Highly pathogenic New World arenavirus infection activates the pattern recognition receptor protein kinase R without attenuating virus replication in human cells

Cheng Huang, Olga A. Kolokoltsova, Elizabeth J. Mateer, Takaaki Koma, Slobodan Paessler

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

The arenavirus family consists of several highly pathogenic viruses, including the Old World (OW) arenavirus Lassa fever virus (LASV) and the New World (NW) Junin virus (JUNV) and Machupo virus (MACV). Host response to infection by these pathogenic arenaviruses is distinct in many aspects. JUNV and MACV infections readily induce an interferon (IFN) response in human cells, while LASV infection usually triggers an undetectable or weak IFN response. JUNV induces an IFN response through RIG-I, suggesting that the host non-self RNA sensor readily detects JUNV viral RNAs (vRNAs) during infection and activates IFN response. Double-stranded- RNA (dsRNA)-activated protein kinase R (PKR) is another host non-self RNA sensor classically known for its vRNA recognition activity. Here we report that infection with NW arenaviruses JUNV and MACV, but not OW LASV, activated PKR, concomitant with elevated phosphorylation of the translation initiation factor α subunit of eukaryotic initiation factor 2 (eIF2α). Host protein synthesis was substantially suppressed in MACV- and JUNV-infected cells but was only marginally reduced in LASVinfected cells. Despite the antiviral activity known for PKR against many other viruses, the replication of JUNV and MACV was not impaired but was slightly augmented in wild-type (wt) cells compared to that in PKR-deficient cells, suggesting that PKR or PKR activation did not negatively affect JUNV and MACV infection. Additionally, we found an enhanced IFN response in JUNV- or MACV-infected PKR-deficient cells, which was inversely correlated with virus replication.

Original languageEnglish (US)
Article numbere01090-17
JournalJournal of Virology
Volume91
Issue number20
DOIs
StatePublished - Oct 1 2017

Keywords

  • Arenavirus
  • Host-pathogen interactions
  • Innate immune response
  • Interferons
  • PKR

ASJC Scopus subject areas

  • Immunology
  • Virology

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