DDX60 selectively reduces translation off viral type II internal ribosome entry sites.

Co-opting host cell protein synthesis is a hallmark of many virus infections. In response, certain host defense proteins limit mRNA translation globally, albeit at the cost of the host cell's own protein synthesis. Here, we describe an interferon-stimulated helicase, DDX60, that decreases translation from viral internal ribosome entry sites (IRESs). DDX60 acts selectively on type II IRESs of encephalomyocarditis virus (EMCV) and foot and mouth disease virus (FMDV), but not by other IRES types or by 5' cap. Correspondingly, DDX60 reduces EMCV and FMDV (type II IRES) replication, but not that of poliovirus or bovine enterovirus 1 (BEV-1; type I IRES). Furthermore, replacing the IRES of poliovirus with a type II IRES is sufficient for DDX60 to inhibit viral replication. Finally, DDX60 selectively modulates the amount of translating ribosomes on viral and in vitro transcribed type II IRES mRNAs, but not 5' capped mRNA. Our study identifies a novel facet in the repertoire of interferon-stimulated effector genes, the selective downregulation of translation from viral type II IRES elements. © 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

Citation

Mohammad Sadic, William M Schneider, Olga Katsara, Gisselle N Medina, Ashley Fisher, Aishwarya Mogulothu, Yingpu Yu, Meigang Gu, Teresa de Los Santos, Robert J Schneider, Meike Dittmann. DDX60 selectively reduces translation off viral type II internal ribosome entry sites. EMBO reports. 2022 Dec 06;23(12):e55218

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PMID: 36256515

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