the National Key Research and Development Project of China (2016YFD0500202-1,2016YFD0501601)the National Natural Science Foundation of China(31772755)+3 种基金Jiangsu Provincial Natural Science Fund for Excellent Young Scholars (BK20170068)the Earmarked Fund For China Agriculture Research System (CARS-40)the Open Project Program of Jiangsu Key Laboratory of Zoonosis (R1808)the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)。
文摘Decades have passed since the first discovery of H10-subtype avian influenza virus(AIV) in chickens in 1949,and it has been detected in many species including mammals such as minks,pigs,seals and humans.Cases of human infections with H10N8viruses identified in China in 2013 have raised widespread attention.Two novel reassortant H10N3 viruses were isolated from chickens in December 2019 in eastern China during routine surveillance for AIVs.The internal genes of these viruses were derived from genotype S(G57) H9N2 and were consistent with H5N6,H7N9 and H10N8,which cause fatal infections in humans.Their viral pathogenicity and transmissibility were further studied in different animal models.The two H10N3 isolates had low pathogenicity in chickens and were transmitted between chickens via direct contact.These viruses were highly pathogenic in mice and could be transmitted between guinea pigs via direct contact and respiratory droplets.More importantly,these viruses can bind to both human-type SAα-2,6-Gal receptors and avian-type SAα-2,3-Gal receptors.Asymptomatic shedding in chickens and good adaptability to mammals of these H10N3 isolates would make it easier to transmit to humans and pose a threat to public health.
基金This work was supported by grants from the National Key Research and Development Program of China(2017YFD0500101-3,2017YFD0500802)the National Natural Science Foundation of China(31873021),the National Key Technology R&D Program of China(2015BAD12B03)+2 种基金the Earmarked Fund for China Agriculture Research System(CARS-40)the National Key Research and Development Program of China(2017YFD0500702)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Dear Editor,Newcastle disease(ND),caused by virulent Newcastle disease virus(NDV),is a highly contagious and economically devastating viral disease of birds(Habib et al.2018).NDV,also termed as avian paramyxovirus type 1(APMV-1),belongs to the genus Orthoavulavirus in the family Paramyxoviridae according to the International Committee on Taxonomy of Viruses(ICTV)(Amarasinghe et al.2019).According to the latest phylogenetic classification system.