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Viral pseudo-enzymes activate RIG-I via deamidation to evade cytokine production.

ABSTRACT: RIG-I is a pattern recognition receptor that senses viral RNA and is crucial for host innate immune defense. Here, we describe a mechanism of RIG-I activation through amidotransferase-mediated deamidation. We show that viral homologs of phosphoribosylformylglycinamidine synthetase (PFAS), although lacking intrinsic enzyme activity, recruit cellular PFAS to deamidate and activate RIG-I. Accordingly, depletion and biochemical inhibition of PFAS impair RIG-I deamidation and concomitant activation. Purified PFAS and viral homolog thereof deamidate RIG-I in vitro. Ultimately, herpesvirus hijacks activated RIG-I to avoid antiviral cytokine production; loss of RIG-I or inhibition of RIG-I deamidation results in elevated cytokine production. Together, these findings demonstrate a surprising mechanism of RIG-I activation that is mediated by an enzyme.

SUBMITTER: He S

PROVIDER: S-EPMC4385502 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Viral pseudo-enzymes activate RIG-I via deamidation to evade cytokine production.

He Shanping S Zhao Jun J Song Shanshan S He Xiaojing X Minassian Arlet A Zhou Yu Y Zhang Junjie J Brulois Kevin K Wang Yuqi Y Cabo Jackson J Zandi Ebrahim E Liang Chengyu C Jung Jae U JU Zhang Xuewu X Feng Pinghui P

Molecular cell 20150305 1

RIG-I is a pattern recognition receptor that senses viral RNA and is crucial for host innate immune defense. Here, we describe a mechanism of RIG-I activation through amidotransferase-mediated deamidation. We show that viral homologs of phosphoribosylformylglycinamidine synthetase (PFAS), although lacking intrinsic enzyme activity, recruit cellular PFAS to deamidate and activate RIG-I. Accordingly, depletion and biochemical inhibition of PFAS impair RIG-I deamidation and concomitant activation. ...[more]

PMID: 25752576

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