| Literature DB >> 30308158 |
Arabinda Nayak1, Dong Young Kim2, Michael J Trnka3, Craig H Kerr4, Peter V Lidsky5, David J Stanley3, Brianna Monique Rivera5, Kathy H Li3, Alma L Burlingame3, Eric Jan4, Judith Frydman6, John D Gross3, Raul Andino7.
Abstract
The dicistrovirus, Cricket paralysis virus (CrPV) encodes an RNA interference (RNAi) suppressor, 1A, which modulates viral virulence. Using the Drosophila model, we combined structural, biochemical, and virological approaches to elucidate the strategies by which CrPV-1A restricts RNAi immunity. The atomic resolution structure of CrPV-1A uncovered a flexible loop that interacts with Argonaute 2 (Ago-2), thereby inhibiting Ago-2 endonuclease-dependent immunity. Mutations disrupting Ago-2 binding attenuates viral pathogenesis in wild-type but not Ago-2-deficient flies. CrPV-1A also contains a BC-box motif that enables the virus to hijack a host Cul2-Rbx1-EloBC ubiquitin ligase complex, which promotes Ago-2 degradation and virus replication. Our study uncovers a viral-based dual regulatory program that restricts antiviral immunity by direct interaction with and modulation of host proteins. While the direct inhibition of Ago-2 activity provides an efficient mechanism to establish infection, the recruitment of a ubiquitin ligase complex enables CrPV-1A to amplify Ago-2 inactivation to restrict further antiviral RNAi immunity.Entities:
Keywords: Ago-2; Ago-2 degradation; CrPV; E3 ligase; RNAi; RNAi suppressor; antiviral immunity; insects
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Year: 2018 PMID： 30308158 PMCID： PMC6450077 DOI： 10.1016/j.chom.2018.09.006
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 21.023