Human Cytomegalovirus IE2 86 kDa Protein Induces STING Degradation and Inhibits cGAMP-Mediated IFN-β Induction

Jung-Eun Kim; Young-Eui Kim; Mark F Stinski; Jin-Hyun Ahn; Yoon-Jae Song

doi:10.3389/fmicb.2017.01854

Human Cytomegalovirus IE2 86 kDa Protein Induces STING Degradation and Inhibits cGAMP-Mediated IFN-β Induction

Front Microbiol. 2017 Sep 26:8:1854. doi: 10.3389/fmicb.2017.01854. eCollection 2017.

Authors

Jung-Eun Kim¹, Young-Eui Kim², Mark F Stinski³, Jin-Hyun Ahn², Yoon-Jae Song¹

Affiliations

¹ Department of Life Science, Gachon University, Seongnam, South Korea.
² Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA, United States.
³ Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, South Korea.

Abstract

Stimulator of interferon genes (STING) is a critical signaling molecule in the innate immune response against DNA viruses by either directly sensing intracellular DNA or functioning as an adaptor molecule to activate the type I interferon (IFN) signaling pathway. We determined the functional interaction between STING and human cytomegalovirus (HCMV). A cDNA library containing 133 HCMV ORFs was screened to identify viral genes that inhibit STING-induced IFN-β promoter activation. Among the screened ORFs, UL122, which encodes the immediate-early 2 86 kDa (IE86) protein, strongly abolished STING-induced IFN-β promoter activation. Interestingly, IE86 protein facilitated the proteasome-dependent degradation of STING and inhibited 2'3'-cGAMP-mediated induction of IFNB1 and CXCL10. Taken together, this study demonstrates the existence of a post-translational regulation of STING by HCMV IE86 protein.

Keywords: HCMV; IE86; IFN; STING; cGAMP.