Inhibition of cGAS DNA Sensing by a Herpesvirus Virion Protein

Wu JJ, Li W, Shao Y, Avey D, Fu B, Gillen J, Hand T, Ma S, Liu X, Miley W, Konrad A, Neipel F, Stürzl M, Whitby D, Li H, Zhu F (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Cell Host & Microbe Elsevier (Cell Press)

Book Volume: 18

Pages Range: 333-44

Journal Issue: 3

DOI: 10.1016/j.chom.2015.07.015

Abstract

Invading viral DNA can be recognized by the host cytosolic DNA sensor, cyclic GMP-AMP (cGAMP) synthase (cGAS), resulting in production of the second messenger cGAMP, which directs the adaptor protein STING to stimulate production of type I interferons (IFNs). Although several DNA viruses are sensed by cGAS, viral strategies targeting cGAS are virtually unknown. We report here that Kaposi's sarcoma-associated herpesvirus (KSHV) ORF52, an abundant gammaherpesvirus-specific tegument protein, subverts cytosolic DNA sensing by directly inhibiting cGAS enzymatic activity through a mechanism involving both cGAS binding and DNA binding. Moreover, ORF52 homologs in other gammaherpesviruses also inhibit cGAS activity and similarly bind cGAS and DNA, suggesting conserved inhibitory mechanisms. Furthermore, KSHV infection evokes cGAS-dependent responses that can limit the infection, and an ORF52 null mutant exhibits increased cGAS signaling. Our findings reveal a mechanism through which gammaherpesviruses antagonize host cGAS DNA sensing.

Authors with CRIS profile

Frank Neipel Institute of Clinical and Molecular Virology Michael Stürzl Professur für Molekulare und Experimentelle Chirurgie

Involved external institutions

Florida State University (FSU) US United States (USA) (US) The Frederick National Laboratory for Cancer Research US United States (USA) (US)

How to cite

APA:

Wu, J.-J., Li, W., Shao, Y., Avey, D., Fu, B., Gillen, J.,... Zhu, F. (2015). Inhibition of cGAS DNA Sensing by a Herpesvirus Virion Protein. Cell Host & Microbe, 18(3), 333-44. https://doi.org/10.1016/j.chom.2015.07.015

MLA:

Wu, Jian-Jun, et al. "Inhibition of cGAS DNA Sensing by a Herpesvirus Virion Protein." Cell Host & Microbe 18.3 (2015): 333-44.

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