Characterization of a PKR inhibitor from the pathogenic ranavirus, Ambystoma tigrinum virus, using a heterologous vaccinia virus system

Virology. 2017 Nov:511:290-299. doi: 10.1016/j.virol.2017.08.012. Epub 2017 Sep 14.

Abstract

Ambystoma tigrinum virus (ATV) (family Iridoviridae, genus Ranavirus) was isolated from diseased tiger salamanders (Ambystoma tigrinum stebbinsi) from the San Rafael Valley in southern Arizona, USA in 1996. Genomic sequencing of ATV, as well as other members of the genus, identified an open reading frame that has homology to the eukaryotic translation initiation factor, eIF2α (ATV eIF2α homologue, vIF2αH). Therefore, we asked if the ATV vIF2αH could also inhibit PKR. To test this hypothesis, the ATV vIF2αH was cloned into vaccinia virus (VACV) in place of the well-characterized VACV PKR inhibitor, E3L. Recombinant VACV expressing ATV vIF2αH partially rescued deletion of the VACV E3L gene. Rescue coincided with rapid degradation of PKR in infected cells. These data suggest that the salamander virus, ATV, contains a novel gene that may counteract host defenses, and this gene product may be involved in the presentation of disease caused by this environmentally important pathogen.

Keywords: Innate immune evasion; PKR; Pathogenesis factor; dsRNA; eIF2α.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Ambystoma / virology
  • Animals
  • Arizona
  • Gene Expression
  • Genetic Vectors
  • Host-Pathogen Interactions
  • Immune Evasion
  • Protein Kinase Inhibitors / metabolism*
  • Ranavirus / genetics
  • Ranavirus / pathogenicity*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism*
  • Vaccinia virus / genetics
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*
  • Virulence Factors / genetics
  • Virulence Factors / metabolism*
  • eIF-2 Kinase / antagonists & inhibitors*

Substances

  • Protein Kinase Inhibitors
  • Recombinant Proteins
  • Viral Proteins
  • Virulence Factors
  • eIF-2 Kinase