DNA tumor virus oncogenes antagonize the cGAS-STING DNA sensing pathway

Menée sur des lignées cellulaires, cette étude met en évidence des mécanismes par lesquels, en inhibant la voie de signalisation cGAS-STING, des oncogènes de virus tumoraux à ADN favorisent l'échappement au système immunitaire

Résumé en anglais

Cyclic GMP-AMP synthase (cGAS) detects intracellular DNA and signals through the adapter protein STING to initiate the antiviral response to DNA viruses. Whether DNA viruses can prevent activation of the cGAS-STING pathway remains largely unknown. Here, we identify the viral oncogenes of the DNA tumor viruses, including E7 from human papillomavirus (HPV) and E1A from adenovirus, as potent and specific inhibitors of the cGAS-STING pathway. We show that the LXCXE motif of these oncoproteins, which is essential for blockade of the Retinoblastoma tumor suppressor, is also important for antagonizing DNA sensing. E1A and E7 bind to STING, and silencing of these oncogenes in human tumor cells restores the cGAS-STING pathway. Our findings reveal a host-virus conflict that may have shaped the evolution of viral oncogenes.