PKR-mediated stress response enhances dengue and Zika virus replication

mBio. 2023 Oct 31;14(5):e0093423. doi: 10.1128/mbio.00934-23. Epub 2023 Sep 21.

Abstract

One of the fundamental features that make viruses intracellular parasites is the necessity to use cellular translational machinery. Hence, this is a crucial checkpoint for controlling infections. Here, we show that dengue and Zika viruses, responsible for nearly 400 million infections every year worldwide, explore such control for optimal replication. Using immunocompetent cells, we demonstrate that arrest of protein translations happens after sensing of dsRNA and that the information required to avoid this blocking is contained in viral 5'-UTR. Our work, therefore, suggests that the non-canonical translation described for these viruses is engaged when the intracellular stress response is activated.

Keywords: PKR; Zika virus; dengue virus; innate immunity; protein translation.

MeSH terms

  • A549 Cells
  • Animals
  • Chlorocebus aethiops
  • Dengue / immunology
  • Dengue / virology
  • Dengue Virus* / physiology
  • Eukaryotic Initiation Factor-2 / metabolism
  • Gene Deletion
  • Humans
  • Protein Biosynthesis / genetics
  • Protein Biosynthesis / immunology
  • RNA, Double-Stranded / metabolism
  • Stress, Physiological* / genetics
  • Stress, Physiological* / immunology
  • Vero Cells
  • Virus Replication* / genetics
  • Virus Replication* / immunology
  • Zika Virus Infection / immunology
  • Zika Virus Infection / virology
  • Zika Virus* / physiology
  • eIF-2 Kinase* / genetics
  • eIF-2 Kinase* / metabolism

Substances

  • eIF-2 Kinase
  • Eukaryotic Initiation Factor-2
  • RNA, Double-Stranded