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Zika Virus Non-Coding RNAs Antagonize Antiviral Responses by PKR-Mediated Translational Arrest (Ribo-Seq)

GSE254253 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2024/04/28 Platform GPL30173
Summary
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.
Published in
Zika virus non-coding RNAs antagonize antiviral responses by PKR-mediated translational arrest
Pallarés HM, González López Ledesma MM, Oviedo-Rouco S et al. · Nucleic acids research 2024 · PMID 38917323 · doi:10.1093/nar/gkae507
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Direct links to NCBI, no account and no request form: the whole study as GSE254253_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 6 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1069085 and SRA study SRP486019. Searching any of these in the dataset finder brings you back here.

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