Double-stranded RNA orbivirus disrupts the DNA-sensing cGAS-sting axis to prevent type I IFN induction.

ABSTRACT: Cyclic GMP-AMP synthase (cGAS) is a DNA sensing cellular receptor that induces IFN-I transcription in response to pathogen and host derived cytosolic DNA and can limit the replication of some RNA viruses. Some viruses have nonetheless evolved mechanisms to antagonize cGAS sensing. In this study, we evaluated the interaction between Bluetongue virus (BTV), the prototypical dsRNA virus of the Orbivirus genus and the Sedoreoviridae family, and cGAS. We found mitochondrial damage and DNA accumulation in the cytoplasm of infected cells. In addition, we show that BTV infection blocks DNA-induced IFN-I transcription and that virus infection prevents DNA sensing by inducing cGAS and STING degradation. We identify BTV-NS3 as the viral protein responsible for cGAS degradation, showing that NS3 physi

SUBMITTER: Louloudes-Lazaro A 

PROVIDER: S-EPMC11751250 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature