Host cell Z-RNAs activate ZBP1 during virus infections.

ABSTRACT: Herpes simplex virus 1 (HSV-1) and influenza A viruses (IAV) induce Z-form-nucleic-acid-binding protein 1 (ZBP1)-initiated cell death^1-8. ZBP1 is activated by Z-RNA^1,7,9, and the Z-RNAs that trigger ZBP1 during HSV-1 and IAV infections were assumed to be of viral origin¹. Here, however, we show that host cell-encoded Z-RNAs are major and sufficient ZBP1-activating ligands after infection by these two human pathogens. The majority of cellular Z-RNAs mapped to intergenic endogenous retroelements embedded within abnormally long 3' extensions of host cell mRNAs. These aberrant host cell transcripts arose as a consequence of disruption of transcription termination (DoTT)-a virus-driven phenomenon that disables cleavage and polyadenylation specificity factor (CPS

SUBMITTER: Yin C 

PROVIDER: S-EPMC12711578 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature