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
季节性流感病毒仍对全球公共卫生安全构成巨大威胁,对老人、儿童以及免疫功能低下人群的危害尤其严重。疫苗接种是目前应对季节性流感疫情重要手段,然而由于抗原转换和抗原漂移,常出现疫苗株与实际病毒流行株的不匹配现象,因此迫切需要...季节性流感病毒仍对全球公共卫生安全构成巨大威胁,对老人、儿童以及免疫功能低下人群的危害尤其严重。疫苗接种是目前应对季节性流感疫情重要手段,然而由于抗原转换和抗原漂移,常出现疫苗株与实际病毒流行株的不匹配现象,因此迫切需要开发一种安全高效的广谱流感疫苗来对抗季节性流感病毒和潜在的流感大流行。抗原设计是研发新型疫苗的关键前提,我们利用马赛克(mosaic)遗传算法设计研发了一种具有广谱抗原表位覆盖率的靶向流感病毒神经氨酸酶(Neuraminidase,NA)的新型抗原(Mosaic-NA)。该抗原在最大程度上涵盖了所有已报道甲型流感病毒的NA1蛋白与NA2蛋白序列中的细胞毒性T淋巴细胞(Cytotoxic T lymphocyte,CTL)抗原表位,并保留了天然蛋白空间构象。因此,这种新型抗原预期可有效诱导出靶向保守表位的CTL反应和抗体反应,从而为研发通用流感疫苗提供新思路和理论基础。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.
文摘季节性流感病毒仍对全球公共卫生安全构成巨大威胁,对老人、儿童以及免疫功能低下人群的危害尤其严重。疫苗接种是目前应对季节性流感疫情重要手段,然而由于抗原转换和抗原漂移,常出现疫苗株与实际病毒流行株的不匹配现象,因此迫切需要开发一种安全高效的广谱流感疫苗来对抗季节性流感病毒和潜在的流感大流行。抗原设计是研发新型疫苗的关键前提,我们利用马赛克(mosaic)遗传算法设计研发了一种具有广谱抗原表位覆盖率的靶向流感病毒神经氨酸酶(Neuraminidase,NA)的新型抗原(Mosaic-NA)。该抗原在最大程度上涵盖了所有已报道甲型流感病毒的NA1蛋白与NA2蛋白序列中的细胞毒性T淋巴细胞(Cytotoxic T lymphocyte,CTL)抗原表位,并保留了天然蛋白空间构象。因此,这种新型抗原预期可有效诱导出靶向保守表位的CTL反应和抗体反应,从而为研发通用流感疫苗提供新思路和理论基础。
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.
