Zika virus non-coding RNAs antagonize antiviral responses by PKR-mediated translational arrest.

Autor:	Pallarés HM; Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires IIBBA-CONICET, Ciudad Autónoma de Buenos Aires, Argentina., González López Ledesma MM; Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires IIBBA-CONICET, Ciudad Autónoma de Buenos Aires, Argentina., Oviedo-Rouco S; Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires IIBBA-CONICET, Ciudad Autónoma de Buenos Aires, Argentina., Castellano LA; Stowers Institute for Medical Research, Kansas City, MO, USA., Costa Navarro GS; Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires IIBBA-CONICET, Ciudad Autónoma de Buenos Aires, Argentina., Fernández-Alvarez AJ; Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires IIBBA-CONICET, Ciudad Autónoma de Buenos Aires, Argentina., D'Andreiz MJ; Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires IIBBA-CONICET, Ciudad Autónoma de Buenos Aires, Argentina., Aldas-Bulos VD; Stowers Institute for Medical Research, Kansas City, MO, USA., Alvarez DE; Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín-CONICET, Buenos Aires, Argentina., Bazzini AA; Stowers Institute for Medical Research, Kansas City, MO, USA.; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, USA., Gamarnik AV; Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires IIBBA-CONICET, Ciudad Autónoma de Buenos Aires, Argentina.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2024 Oct 14; Vol. 52 (18), pp. 11128-11147.
DOI:	10.1093/nar/gkae507
Abstrakt:	Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that causes severe outbreaks in human populations. ZIKV infection leads to the accumulation of small non-coding viral RNAs (known as sfRNAs) that are crucial for evasion of antiviral responses and for viral pathogenesis. However, the mechanistic understanding of how sfRNAs function remains incomplete. Here, we use recombinant ZIKVs and ribosome profiling of infected human cells to show that sfRNAs block translation of antiviral genes. Mechanistically, we demonstrate that specific RNA structures present in sfRNAs trigger PKR activation, which instead of limiting viral replication, enhances viral particle production. Although ZIKV infection induces mRNA expression of antiviral genes, translation efficiency of type I interferon and interferon stimulated genes were significantly downregulated by PKR activation. Our results reveal a novel viral adaptation mechanism mediated by sfRNAs, where ZIKV increases its fitness by repurposing the antiviral role of PKR into a proviral factor. (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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