DNA tumor virus oncogenes antagonize the cGAS-STING DNA-sensing pathway
2015; American Association for the Advancement of Science; Volume: 350; Issue: 6260 Linguagem: Inglês
10.1126/science.aab3291
ISSN1095-9203
AutoresLaura Lau, Elizabeth Gray, Rebecca Brunette, Daniel B. Stetson,
Tópico(s)Herpesvirus Infections and Treatments
ResumoCyclic guanosine monophosphate-adenosine monophosphate 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 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.
Referência(s)