Nkg2a is a nk cell exhaustion checkpoint for hcv persistence
文献类型:期刊论文
作者 | Zhang, Chao1,2,3; Wang, Xiao-mei4; Li, Shu-ran1,2,3,5; Twelkmeyer, Trix1,2,6; Wang, Wei-hong1,2,3,5; Zhang, Sheng-Yuan1,2,3,7; Wang, Shu-feng8; Chen, Ji-zheng9,10; Jin, Xia6; Wu, Yu-zhang8 |
刊名 | Nature communications |
出版日期 | 2019-04-03 |
卷号 | 10页码:11 |
ISSN号 | 2041-1723 |
DOI | 10.1038/s41467-019-09212-y |
通讯作者 | Chen, hai-rong(hairong.chen@ibp.ac.cn) ; Tang, hong(htang@ips.ac.cn) |
英文摘要 | Exhaustion of cytotoxic effector natural killer (nk) and cd8(+) t cells have important functions in the establishment of persistent viral infections, but how exhaustion is induced during chronic hepatitis c virus (hcv) infection remains poorly defined. here we show, using the humanized c/o-tg mice permissive for persistent hcv infection, that nk and cd8(+) t cells become sequentially exhausted shortly after their transient hepatic infiltration and activation in acute hcv infection. hcv infection upregulates qa-1 expression in hepatocytes, which ligates nkg2a to induce nk cell exhaustion. antibodies targeting nkg2a or qa-1 prevents nk exhaustion and promotes nk-dependent hcv clearance. moreover, reactivated nk cells provide sufficient ifn-gamma that helps rejuvenate polyclonal hcv cd8(+) t cell response and clearance of hcv. our data thus show that nkg2a serves as a critical checkpoint for hcv-induced nk exhaustion, and that nkg2a blockade sequentially boosts interdependent nk and cd8(+) t cell functions to prevent persistent hcv infection. |
WOS关键词 | HEPATITIS-C VIRUS ; NATURAL-KILLER-CELLS ; T-CELLS ; UP-REGULATION ; IN-VITRO ; INFECTION ; RESPONSES ; ACTIVATION ; BLOCKADE ; EXPRESSION |
WOS研究方向 | Science & Technology - Other Topics |
WOS类目 | Multidisciplinary Sciences |
语种 | 英语 |
出版者 | NATURE PUBLISHING GROUP |
WOS记录号 | WOS:000463170600006 |
URI标识 | http://www.irgrid.ac.cn/handle/1471x/2373162 |
专题 | 武汉病毒研究所 |
通讯作者 | Chen, Hai-rong; Tang, Hong |
作者单位 | 1.Chinese Acad Sci, Joint Lab Infect & Immun, Inst Pasteur Shanghai, Beijing 100101, Peoples R China 2.Chinese Acad Sci, Inst Biophys, Beijing 100101, Peoples R China 3.Chinese Acad Sci, Inst Biophys, Key Lab Infect & Immun, Beijing 100101, Peoples R China 4.Jilin Univ, Dept Hepatol, Hosp 1, Changchun 130021, Jilin, Peoples R China 5.Univ Chinese Acad Sci, Coll Life Sci, Beijing 100049, Peoples R China 6.Chinese Acad Sci, Inst Pasteur Shanghai, Key Lab Mol Virol & Immunol, Shanghai 200031, Peoples R China 7.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China 8.Third Mil Med Univ, Inst Immunol, Chongqing 400038, Peoples R China 9.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430071, Hubei, Peoples R China 10.Chinese Acad Sci, Wuhan Inst Virol, Ctr Viral Pathol, Wuhan 430071, Hubei, Peoples R China |
推荐引用方式 GB/T 7714 | Zhang, Chao,Wang, Xiao-mei,Li, Shu-ran,et al. Nkg2a is a nk cell exhaustion checkpoint for hcv persistence[J]. Nature communications,2019,10:11. |
APA | Zhang, Chao.,Wang, Xiao-mei.,Li, Shu-ran.,Twelkmeyer, Trix.,Wang, Wei-hong.,...&Tang, Hong.(2019).Nkg2a is a nk cell exhaustion checkpoint for hcv persistence.Nature communications,10,11. |
MLA | Zhang, Chao,et al."Nkg2a is a nk cell exhaustion checkpoint for hcv persistence".Nature communications 10(2019):11. |
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来源:武汉病毒研究所
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