Splicing Suppression Alters STING Transcription Start Site to Attenuate Antiviral Innate Immunity [DCV FHV vs mi]

Recent studies have shown that invertebrates possess a related cGLR (cGAS-like receptor)-STING pathway. However, due to the lack of direct evidence demonstrating viral evasion of cGLR-STING-mediated immunity, the functional importance of cGLR-STING pathway in antiviral responses remains uncertain in invertebrates.

Here, we show that an insect picorna-like virus CrPV (Cricket Paralysis virus) inhibits STING-mediated antiviral activity by altering the transcription start site of STING. Mechanistically, CrPV infection down-regulates several spliceosomal genes and disrupts pre-mRNA splicing. This splicing impairment is sufficient to stall RNA polymerase II in transcriptional initiation condensates, reduce global transcription efficiency, and reprogram the transcription start site of STING.