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
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
In this work, 25 3-O-β-chacotriosyl ursolic acid derivatives were employed to achieve the highly reliable and predictive 3 D-QSAR models by Co MFA and Co MSIA methods, respectively. The predictive capabilities of two...In this work, 25 3-O-β-chacotriosyl ursolic acid derivatives were employed to achieve the highly reliable and predictive 3 D-QSAR models by Co MFA and Co MSIA methods, respectively. The predictive capabilities of two constructed CoMFA and CoMSIA models were verified by the leave-one-out cross-validation method. The results showed that the cross-validated coefficient(q2) and non-cross-validated coefficient(R2) were 0.559, 0.981 in the CoMFA model and 0.696, 0.978 in the CoM SIA model, respectively, which suggests that these two models are robust and have good exterior predictive capabilities. Furthermore, based on the contour maps information of two models, ten novel inhibitors with higher inhibitory potency were designed, and the quantum chemical calculation of density functional theory(DFT) was performed to investigate the mechanism why the designed molecules have stronger inhibitory activity than the lead compound. The calculations show that the C-50 position of lead compound is a key active site for the enhancement of inhibitory activity, and it should be introduced into the large electron withdrawing group, which would result in generating potent and selective H5 N1 entry inhibitors. We expect that the results in this paper could provide important information to develop new potent H5 N1 entry inhibitors.展开更多
Non-structural protein 1(NS1)is an important virulence factor of the highly pathogenic H5N1 avian influenza virus.A five-amino-acid(5 aa)deletion at position 80–84 and an aspartic acid to glutamic acid substitution a...Non-structural protein 1(NS1)is an important virulence factor of the highly pathogenic H5N1 avian influenza virus.A five-amino-acid(5 aa)deletion at position 80–84 and an aspartic acid to glutamic acid substitution at position 92(D92E)are two major NS1 mutations that are highly correlated with enhanced virulence.To investigate the effect of these mutations in H5N1 virulence,three H5N1-NS1 variants were constructed:NS51(lacking 5 aa at position 80–84),NS51(I)(carrying a 5-aa insertion at position 80–84)and NS51(IM)(carrying both the 5-aa insertion and the D92E mutation).We examined the effects of these mutations on interferon(IFN)induction,tumor-necrosis factor(TNF)a response,p53 activity and apoptosis.We found that the D92E mutation eliminated NS1’s repressive effect on IFN induction,while the 5-aa deletion resulted in enhanced resistance to TNFa responses.We also observed that all three variants exhibited a similar suppressive effect on p53 transcriptional activity,although none of them significantly influenced apoptosis of host cells.Our findings shed new light on the role of NS1 in the pathogenicity of H5N1 virus.展开更多
Interleukin-17(IL-17),a member of the IL-17 cytokine family,plays a crucial role in mediating the immune response against extracellular bacteria and fungi in the lung.Although there is increasing evidence that IL-17 i...Interleukin-17(IL-17),a member of the IL-17 cytokine family,plays a crucial role in mediating the immune response against extracellular bacteria and fungi in the lung.Although there is increasing evidence that IL-17 is involved in protective immunity against H1 and H3 influenza virus infections,little is known about the role of IL-17 in the highly pathogenic H5N1 influenza virus infection.In this study,we show that H5N1-infected IL-17 knockout(KO)mice exhibit markedly increased weight loss,more pronounced lung immunopathology and significantly reduced survival rates as compared with infected wild-type controls.Moreover,the frequency of B cells in the lung were substantially decreased in IL-17 KO mice after virus infection,which correlated with reduced CXCR5 expression in B cells and decreased CXCL13 production in the lung tissue of IL-17 KO mice.Consistent with this observation,B cells from IL-17 KO mice exhibited a significant reduction in chemokine-mediated migration in culture.Taken together,these findings demonstrate a critical role for IL-17 in mediating the recruitment of B cells to the site of pulmonary influenza virus infection in mice.展开更多
Background Southeast China is one of the sites of influenza origin. During 2003-2004, nine avian influenza outbreaks took place in Guangdong Province. But no human case was reported. To examine the status of potential...Background Southeast China is one of the sites of influenza origin. During 2003-2004, nine avian influenza outbreaks took place in Guangdong Province. But no human case was reported. To examine the status of potential human infection by human influenza (H1N1, H3N2) and avian influenza (H5N1, H7N7, H9N2) in the avian influenza epidemic area of Guangdong Province, China, we conducted a seroepidemiologic survey in the people of this area from April to June of 2004.Methods Three out of 9 H5N1 avian influenza affected poultry areas in Guangdong were randomly selected, and the population living within 3 kilometers of the affected poultries were chosen as the survey subjects. One thousand two hundred and fourteen people were selected from 3 villages at random. Human and avian influenza antibody titers were determined by hemagglutination-inhibition (HI) test and microneutralization test (MNT). Results The positive rate of antibody to H5N1 was 3.03% in the occupational exposure group and 2.34% in general citizens group; that of H9N2 was 9.52% in the occupational exposure group and 3.76% in the general citizens group. Moreover one case in the occupational exposure group was positive for H7N7. One year later, all previously positive cases had become negative except for one H5N1-positive case. Conclusion The observations imply that H5N1 and H9N2 avian influenza silent infections exist in Guangdong populations.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
The continuing outbreaks of avian influenza A H5N1 virus infection in Asia and Africa have caused worldwide concern because of the high mortality rates in poultry,suggesting its potential to become a pandemic influenz...The continuing outbreaks of avian influenza A H5N1 virus infection in Asia and Africa have caused worldwide concern because of the high mortality rates in poultry,suggesting its potential to become a pandemic influenza virus in humans.The transmission route of the virus among either the same species or different species is not yet clear.Broilers and BABL/c mice were inoculated with the H5N1 strain of influenza A virus isolated from birds.The animals were inoculated with 0.1 mL 106.83 TCID50 of H5N1 virus oronasally,intraperitoneally and using eye drops.The viruses were examined by virological and pathological assays.In addition,to detect horizontal transmission,in each group,healthy chicks and mice were mixed with those infected.Viruses were detected in homogenates of the heart,liver,spleen,kidney and blood of the infected mice and chickens.Virus antigen was not detected in the spleen,kidney or gastrointestinal tract,but detected by Plaque Forming Unit(PFU)assay in the brain,liver and lung without degenerative change in these organs(in the group inoculated using eye drops.The detection results for mice inoculated using eye drops suggest that this virus might have a different tissue tropism from other influenza viruses mainly restricted to the respiratory tract in mice.All chicken samples tested positive for the virus,regardless of the method of inoculation.Avian influenza A H5N1 viruses are highly pathogenic to chickens,but its virulence in other animals is not yet known.To sum up,the results suggest that the virus replicates not only in different animal species but also through different routes of infection.In addition,the virus was detection not only in the respiratory tract but also in multiple extra-respiratory tissues.This study demonstrates that H5N1 virus infection in mice can cause systemic disease and spread through potentially novel routes within and between mammalian hosts.展开更多
With the support by the National Natural Science Foundation of China,the research team led by Prof.Yu Hongjie(余宏杰)at the School of Public Health,Fudan University,Key Laboratory of Public Health Safety,Ministry of E...With the support by the National Natural Science Foundation of China,the research team led by Prof.Yu Hongjie(余宏杰)at the School of Public Health,Fudan University,Key Laboratory of Public Health Safety,Ministry of Education,and the Key Laboratory of Surveillance and Early Warning on Infectious Disease,Chinese Center for Disease Control and Prevention,has published the paper entitled“Global epi-展开更多
In the present study,we used nucleotide and protein sequences of avian influenza virus H5N1,which were obtained in Asia and Africa,analyzed HA proteins using ClustalX1.83 and MEGA4.0,and built a genetic evolutionary t...In the present study,we used nucleotide and protein sequences of avian influenza virus H5N1,which were obtained in Asia and Africa,analyzed HA proteins using ClustalX1.83 and MEGA4.0,and built a genetic evolutionary tree of HA nucleotides.The analysis revealed that the receptor specificity amino acid of A/HK/213/2003,A/Turkey/65596/2006 and etc mutated into QNG,which could bind withá-2,3 galactose andá-2,6 galactose.A mutation might thus take place and lead to an outbreak of human infections of avian influenza virus.The mutations of HA protein amino acids from 2004 to 2009 coincided with human infections provided by the World Health Organization,indicating a“low–high–highest–high–low”pattern.We also found out that virus strains in Asia are from different origins:strains from Southeast Asia and East Asia are of the same origin,whereas those from West Asia,South Asia and Africa descend from one ancestor.The composition of the phylogenetic tree and mutations of key site amino acids in HA proteins reflected the fact that the majority of strains are regional and long term,and virus diffusions exist between China,Laos,Malaysia,Indonesia,Azerbaijan,Turkey and Iraq.We would advise that pertinent vaccines be developed and due attention be paid to the spread of viruses between neighboring countries and the dangers of virus mutation and evolution.展开更多
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.
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 Natural Science Foundation of Guangxi Province(Nos.2013GXNSFAA019019 and 2013GXNSFAA019041)
文摘In this work, 25 3-O-β-chacotriosyl ursolic acid derivatives were employed to achieve the highly reliable and predictive 3 D-QSAR models by Co MFA and Co MSIA methods, respectively. The predictive capabilities of two constructed CoMFA and CoMSIA models were verified by the leave-one-out cross-validation method. The results showed that the cross-validated coefficient(q2) and non-cross-validated coefficient(R2) were 0.559, 0.981 in the CoMFA model and 0.696, 0.978 in the CoM SIA model, respectively, which suggests that these two models are robust and have good exterior predictive capabilities. Furthermore, based on the contour maps information of two models, ten novel inhibitors with higher inhibitory potency were designed, and the quantum chemical calculation of density functional theory(DFT) was performed to investigate the mechanism why the designed molecules have stronger inhibitory activity than the lead compound. The calculations show that the C-50 position of lead compound is a key active site for the enhancement of inhibitory activity, and it should be introduced into the large electron withdrawing group, which would result in generating potent and selective H5 N1 entry inhibitors. We expect that the results in this paper could provide important information to develop new potent H5 N1 entry inhibitors.
基金We are grateful to Dr William Ba-Thein for helpful discussion and editing of the manuscript.We thank Dr Xu Liyan for the use of a TD20/20 luminometer.This work was supported by the National Natural Science Foundation of China(No.30771988and No.30972766)Specialized Research Fund for the Doctoral Program of Higher Education(No.20094402110004)+3 种基金Guangdong Natural Science Foundation(No.8151503102000022 and 9451503102003499)Outstanding Young Scientists Foundation of Guangdong Province Education Department(No.LYM08056)State Key Lab of Agriculture Microbiology Open Foundation(No.AML200910)Shantou University Medical College Research Foundation.
文摘Non-structural protein 1(NS1)is an important virulence factor of the highly pathogenic H5N1 avian influenza virus.A five-amino-acid(5 aa)deletion at position 80–84 and an aspartic acid to glutamic acid substitution at position 92(D92E)are two major NS1 mutations that are highly correlated with enhanced virulence.To investigate the effect of these mutations in H5N1 virulence,three H5N1-NS1 variants were constructed:NS51(lacking 5 aa at position 80–84),NS51(I)(carrying a 5-aa insertion at position 80–84)and NS51(IM)(carrying both the 5-aa insertion and the D92E mutation).We examined the effects of these mutations on interferon(IFN)induction,tumor-necrosis factor(TNF)a response,p53 activity and apoptosis.We found that the D92E mutation eliminated NS1’s repressive effect on IFN induction,while the 5-aa deletion resulted in enhanced resistance to TNFa responses.We also observed that all three variants exhibited a similar suppressive effect on p53 transcriptional activity,although none of them significantly influenced apoptosis of host cells.Our findings shed new light on the role of NS1 in the pathogenicity of H5N1 virus.
基金supported by the Research Fund for the Control of Infectious Diseases(RFCID),Food and Health Bureau,Hong Kong SAR Government(No.10091002).
文摘Interleukin-17(IL-17),a member of the IL-17 cytokine family,plays a crucial role in mediating the immune response against extracellular bacteria and fungi in the lung.Although there is increasing evidence that IL-17 is involved in protective immunity against H1 and H3 influenza virus infections,little is known about the role of IL-17 in the highly pathogenic H5N1 influenza virus infection.In this study,we show that H5N1-infected IL-17 knockout(KO)mice exhibit markedly increased weight loss,more pronounced lung immunopathology and significantly reduced survival rates as compared with infected wild-type controls.Moreover,the frequency of B cells in the lung were substantially decreased in IL-17 KO mice after virus infection,which correlated with reduced CXCR5 expression in B cells and decreased CXCL13 production in the lung tissue of IL-17 KO mice.Consistent with this observation,B cells from IL-17 KO mice exhibited a significant reduction in chemokine-mediated migration in culture.Taken together,these findings demonstrate a critical role for IL-17 in mediating the recruitment of B cells to the site of pulmonary influenza virus infection in mice.
文摘Background Southeast China is one of the sites of influenza origin. During 2003-2004, nine avian influenza outbreaks took place in Guangdong Province. But no human case was reported. To examine the status of potential human infection by human influenza (H1N1, H3N2) and avian influenza (H5N1, H7N7, H9N2) in the avian influenza epidemic area of Guangdong Province, China, we conducted a seroepidemiologic survey in the people of this area from April to June of 2004.Methods Three out of 9 H5N1 avian influenza affected poultry areas in Guangdong were randomly selected, and the population living within 3 kilometers of the affected poultries were chosen as the survey subjects. One thousand two hundred and fourteen people were selected from 3 villages at random. Human and avian influenza antibody titers were determined by hemagglutination-inhibition (HI) test and microneutralization test (MNT). Results The positive rate of antibody to H5N1 was 3.03% in the occupational exposure group and 2.34% in general citizens group; that of H9N2 was 9.52% in the occupational exposure group and 3.76% in the general citizens group. Moreover one case in the occupational exposure group was positive for H7N7. One year later, all previously positive cases had become negative except for one H5N1-positive case. Conclusion The observations imply that H5N1 and H9N2 avian influenza silent infections exist in Guangdong populations.
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.
基金supported by grants from The National Key Basic Research Chinese Academy of Sciences Knowledge Innovation Program of the major directions projects(KSCX2-YW-N-063)Development Program of China(9732007BC109103)+1 种基金the Chinese Academy of Sciences Knowledge Innovation Program of the major directions projects(KSCX2-YW-N-063)a NWRC USDA-IOZ CAS joint project(0760621234).
文摘The continuing outbreaks of avian influenza A H5N1 virus infection in Asia and Africa have caused worldwide concern because of the high mortality rates in poultry,suggesting its potential to become a pandemic influenza virus in humans.The transmission route of the virus among either the same species or different species is not yet clear.Broilers and BABL/c mice were inoculated with the H5N1 strain of influenza A virus isolated from birds.The animals were inoculated with 0.1 mL 106.83 TCID50 of H5N1 virus oronasally,intraperitoneally and using eye drops.The viruses were examined by virological and pathological assays.In addition,to detect horizontal transmission,in each group,healthy chicks and mice were mixed with those infected.Viruses were detected in homogenates of the heart,liver,spleen,kidney and blood of the infected mice and chickens.Virus antigen was not detected in the spleen,kidney or gastrointestinal tract,but detected by Plaque Forming Unit(PFU)assay in the brain,liver and lung without degenerative change in these organs(in the group inoculated using eye drops.The detection results for mice inoculated using eye drops suggest that this virus might have a different tissue tropism from other influenza viruses mainly restricted to the respiratory tract in mice.All chicken samples tested positive for the virus,regardless of the method of inoculation.Avian influenza A H5N1 viruses are highly pathogenic to chickens,but its virulence in other animals is not yet known.To sum up,the results suggest that the virus replicates not only in different animal species but also through different routes of infection.In addition,the virus was detection not only in the respiratory tract but also in multiple extra-respiratory tissues.This study demonstrates that H5N1 virus infection in mice can cause systemic disease and spread through potentially novel routes within and between mammalian hosts.
文摘With the support by the National Natural Science Foundation of China,the research team led by Prof.Yu Hongjie(余宏杰)at the School of Public Health,Fudan University,Key Laboratory of Public Health Safety,Ministry of Education,and the Key Laboratory of Surveillance and Early Warning on Infectious Disease,Chinese Center for Disease Control and Prevention,has published the paper entitled“Global epi-
基金supported by CAS Innovation Program(KSCX2-YW-N-063)China MOST(2006BAD06A01),IDRC,USDA and NIH.
文摘In the present study,we used nucleotide and protein sequences of avian influenza virus H5N1,which were obtained in Asia and Africa,analyzed HA proteins using ClustalX1.83 and MEGA4.0,and built a genetic evolutionary tree of HA nucleotides.The analysis revealed that the receptor specificity amino acid of A/HK/213/2003,A/Turkey/65596/2006 and etc mutated into QNG,which could bind withá-2,3 galactose andá-2,6 galactose.A mutation might thus take place and lead to an outbreak of human infections of avian influenza virus.The mutations of HA protein amino acids from 2004 to 2009 coincided with human infections provided by the World Health Organization,indicating a“low–high–highest–high–low”pattern.We also found out that virus strains in Asia are from different origins:strains from Southeast Asia and East Asia are of the same origin,whereas those from West Asia,South Asia and Africa descend from one ancestor.The composition of the phylogenetic tree and mutations of key site amino acids in HA proteins reflected the fact that the majority of strains are regional and long term,and virus diffusions exist between China,Laos,Malaysia,Indonesia,Azerbaijan,Turkey and Iraq.We would advise that pertinent vaccines be developed and due attention be paid to the spread of viruses between neighboring countries and the dangers of virus mutation and evolution.