Objective In China, 24 cases of human infection with highly pathogenic avian influenza(HPAI) H5 N6 virus have been confirmed since the first confirmed case in 2014. Therefore, we developed and assessed two H5 N6 candi...Objective In China, 24 cases of human infection with highly pathogenic avian influenza(HPAI) H5 N6 virus have been confirmed since the first confirmed case in 2014. Therefore, we developed and assessed two H5 N6 candidate vaccine viruses(CVVs).Methods In accordance with the World Health Organization(WHO) recommendations, we constructed two reassortant viruses using reverse genetics(RG) technology to match the two different epidemic H5 N6 viruses. We performed complete genome sequencing to determine the genetic stability. We assessed the growth ability of the studied viruses in MDCK cells and conducted a hemagglutination inhibition assay to analyze their antigenicity. Pathogenicity attenuation was also evaluated in vitro and in vivo.Results The results showed that no mutations occurred in hemagglutinin or neuraminidase, and both CVVs retained their original antigenicity. The replication capacity of the two CVVs reached a level similar to that of A/Puerto Rico/8/34 in MDCK cells. The two CVVs showed low pathogenicity in vitro and in vivo, which are in line with the WHO requirements for CVVs.Conclusion We obtained two genetically stable CVVs of HPAI H5N6 with high growth characteristics,which may aid in our preparedness for a potential H5N6 pandemic.展开更多
To evaluate the risk of highly pathogenic avian influenza (HPAI) in China's Mainland, a risk assessment framework was built. Risk factors were determined by analyzing the epidemic data using the brainstorming me...To evaluate the risk of highly pathogenic avian influenza (HPAI) in China's Mainland, a risk assessment framework was built. Risk factors were determined by analyzing the epidemic data using the brainstorming method; the analytic hierarchy process was designed to weigh risk factors, and the integrated multicriteria analysis was used to evaluate the final result. The completed framework included the risk factor system, data standards for risk factors, weights of risk factors, and integrated assessment methods. This risk assessment framework can be used to quantitatively analyze the outbreak and spread of HPAI in China's Mainland.展开更多
The highly pathogenic avian influenza (HPAI) H5N1 virus has caused several outbreaks in domestic poultry. Despite great efforts to control the spread of this virus, it continues to evolve and poses a substantial thr...The highly pathogenic avian influenza (HPAI) H5N1 virus has caused several outbreaks in domestic poultry. Despite great efforts to control the spread of this virus, it continues to evolve and poses a substantial threat to public health because of a high mortality rate. In this study, we sequenced whole genomes of eight H5N1 avian influenza viruses isolated from domestic poultry in eastern China and compared them with those of typical influenza virus strains. Phylogenetic analyses showed that all eight genomes belonged to clade 2.3.2.1 and clade 7.2, the two main circulating clades in China. Viruses that clustered in clade 2.3.2.1 shared a high degree of homology with H5N1 isolates located in eastern Asian. Isolates that clustered in clade 7.2 were found to circulate throughout China, with an east-to-west density gradient. Pathogenicity studies in mice showed that these isolates replicate in the lungs, and clade 2.3.2.1 viruses exhibit a notably higher degree of virulence compared to clade 7.2 viruses. Our results contribute to the elucidation of the biological characterization and pathogenicity of HPAI H5N1 viruses.展开更多
The highly pathogenic influenza A virus subtype H5N1 spread throughout Asia since 2003, reached to Europe in 2005, and the Middle East, as well as Africa and caused a global concern for a potential pandemic threat las...The highly pathogenic influenza A virus subtype H5N1 spread throughout Asia since 2003, reached to Europe in 2005, and the Middle East, as well as Africa and caused a global concern for a potential pandemic threat last decade. A Clade 2.3.2 H5N1 virus became dominate in the Qinghai Lake region in 2009 with sporadic mammal cases of infection and transferred to Russia and Europe through wild migratory birds. Currently, HPAI H5N1 of clades 2.3.4, 2.3.2, and 7 are the dominant co-circulating H5N1 viruses in poultry in Asia. 2.3.2 Clade is dominant in wild birds through the world whereas there is no evident data about Clade 7 circulation in wild birds. We detected HPAI H5N1 virus of Clade 7.1 in Qinghai Lake, that closely related to Shanxi-like and Vietnam viruses co-circulating in poultry. This is the first report of Clade 7.1 H5N1 in wild birds. Based on phylogenetic analyses, the virus can be originated from Clade 7.1 virus gene pool that spread in Vietnam and Chinese poultry and could spread with migratory birds to Qinghai Lake. The Qinghai Lake continues to be significant hotspot for H5N1 surveillance since the regular outbreaks occurred there in wild birds and mammals. Based on these facts and findings, the related researchers should pay more attention to the Qinghai Lake basin as significant hotspot for H5N1 avian influenza surveillance since the regular H5N1 outbreaks occurred there in wild birds with sporadic mammal cases of infection.展开更多
A novel Clade 2.3.2.1c H5N1 reassortant virus caused several outbreaks in wild birds in some regions of China from late 2014 to 2015.Based on the genetic and phylogenetic analyses,the viruses possess a stable gene con...A novel Clade 2.3.2.1c H5N1 reassortant virus caused several outbreaks in wild birds in some regions of China from late 2014 to 2015.Based on the genetic and phylogenetic analyses,the viruses possess a stable gene constellation with a Clade 2.3.2.1c HA,a H9N2-derived PB2 gene and the other six genes of Asian H5N1-origin.The Clade 2.3.2.1c H5N1 reassortants displayed a high genetic relationship to a human H5N1 strain(A/Alberta/01/2014).Further analysis showed that similar viruses have been circulating in wild birds in China,Russia,Dubai(Western Asia),Bulgaria and Romania(Europe),as well as domestic poultry in some regions of Africa.The affected areas include the Central Asian,East Asian-Australasian,West Asian-East African,and Black Sea/Mediterranean flyways.These results show that the novel Clade 2.3.2.1c reassortant viruses are circulating worldwide and may have gained a selective advantage in migratory birds,thus posing a serious threat to wild birds and potentially humans.展开更多
Every year billions of chickens are shipped thousands of miles around the globe in order to meet the ever increasing demands for this cheap and nutritious protein source.Unfortunately,transporting chickens internation...Every year billions of chickens are shipped thousands of miles around the globe in order to meet the ever increasing demands for this cheap and nutritious protein source.Unfortunately,transporting chickens internationally can also increase the chance for introducing zoonotic viruses,such as highly pathogenic avian influenza A(H5N1)to new countries.Our study used a retrospective analysis of poultry trading data from 2003 through 2011 to assess the risk of H5N1 poultry infection in an importing country.We found that the risk of infection in an importing country increased by a factor of 1.3(95%CI:1.1e1.5)for every 10-fold increase in live chickens imported from countries experiencing at least one H5N1 poultry case during that year.These results suggest that the risk in a particular country can be significantly reduced if imports from countries experiencing an outbreak are decreased during the year of infection or if biosecurity measures such as screening,vaccination,and infection control practices are increased.These findings show that limiting trade of live chickens or increasing infection control practices during contagious periods may be an important step in reducing the spread of H5N1 and other emerging avian influenza viruses.展开更多
Bird infections with highly pathogenic avian influenza A(H5N6) viruses have been identified since 2014. With very limited occasion, the virus could sporadically spilled over to infect humans. It has been recognized th...Bird infections with highly pathogenic avian influenza A(H5N6) viruses have been identified since 2014. With very limited occasion, the virus could sporadically spilled over to infect humans. It has been recognized that all human infections were within southern region of China's Mainland until the case reported here in Beijing in Aug. 2019. This was the first human case infected with highly pathogenic avian influenza A(H5N6) virus in northern China. The infection was confirmed by real-time RT-PCR assay. The whole genome sequences were obtained from clinical sample. Genetic characteristics of the virus were identified similar to those of previous avian influenza A(H5N6) viruses, retaining the main features of the avian influenza virus.展开更多
As part of the USA’s National Strategy for Pandemic Influenza,an Interagency Strategic Plan for the Early Detection of Highly Pathogenic H5N1 Avian Influenza in Wild Migratory Birds was developed and implemented.From...As part of the USA’s National Strategy for Pandemic Influenza,an Interagency Strategic Plan for the Early Detection of Highly Pathogenic H5N1 Avian Influenza in Wild Migratory Birds was developed and implemented.From1April2006 through 31 March 2009,261946 samples fromwild birds and 101457 wild bird fecalsamples were collected in the USA;no highly pathogenic avian influenza was detected.The United States Department of Agriculture,and state and tribal cooperators accounted for 213115(81%)of the wild bird samples collected;31,27,21 and 21%of the samples were collected from theAtlantic,Pacific,Central and Mississippi flyways,respectively.More than 250 species of wild birds in all 50 states were sampled.The majority of wild birds(86%)were dabbling ducks,geese,swans and shorebirds.The apparent prevalence of low pathogenic avian influenza viruses during biological years 2007 and 2008 was 9.7 and 11.0%,respectively.The apparent prevalence of H5 and H7 subtypes across all species sampled were 0.5 and 0.06%,respectively.The pooled fecal samples(n=101539)positive for low pathogenic avian influenza were 4.0,6.7 and 4.7%for biological years 2006,2007 and 2008,respectively.The highly pathogenic early detection system for wild birds developed and implemented in the USA represents the largest coordinated wildlife disease surveillance system ever conducted.This effort provided evidence that wild birds in the USA were free of highly pathogenic avian influenza virus(given the expected minimum prevalence of 0.001%)at the 99.9%confidence level during the surveillance period.展开更多
Vaccination for highly pathogenic avian influenza(HPAI)has been implemented in China for a decade,however,the virus is still present in poultry.A series of recombinant vaccines,Re-1 to Re-7,have been developed and use...Vaccination for highly pathogenic avian influenza(HPAI)has been implemented in China for a decade,however,the virus is still present in poultry.A series of recombinant vaccines,Re-1 to Re-7,have been developed and used,and Re-8 will also be used in clinical settings to prevent the prevailing flu strains.The question remains,when can China eradicate the disease?Here,we review the epidemiology of H5 HPAI along with the development,usage and problems of vaccines.Further suggestions for controlling the disease in China are provided.展开更多
Highly pathogenic avian influenza (HPAI) contamination via wild birds and rodents poses a threat to food security and safety. As chicken meat comprises an increasing proportion of diet in China, it is useful to dete...Highly pathogenic avian influenza (HPAI) contamination via wild birds and rodents poses a threat to food security and safety. As chicken meat comprises an increasing proportion of diet in China, it is useful to determine whether broiler farmers are adopting wild bird and rodent controls to minimize the risk of HPAI impacts on food supply. Our study surveyed a cross sectional sample of 331 Chinese broiler farmers in six provinces. We find that only 47% of farmers (mainly farmers with large herds) adopted control measures against wild birds and rodents, while 14% adopted no measures. Farm size was the biggest driver of adoption followed by proportion of farm revenue derived from broiler production. However, southern farmers were at a far greater probability of non-adoption. We suggest that assistance in the form of education/training programs and subsidized traps or baiting controls across smaller producers could help raise of the adoption level toward more effective HPAI control.展开更多
Highly pathogenic avian influenza H5N 1 epidemics are a significant public health hazard. Genetically engineered H5N 1 viruses with mammalian transmission activity highlight the potential risk of a human influenza H5N...Highly pathogenic avian influenza H5N 1 epidemics are a significant public health hazard. Genetically engineered H5N 1 viruses with mammalian transmission activity highlight the potential risk of a human influenza H5N 1 pandemic. Understanding the underlying principles of the innate immune system in response to influenza H5N 1 viruses will lead to improved prevention and control of these potentially deadly viruses, γδT cells act as the first line of defense against microbial infection and help initiate adaptive immune responses during the early stages of viral infection. In this study, we investigated the molecular mechanisms of γδ T cells in response to influenza H5N1 viral infection, We found that recombinant hemagglutinin (rHA) derived from three different strains of influenza H5N 1 viruses elicited the activation of γδ T cells cultured in peripheral blood mononuclear cells (PBMCs). Both the cell surface expression of CD69, an early activation marker on γδ T cells, and the production of interferon-y (IFN-y) were significantly increased. Notably, the rHA protein-induced γδ T-cell activation was not mediated by TCRγδ, NKG2D or pattern recognition receptors (PRRs) or NKp46 receptors. The interaction of rHA proteins with sialic acid receptors may play a critical role in γδ T-cell activation. Our data may provide insight into the mechanisms underlyingγδT-cell activation in response to infection with H5N1 viruses.展开更多
基金This study was supported by the National Major Science and Technology Project for Control and Prevention of Major Infectious Diseases in China[No.2018ZX10711001,2018ZX10305409-004-002]Emergency Prevention and Control Project of Ministry of Science and Technology of China[No.10600100000015001206].
文摘Objective In China, 24 cases of human infection with highly pathogenic avian influenza(HPAI) H5 N6 virus have been confirmed since the first confirmed case in 2014. Therefore, we developed and assessed two H5 N6 candidate vaccine viruses(CVVs).Methods In accordance with the World Health Organization(WHO) recommendations, we constructed two reassortant viruses using reverse genetics(RG) technology to match the two different epidemic H5 N6 viruses. We performed complete genome sequencing to determine the genetic stability. We assessed the growth ability of the studied viruses in MDCK cells and conducted a hemagglutination inhibition assay to analyze their antigenicity. Pathogenicity attenuation was also evaluated in vitro and in vivo.Results The results showed that no mutations occurred in hemagglutinin or neuraminidase, and both CVVs retained their original antigenicity. The replication capacity of the two CVVs reached a level similar to that of A/Puerto Rico/8/34 in MDCK cells. The two CVVs showed low pathogenicity in vitro and in vivo, which are in line with the WHO requirements for CVVs.Conclusion We obtained two genetically stable CVVs of HPAI H5N6 with high growth characteristics,which may aid in our preparedness for a potential H5N6 pandemic.
文摘To evaluate the risk of highly pathogenic avian influenza (HPAI) in China's Mainland, a risk assessment framework was built. Risk factors were determined by analyzing the epidemic data using the brainstorming method; the analytic hierarchy process was designed to weigh risk factors, and the integrated multicriteria analysis was used to evaluate the final result. The completed framework included the risk factor system, data standards for risk factors, weights of risk factors, and integrated assessment methods. This risk assessment framework can be used to quantitatively analyze the outbreak and spread of HPAI in China's Mainland.
基金supported in part by the funding from the National Natural Scientific Foundation(81370518)the National High Technology Research and Development Program of China(2015AA020924 and 2013ZX10004003)supported by a grant from the Beijing Nova Program(No.Z141107001814054)
文摘The highly pathogenic avian influenza (HPAI) H5N1 virus has caused several outbreaks in domestic poultry. Despite great efforts to control the spread of this virus, it continues to evolve and poses a substantial threat to public health because of a high mortality rate. In this study, we sequenced whole genomes of eight H5N1 avian influenza viruses isolated from domestic poultry in eastern China and compared them with those of typical influenza virus strains. Phylogenetic analyses showed that all eight genomes belonged to clade 2.3.2.1 and clade 7.2, the two main circulating clades in China. Viruses that clustered in clade 2.3.2.1 shared a high degree of homology with H5N1 isolates located in eastern Asian. Isolates that clustered in clade 7.2 were found to circulate throughout China, with an east-to-west density gradient. Pathogenicity studies in mice showed that these isolates replicate in the lungs, and clade 2.3.2.1 viruses exhibit a notably higher degree of virulence compared to clade 7.2 viruses. Our results contribute to the elucidation of the biological characterization and pathogenicity of HPAI H5N1 viruses.
文摘The highly pathogenic influenza A virus subtype H5N1 spread throughout Asia since 2003, reached to Europe in 2005, and the Middle East, as well as Africa and caused a global concern for a potential pandemic threat last decade. A Clade 2.3.2 H5N1 virus became dominate in the Qinghai Lake region in 2009 with sporadic mammal cases of infection and transferred to Russia and Europe through wild migratory birds. Currently, HPAI H5N1 of clades 2.3.4, 2.3.2, and 7 are the dominant co-circulating H5N1 viruses in poultry in Asia. 2.3.2 Clade is dominant in wild birds through the world whereas there is no evident data about Clade 7 circulation in wild birds. We detected HPAI H5N1 virus of Clade 7.1 in Qinghai Lake, that closely related to Shanxi-like and Vietnam viruses co-circulating in poultry. This is the first report of Clade 7.1 H5N1 in wild birds. Based on phylogenetic analyses, the virus can be originated from Clade 7.1 virus gene pool that spread in Vietnam and Chinese poultry and could spread with migratory birds to Qinghai Lake. The Qinghai Lake continues to be significant hotspot for H5N1 surveillance since the regular outbreaks occurred there in wild birds and mammals. Based on these facts and findings, the related researchers should pay more attention to the Qinghai Lake basin as significant hotspot for H5N1 avian influenza surveillance since the regular H5N1 outbreaks occurred there in wild birds with sporadic mammal cases of infection.
基金supported by grants from the National Natural Science Foundation of China (31311120063,81470096,31570026,31471253)the Ministry of Education and Science of the Russian Federation (Chinese-Russian project:RFMEFI61315X0045)+3 种基金the intramural special grant for influenza virus research from the Chinese Academy of Sciences (KJZD-EW-L09)the IDRCAPEIR program (106915-001)Special Project of Ministry of Science and Technology (2013FY113500)supported by the “Taishan Scholar” project of Shandong Province
文摘A novel Clade 2.3.2.1c H5N1 reassortant virus caused several outbreaks in wild birds in some regions of China from late 2014 to 2015.Based on the genetic and phylogenetic analyses,the viruses possess a stable gene constellation with a Clade 2.3.2.1c HA,a H9N2-derived PB2 gene and the other six genes of Asian H5N1-origin.The Clade 2.3.2.1c H5N1 reassortants displayed a high genetic relationship to a human H5N1 strain(A/Alberta/01/2014).Further analysis showed that similar viruses have been circulating in wild birds in China,Russia,Dubai(Western Asia),Bulgaria and Romania(Europe),as well as domestic poultry in some regions of Africa.The affected areas include the Central Asian,East Asian-Australasian,West Asian-East African,and Black Sea/Mediterranean flyways.These results show that the novel Clade 2.3.2.1c reassortant viruses are circulating worldwide and may have gained a selective advantage in migratory birds,thus posing a serious threat to wild birds and potentially humans.
基金This work is sponsored in part by the Robert Wood Johnson Foundation Pioneer Grant 67919.
文摘Every year billions of chickens are shipped thousands of miles around the globe in order to meet the ever increasing demands for this cheap and nutritious protein source.Unfortunately,transporting chickens internationally can also increase the chance for introducing zoonotic viruses,such as highly pathogenic avian influenza A(H5N1)to new countries.Our study used a retrospective analysis of poultry trading data from 2003 through 2011 to assess the risk of H5N1 poultry infection in an importing country.We found that the risk of infection in an importing country increased by a factor of 1.3(95%CI:1.1e1.5)for every 10-fold increase in live chickens imported from countries experiencing at least one H5N1 poultry case during that year.These results suggest that the risk in a particular country can be significantly reduced if imports from countries experiencing an outbreak are decreased during the year of infection or if biosecurity measures such as screening,vaccination,and infection control practices are increased.These findings show that limiting trade of live chickens or increasing infection control practices during contagious periods may be an important step in reducing the spread of H5N1 and other emerging avian influenza viruses.
基金This study was supported by the National Mega-projects for Infectious Diseases(2017ZX10303401-004)。
文摘Bird infections with highly pathogenic avian influenza A(H5N6) viruses have been identified since 2014. With very limited occasion, the virus could sporadically spilled over to infect humans. It has been recognized that all human infections were within southern region of China's Mainland until the case reported here in Beijing in Aug. 2019. This was the first human case infected with highly pathogenic avian influenza A(H5N6) virus in northern China. The infection was confirmed by real-time RT-PCR assay. The whole genome sequences were obtained from clinical sample. Genetic characteristics of the virus were identified similar to those of previous avian influenza A(H5N6) viruses, retaining the main features of the avian influenza virus.
文摘As part of the USA’s National Strategy for Pandemic Influenza,an Interagency Strategic Plan for the Early Detection of Highly Pathogenic H5N1 Avian Influenza in Wild Migratory Birds was developed and implemented.From1April2006 through 31 March 2009,261946 samples fromwild birds and 101457 wild bird fecalsamples were collected in the USA;no highly pathogenic avian influenza was detected.The United States Department of Agriculture,and state and tribal cooperators accounted for 213115(81%)of the wild bird samples collected;31,27,21 and 21%of the samples were collected from theAtlantic,Pacific,Central and Mississippi flyways,respectively.More than 250 species of wild birds in all 50 states were sampled.The majority of wild birds(86%)were dabbling ducks,geese,swans and shorebirds.The apparent prevalence of low pathogenic avian influenza viruses during biological years 2007 and 2008 was 9.7 and 11.0%,respectively.The apparent prevalence of H5 and H7 subtypes across all species sampled were 0.5 and 0.06%,respectively.The pooled fecal samples(n=101539)positive for low pathogenic avian influenza were 4.0,6.7 and 4.7%for biological years 2006,2007 and 2008,respectively.The highly pathogenic early detection system for wild birds developed and implemented in the USA represents the largest coordinated wildlife disease surveillance system ever conducted.This effort provided evidence that wild birds in the USA were free of highly pathogenic avian influenza virus(given the expected minimum prevalence of 0.001%)at the 99.9%confidence level during the surveillance period.
基金supported by the National Basic Research Program(2011CB504702)the National Science Fund for Distinguished Young Scholars(31025029).
文摘Vaccination for highly pathogenic avian influenza(HPAI)has been implemented in China for a decade,however,the virus is still present in poultry.A series of recombinant vaccines,Re-1 to Re-7,have been developed and used,and Re-8 will also be used in clinical settings to prevent the prevailing flu strains.The question remains,when can China eradicate the disease?Here,we review the epidemiology of H5 HPAI along with the development,usage and problems of vaccines.Further suggestions for controlling the disease in China are provided.
基金supported by the Agricultural Science and Technology Innovation Program,Chinese Academy of Agricultural Sciences (ASTIP-IAED-2016)the Modern Agro-industry Technology Research System,China (CARS42-G24)
文摘Highly pathogenic avian influenza (HPAI) contamination via wild birds and rodents poses a threat to food security and safety. As chicken meat comprises an increasing proportion of diet in China, it is useful to determine whether broiler farmers are adopting wild bird and rodent controls to minimize the risk of HPAI impacts on food supply. Our study surveyed a cross sectional sample of 331 Chinese broiler farmers in six provinces. We find that only 47% of farmers (mainly farmers with large herds) adopted control measures against wild birds and rodents, while 14% adopted no measures. Farm size was the biggest driver of adoption followed by proportion of farm revenue derived from broiler production. However, southern farmers were at a far greater probability of non-adoption. We suggest that assistance in the form of education/training programs and subsidized traps or baiting controls across smaller producers could help raise of the adoption level toward more effective HPAI control.
基金This workwas supported by two grants, No. CHB1-31056-BE-11 from the US Civilian Research & Development Foundation from the National Institute of Allergy and Infectious Diseases and No. 31070785 from the National Natural Science Foundation of China. We thank Dr Jianmin Zhang and Dr Austin Cape for critical reading of the manuscript.
文摘Highly pathogenic avian influenza H5N 1 epidemics are a significant public health hazard. Genetically engineered H5N 1 viruses with mammalian transmission activity highlight the potential risk of a human influenza H5N 1 pandemic. Understanding the underlying principles of the innate immune system in response to influenza H5N 1 viruses will lead to improved prevention and control of these potentially deadly viruses, γδT cells act as the first line of defense against microbial infection and help initiate adaptive immune responses during the early stages of viral infection. In this study, we investigated the molecular mechanisms of γδ T cells in response to influenza H5N1 viral infection, We found that recombinant hemagglutinin (rHA) derived from three different strains of influenza H5N 1 viruses elicited the activation of γδ T cells cultured in peripheral blood mononuclear cells (PBMCs). Both the cell surface expression of CD69, an early activation marker on γδ T cells, and the production of interferon-y (IFN-y) were significantly increased. Notably, the rHA protein-induced γδ T-cell activation was not mediated by TCRγδ, NKG2D or pattern recognition receptors (PRRs) or NKp46 receptors. The interaction of rHA proteins with sialic acid receptors may play a critical role in γδ T-cell activation. Our data may provide insight into the mechanisms underlyingγδT-cell activation in response to infection with H5N1 viruses.