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

DNA tumor virus oncogenes antagonize the cGAS-STING DNA-sensing pathway.
Published: 
Oct 2015
Publisher: 
Science. 2015 Oct 30;350(6260):568-71. doi: 10.1126/science.aab3291. Epub 2015 Sep 24.
Author: 
Daniel B. Stetson, Ph.D.

Lau L1, Gray EE1, Brunette RL1, Stetson DB2.

Abstract

Cyclic 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.

Copyright © 2015, American Association for the Advancement of Science.

PMID:26405230