| First Author | Zhang C | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 1507 |
| PubMed ID | 30944315 | Mgi Jnum | J:274931 |
| Mgi Id | MGI:6286991 | Doi | 10.1038/s41467-019-09212-y |
| Citation | Zhang C, et al. (2019) NKG2A is a NK cell exhaustion checkpoint for HCV persistence. Nat Commun 10(1):1507 |
| abstractText | 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. |
