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

• DOI: 10.1007/s00018-025-05580-5
• Publication Date: 2025-01-21T04:03:10Z
• Authors: Andrés Louloudes-...; Pablo Nogales-Alt...; José M. Rojas; Jeury Veloz; Ana B. Carlón; Piet A. Van Rijn; Verónica Martín; Ana Fernández-Sesma; Noemí Sevilla
• Keywords: RNA Silencing; DNA virus; Transcription; RNA virus

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 can limit the replication of some RNA viruses. Some viruses have nonetheless evolved mechanisms antagonize cGAS sensing. In this study, we evaluated interaction between Bluetongue virus (BTV), prototypical dsRNA Orbivirus genus Sedoreoviridae family, cGAS. We found mitochondrial damage accumulation cytoplasm infected cells. addition, show BTV infection blocks DNA-induced prevents by inducing STING degradation. identify BTV-NS3 as viral protein responsible for degradation, showing NS3 physically interacts with its degradation through an autophagy-dependent mechanism. Taken together, these findings first time mechanism which interferes pathway evade innate immune response.