G3BP1, G3BP2 and CAPRIN1 Are Required for Translation of Interferon Stimulated mRNAs and Are Targeted by a Dengue Virus Non-coding RNA

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Dengue virus is the most prevalent arbovirus in the world and an increasingly significant public health problem. Development of vaccines and therapeutics has been slowed by poor understanding of viral pathogenesis. Especially, how the virus subverts the host interferon response, a powerful branch of the innate immune system remains the subject of debate and great interest. Dengue virus produces large quantities of a non-coding, highly structured viral RNA, termed sfRNA, whose function in viral replication is elusive but has been linked in related viruses to inhibition of the interferon response. Nonetheless the mechanisms involved are yet to be characterized. Here, we show that dengue virus 2 sfRNA targets and antagonizes a set of host RNA-binding proteins G3BP1, G3BP2 and CAPRIN1, to interfere with translation of antiviral interferon-stimulated mRNAs. This activity impairs establishment of the antiviral state, allowing the virus to replicate and evade the interferon response. While this particular mechanism was not conserved among other flaviviruses, we believe it is highly relevant for dengue virus 2 replication and pathogenesis. Taken together, our results highlight both new layers of complexity in the regulation of the innate immune response, as well as the diversity of strategies flaviviruses employ to counteract it.

Vyšlo v časopise: G3BP1, G3BP2 and CAPRIN1 Are Required for Translation of Interferon Stimulated mRNAs and Are Targeted by a Dengue Virus Non-coding RNA. PLoS Pathog 10(7): e32767. doi:10.1371/journal.ppat.1004242
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004242

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