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

Shanping He, Jun Zhao, Shanshan Song, Xiaojing He, Arlet Minassian, Yu Zhou, Junjie Zhang, Kevin Brulois, Yuqi Wang, Jackson Cabo, Ebrahim Zandi, Chengyu Liang, Jae U. Jung, Xuewu Zhang, Pinghui Feng

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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 invitro. 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.

Original languageEnglish (US)
Pages (from-to)134-146
Number of pages13
JournalMolecular Cell
Volume58
Issue number1
DOIs
StatePublished - Apr 2 2015

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

He, S., Zhao, J., Song, S., He, X., Minassian, A., Zhou, Y., Zhang, J., Brulois, K., Wang, Y., Cabo, J., Zandi, E., Liang, C., Jung, J. U., Zhang, X., & Feng, P. (2015). Viral pseudo-enzymes activate RIG-I via deamidation to evade cytokine production. Molecular Cell, 58(1), 134-146. https://doi.org/10.1016/j.molcel.2015.01.036