AUTHOR=Kim Jung-Eun , Kim Young-Eui , Stinski Mark F. , Ahn Jin-Hyun , Song Yoon-Jae 

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

JOURNAL=Frontiers in Microbiology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2017.01854

DOI=10.3389/fmicb.2017.01854

ISSN=1664-302X

ABSTRACT=<p>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 <italic>IFNB1</italic> and <italic>CXCL10</italic>. Taken together, this study demonstrates the existence of a post-translational regulation of STING by HCMV IE86 protein.</p>