Heterosubtypic Protections against Human-Infecting Avian Influenza Viruses Correlate to Biased Cross-T-Cell Responses
ABSTRACT Against a backdrop of seasonal influenza virus epidemics, emerging avian influenza viruses (AIVs) occasionally jump from birds to humans, posing a public health risk, especially with the recent sharp increase in H7N9 infections. Evaluations of cross-reactive T-cell immunity to seasonal infl...
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American Society for Microbiology
2018
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oai:doaj.org-article:22ce28a943a94f0e8226fb71963508492021-11-15T16:00:15ZHeterosubtypic Protections against Human-Infecting Avian Influenza Viruses Correlate to Biased Cross-T-Cell Responses10.1128/mBio.01408-182150-7511https://doaj.org/article/22ce28a943a94f0e8226fb71963508492018-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01408-18https://doaj.org/toc/2150-7511ABSTRACT Against a backdrop of seasonal influenza virus epidemics, emerging avian influenza viruses (AIVs) occasionally jump from birds to humans, posing a public health risk, especially with the recent sharp increase in H7N9 infections. Evaluations of cross-reactive T-cell immunity to seasonal influenza viruses and human-infecting AIVs have been reported previously. However, the roles of influenza A virus-derived epitopes in the cross-reactive T-cell responses and heterosubtypic protections are not well understood; understanding those roles is important for preventing and controlling new emerging AIVs. Here, among the members of a healthy population presumed to have previously been infected by pandemic H1N1 (pH1N1), we found that pH1N1-specific T cells showed cross- but biased reactivity to human-infecting AIVs, i.e., H5N1, H6N1, H7N9, and H9N2, which correlates with distinct protections. Through a T-cell epitope-based phylogenetic analysis, the cellular immunogenic clustering expanded the relevant conclusions to a broader range of virus strains. We defined the potential key conserved epitopes required for cross-protection and revealed the molecular basis for the immunogenic variations. Our study elucidated an overall profile of cross-reactivity to AIVs and provided useful recommendations for broad-spectrum vaccine development. IMPORTANCE We revealed preexisting but biased T-cell reactivity of pH1N1 influenza virus to human-infecting AIVs, which provided distinct protections. The cross-reactive T-cell recognition had a regular pattern that depended on the T-cell epitope matrix revealed via bioinformatics analysis. Our study elucidated an overall profile of cross-reactivity to AIVs and provided useful recommendations for broad-spectrum vaccine development.Min ZhaoKefang LiuJiejian LuoShuguang TanChuansong QuanShuijun ZhangYan ChaiJianxun QiYan LiYuhai BiHaixia XiaoGary WongJianfang ZhouTaijiao JiangWenjun LiuHongjie YuJinghua YanYingxia LiuYuelong ShuGuizhen WuAiping WuGeorge F. GaoWilliam J. LiuAmerican Society for MicrobiologyarticleT-cell responsesavian influenza virusescross-reactivityheterosubtypic protectionMicrobiologyQR1-502ENmBio, Vol 9, Iss 4 (2018) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
T-cell responses avian influenza viruses cross-reactivity heterosubtypic protection Microbiology QR1-502 |
| spellingShingle |
T-cell responses avian influenza viruses cross-reactivity heterosubtypic protection Microbiology QR1-502 Min Zhao Kefang Liu Jiejian Luo Shuguang Tan Chuansong Quan Shuijun Zhang Yan Chai Jianxun Qi Yan Li Yuhai Bi Haixia Xiao Gary Wong Jianfang Zhou Taijiao Jiang Wenjun Liu Hongjie Yu Jinghua Yan Yingxia Liu Yuelong Shu Guizhen Wu Aiping Wu George F. Gao William J. Liu Heterosubtypic Protections against Human-Infecting Avian Influenza Viruses Correlate to Biased Cross-T-Cell Responses |
| description |
ABSTRACT Against a backdrop of seasonal influenza virus epidemics, emerging avian influenza viruses (AIVs) occasionally jump from birds to humans, posing a public health risk, especially with the recent sharp increase in H7N9 infections. Evaluations of cross-reactive T-cell immunity to seasonal influenza viruses and human-infecting AIVs have been reported previously. However, the roles of influenza A virus-derived epitopes in the cross-reactive T-cell responses and heterosubtypic protections are not well understood; understanding those roles is important for preventing and controlling new emerging AIVs. Here, among the members of a healthy population presumed to have previously been infected by pandemic H1N1 (pH1N1), we found that pH1N1-specific T cells showed cross- but biased reactivity to human-infecting AIVs, i.e., H5N1, H6N1, H7N9, and H9N2, which correlates with distinct protections. Through a T-cell epitope-based phylogenetic analysis, the cellular immunogenic clustering expanded the relevant conclusions to a broader range of virus strains. We defined the potential key conserved epitopes required for cross-protection and revealed the molecular basis for the immunogenic variations. Our study elucidated an overall profile of cross-reactivity to AIVs and provided useful recommendations for broad-spectrum vaccine development. IMPORTANCE We revealed preexisting but biased T-cell reactivity of pH1N1 influenza virus to human-infecting AIVs, which provided distinct protections. The cross-reactive T-cell recognition had a regular pattern that depended on the T-cell epitope matrix revealed via bioinformatics analysis. Our study elucidated an overall profile of cross-reactivity to AIVs and provided useful recommendations for broad-spectrum vaccine development. |
| format |
article |
| author |
Min Zhao Kefang Liu Jiejian Luo Shuguang Tan Chuansong Quan Shuijun Zhang Yan Chai Jianxun Qi Yan Li Yuhai Bi Haixia Xiao Gary Wong Jianfang Zhou Taijiao Jiang Wenjun Liu Hongjie Yu Jinghua Yan Yingxia Liu Yuelong Shu Guizhen Wu Aiping Wu George F. Gao William J. Liu |
| author_facet |
Min Zhao Kefang Liu Jiejian Luo Shuguang Tan Chuansong Quan Shuijun Zhang Yan Chai Jianxun Qi Yan Li Yuhai Bi Haixia Xiao Gary Wong Jianfang Zhou Taijiao Jiang Wenjun Liu Hongjie Yu Jinghua Yan Yingxia Liu Yuelong Shu Guizhen Wu Aiping Wu George F. Gao William J. Liu |
| author_sort |
Min Zhao |
| title |
Heterosubtypic Protections against Human-Infecting Avian Influenza Viruses Correlate to Biased Cross-T-Cell Responses |
| title_short |
Heterosubtypic Protections against Human-Infecting Avian Influenza Viruses Correlate to Biased Cross-T-Cell Responses |
| title_full |
Heterosubtypic Protections against Human-Infecting Avian Influenza Viruses Correlate to Biased Cross-T-Cell Responses |
| title_fullStr |
Heterosubtypic Protections against Human-Infecting Avian Influenza Viruses Correlate to Biased Cross-T-Cell Responses |
| title_full_unstemmed |
Heterosubtypic Protections against Human-Infecting Avian Influenza Viruses Correlate to Biased Cross-T-Cell Responses |
| title_sort |
heterosubtypic protections against human-infecting avian influenza viruses correlate to biased cross-t-cell responses |
| publisher |
American Society for Microbiology |
| publishDate |
2018 |
| url |
https://doaj.org/article/22ce28a943a94f0e8226fb7196350849 |
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