The human influenza A (H3N2) virus dominated the 2014-2015 winter season in many countries and caused massive morbid- ity and mortality because of its antigenic variation. So far, very little is known about the anti...The human influenza A (H3N2) virus dominated the 2014-2015 winter season in many countries and caused massive morbid- ity and mortality because of its antigenic variation. So far, very little is known about the antigenic patterns of the recent H3N2 virus. By systematically mapping the antigenic relationships of H3N2 strains isolated since 2010, we discovered that two groups with obvious antigenic divergence, named SW13 (A/Switzerland/9715293/2013-1ike strains) and HK14 (A/Hong Kong/5738/2014-1ike strains), co-circulated during the 2014-2015 winter season. HK14 group co-circulated with SW13 in Europe and the United States during this season, while there were few strains of HK14 in China's Mainland, where SW13 has dominated since 2012. Furthermore, we found that substitutions near the receptor-binding site on hemagglutinin played an im- portant role in the antigenic variation of both the groups. These findings provide a comprehensive understanding of the recent antigenic evolution of H3N2 virus and will aid in the selection of vaccine strains.展开更多
Influenza virus can rapidly change its antigenicity, via mutation in the hemagglutinin(HA) protein, to evade host immunity. The emergence of the novel human-infecting avian H7N9 virus in China has caused widespread co...Influenza virus can rapidly change its antigenicity, via mutation in the hemagglutinin(HA) protein, to evade host immunity. The emergence of the novel human-infecting avian H7N9 virus in China has caused widespread concern. However, evolution of the antigenicity of this virus is not well understood. Here, we inferred the antigenic epitopes of the HA protein from all H7 viruses, based on the five well-characterized HA epitopes of the human H3N2 virus. By comparing the two major H7 phylogenetic lineages, i.e., the Eurasian lineage and the North American lineage, we found that epitopes A and B are more frequently mutated in the Eurasian lineage, while epitopes B and C are more frequently mutated in the North American lineage. Furthermore, we found that the novel H7N9 virus(derived from the Eurasian lineage) isolated in China in the year 2013, contains six frequently mutated sites on epitopes that include site 135, which is located in the receptor binding domain. This indicates that the novel H7N9 virus that infects human may already have been subjected to gradual immune pressure and receptor-binding variation. Our results not only provide insights into the antigenic evolution of the H7 virus but may also help in the selection of suitable vaccine strains.展开更多
The virulence of influenza viruses is a complex multigenic trait.Previous studies about the virulence determinants of influenza viruses mainly focused on amino acid sites,ignoring the influence of nucleotide mutations...The virulence of influenza viruses is a complex multigenic trait.Previous studies about the virulence determinants of influenza viruses mainly focused on amino acid sites,ignoring the influence of nucleotide mutations.In this study,we collected>200 viral strains from 21 subtypes of influenza A viruses with virulence in mammals and obtained over 100 mammalian virulence-related nucleotide sites across the genome by computational analysis.Fifty of these nucleotide sites only experienced synonymous mutations.Experiments showed that synonymous mutations in three high-scoring nucleotide sites,i.e.,PB1–2031,PB1–633,and PB1–720,enhanced the pathogenicity of the influenza A(H1N1)viruses in mice.Besides,machine-learning models with accepted accuracy for predicting mammalian virulence of influenza A viruses were built.Overall,this study highlighted the importance of nucleotide mutations,especially synonymous mutations in viral virulence,and provided rapid methods for evaluating the virulence of influenza A viruses.It could be helpful for early warning of newly emerging influenza A viruses.展开更多
基金supported by the National Basic Research Program of China(2015CB910501)the Major National Earmark Project for Infectious Diseases(2014ZX10004002-001)+1 种基金the Key Research Program of the Chinese Academy of Sciences(KJZD-EW-L09-1-2)to Jiang Tai Jiaothe National Natural Science Foundation of China(31470273)to Wu Ai Ping
文摘The human influenza A (H3N2) virus dominated the 2014-2015 winter season in many countries and caused massive morbid- ity and mortality because of its antigenic variation. So far, very little is known about the antigenic patterns of the recent H3N2 virus. By systematically mapping the antigenic relationships of H3N2 strains isolated since 2010, we discovered that two groups with obvious antigenic divergence, named SW13 (A/Switzerland/9715293/2013-1ike strains) and HK14 (A/Hong Kong/5738/2014-1ike strains), co-circulated during the 2014-2015 winter season. HK14 group co-circulated with SW13 in Europe and the United States during this season, while there were few strains of HK14 in China's Mainland, where SW13 has dominated since 2012. Furthermore, we found that substitutions near the receptor-binding site on hemagglutinin played an im- portant role in the antigenic variation of both the groups. These findings provide a comprehensive understanding of the recent antigenic evolution of H3N2 virus and will aid in the selection of vaccine strains.
基金supported by the National Basic Research Program of China(2015CB910501)the Major National Earmark Project for Infectious Diseases(2014ZX10004002-001)+1 种基金the Key Research Program of the Chinese Academy of Sciences(KJZD-EW-L09-1-2)to Jiang Tai Jiaothe National Natural Science Foundation of China(31470273)to Wu Ai Ping
文摘Influenza virus can rapidly change its antigenicity, via mutation in the hemagglutinin(HA) protein, to evade host immunity. The emergence of the novel human-infecting avian H7N9 virus in China has caused widespread concern. However, evolution of the antigenicity of this virus is not well understood. Here, we inferred the antigenic epitopes of the HA protein from all H7 viruses, based on the five well-characterized HA epitopes of the human H3N2 virus. By comparing the two major H7 phylogenetic lineages, i.e., the Eurasian lineage and the North American lineage, we found that epitopes A and B are more frequently mutated in the Eurasian lineage, while epitopes B and C are more frequently mutated in the North American lineage. Furthermore, we found that the novel H7N9 virus(derived from the Eurasian lineage) isolated in China in the year 2013, contains six frequently mutated sites on epitopes that include site 135, which is located in the receptor binding domain. This indicates that the novel H7N9 virus that infects human may already have been subjected to gradual immune pressure and receptor-binding variation. Our results not only provide insights into the antigenic evolution of the H7 virus but may also help in the selection of suitable vaccine strains.
基金This work was supported by the National Key Plan for Scientific Research and Development of China(2016YFC1200200 and 2016YFD0500300)the National Natural Science Foundation of China(31671371)+1 种基金the Chinese Academy of Medical Sciences(2016-I2M-1-005)the Fundamental Research Funds for the Central Universities of China.
文摘The virulence of influenza viruses is a complex multigenic trait.Previous studies about the virulence determinants of influenza viruses mainly focused on amino acid sites,ignoring the influence of nucleotide mutations.In this study,we collected>200 viral strains from 21 subtypes of influenza A viruses with virulence in mammals and obtained over 100 mammalian virulence-related nucleotide sites across the genome by computational analysis.Fifty of these nucleotide sites only experienced synonymous mutations.Experiments showed that synonymous mutations in three high-scoring nucleotide sites,i.e.,PB1–2031,PB1–633,and PB1–720,enhanced the pathogenicity of the influenza A(H1N1)viruses in mice.Besides,machine-learning models with accepted accuracy for predicting mammalian virulence of influenza A viruses were built.Overall,this study highlighted the importance of nucleotide mutations,especially synonymous mutations in viral virulence,and provided rapid methods for evaluating the virulence of influenza A viruses.It could be helpful for early warning of newly emerging influenza A viruses.