Unveiling the DHX15-G-patch interplay in retroviral RNA packaging

Proc Natl Acad Sci U S A. 2024 Oct;121(40):e2407990121. doi: 10.1073/pnas.2407990121. Epub 2024 Sep 25.

Abstract

We explored how a simple retrovirus, Mason-Pfizer monkey virus (M-PMV) to facilitate its replication process, utilizes DHX15, a cellular RNA helicase, typically engaged in RNA processing. Through advanced genetic engineering techniques, we showed that M-PMV recruits DHX15 by mimicking cellular mechanisms, relocating it from the nucleus to the cytoplasm to aid in viral assembly. This interaction is essential for the correct packaging of the viral genome and critical for its infectivity. Our findings offer unique insights into the mechanisms of viral manipulation of host cellular processes, highlighting a sophisticated strategy that viruses employ to leverage cellular machinery for their replication. This study adds valuable knowledge to the understanding of viral-host interactions but also suggests a common evolutionary history between cellular processes and viral mechanisms. This finding opens a unique perspective on the export mechanism of intron-retaining mRNAs in the packaging of viral genetic information and potentially develop ways to stop it.

Keywords: DEAH-box RNA helicase; DHX15; G-patch; gRNA packaging; retrovirus.

MeSH terms

  • Animals
  • Cell Nucleus / metabolism
  • Cell Nucleus / virology
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism
  • Genome, Viral
  • HEK293 Cells
  • Humans
  • Mason-Pfizer monkey virus* / genetics
  • Mason-Pfizer monkey virus* / metabolism
  • Mason-Pfizer monkey virus* / physiology
  • RNA Helicases / genetics
  • RNA Helicases / metabolism
  • RNA, Viral* / genetics
  • RNA, Viral* / metabolism
  • Virus Assembly* / genetics
  • Virus Assembly* / physiology
  • Virus Replication / genetics
  • Virus Replication / physiology

Substances

  • DEAD-box RNA Helicases
  • RNA Helicases
  • RNA, Viral
  • DHX15 protein, human