NKG2A is a NK cell exhaustion checkpoint for HCV persistence
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; Chen, Xin-wen9,10; Wang, Sheng-dian3; Niu, Jun-qi4; Chen, Hai-rong1,2,3; Tang, Hong1,2,6,9,10
2019-04-03
Source PublicationNATURE COMMUNICATIONS
ISSN2041-1723
Volume10
Status已发表
DOI10.1038/s41467-019-09212-y
AbstractExhaustion 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.
Indexed BySCI
Language英语
Funding ProjectCAS[QYZDJ-SSW-SMC026] ; CAS[153831KYSB20160038] ; CAS[XDB2903000]
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000463170600006
PublisherNATURE PUBLISHING GROUP
WOS KeywordHEPATITIS-C VIRUS ; NATURAL-KILLER-CELLS ; T-CELLS ; UP-REGULATION ; IN-VITRO ; INFECTION ; RESPONSES ; ACTIVATION ; BLOCKADE ; EXPRESSION
Original Document TypeArticle
Citation statistics
Cited Times:9[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://kms.shanghaitech.edu.cn/handle/2MSLDSTB/34189
Collection生命科学与技术学院_硕士生
Corresponding AuthorChen, Hai-rong; Tang, Hong
Affiliation1.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
Recommended Citation
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.
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.
MLA Zhang, Chao,et al."NKG2A is a NK cell exhaustion checkpoint for HCV persistence".NATURE COMMUNICATIONS 10(2019).
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