NKG2A is a NK cell exhaustion checkpoint for HCV persistence

Chao Zhang, Xiao-mei Wang, Shu-ran Li, Trix Twelkmeyer, Wei-hong Wang, Sheng-yuan Zhang, Shu-feng Wang, Ji-zheng Chen, Xia Jin, Yu-zhang Wu, Xin-wen Chen, Sheng-dian Wang, Jun-qi Niu, Hai-rong Chen () and Hong Tang ()
Additional contact information
Chao Zhang: Chinese Academy of Sciences
Xiao-mei Wang: The First Hospital of Jilin University
Shu-ran Li: Chinese Academy of Sciences
Trix Twelkmeyer: Chinese Academy of Sciences
Wei-hong Wang: Chinese Academy of Sciences
Sheng-yuan Zhang: Chinese Academy of Sciences
Shu-feng Wang: The Third Military Medical University
Ji-zheng Chen: Chinese Academy of Sciences
Xia Jin: Chinese Academy of Sciences
Yu-zhang Wu: The Third Military Medical University
Xin-wen Chen: Chinese Academy of Sciences
Sheng-dian Wang: Chinese Academy of Sciences
Jun-qi Niu: The First Hospital of Jilin University
Hai-rong Chen: Chinese Academy of Sciences
Hong Tang: Chinese Academy of Sciences

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: Abstract 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/OTg 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-γ 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.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-09212-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09212-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-09212-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().