Cytotoxic lymphocytes counteract viral type I interferon immune evasion.

ABSTRACT: Viruses are recognized by host cell innate immunity through viral RNA/DNA sensing by cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING). However, many viruses evade cGAS-STING signaling and antiviral IFN-β response. Here, we show that natural killer (NK) cells counteract immune evasion of type I interferon response upon human cytomegalovirus (HCMV) infection. NK cells enhance IFN-β response in virus-infected cells more efficiently than perforin-knockout and GrM-knockout NK cells. Mechanistically, GrM cleaves viral pp71 into two fragments, the first, like full-length pp71, still inhibits cGAS-STING-IFN-β response but is rapidly degraded by the proteasome, and the second fragment that rather augments IFN-β and outperforms full-length pp71 inhibition of STING. NK cells cann

SUBMITTER: Schakelaar MY 

PROVIDER: S-EPMC12912695 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature