Essential role for the dsRNA-dependent protein kinase PKR in innate immunity to viral infection

Siddharth Balachandran, Paul C. Roberts, Laura E. Brown, Ha Truong, Asit K. Pattnaik, David R. Archer, Glen N Barber

Research output: Contribution to journalArticle

334 Citations (Scopus)

Abstract

The double-stranded (ds) RNA-dependent protein kinase PKR is considered to play an important role in interferon's (IFN's) response to viral infection. Here, we demonstrate that mice lacking PKR are predisposed to lethal intranasal infection by the usually innocuous vesicular stomatitis virus, and also display increased susceptibility to influenza virus infection. Our data indicate that in normal cells, PKR primarily prevents virus replication by inhibiting the translation of viral mRNAs through phosphorylation of elF2α, while concomitantly assisting in the production of autocrine IFN and the establishment of an antiviral state. These results show that PKR is an essential component of innate immunity that acts early in host defense prior to the onset of IFN counteraction and the acquired immune response.

Original languageEnglish
Pages (from-to)129-141
Number of pages13
JournalImmunity
Volume13
Issue number1
StatePublished - Dec 10 2000

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eIF-2 Kinase
Virus Diseases
Innate Immunity
Interferons
Vesicular Stomatitis
Double-Stranded RNA
Protein Biosynthesis
Virus Replication
Orthomyxoviridae
Antiviral Agents
Phosphorylation
Viruses
Infection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Balachandran, S., Roberts, P. C., Brown, L. E., Truong, H., Pattnaik, A. K., Archer, D. R., & Barber, G. N. (2000). Essential role for the dsRNA-dependent protein kinase PKR in innate immunity to viral infection. Immunity, 13(1), 129-141.

Essential role for the dsRNA-dependent protein kinase PKR in innate immunity to viral infection. / Balachandran, Siddharth; Roberts, Paul C.; Brown, Laura E.; Truong, Ha; Pattnaik, Asit K.; Archer, David R.; Barber, Glen N.

In: Immunity, Vol. 13, No. 1, 10.12.2000, p. 129-141.

Research output: Contribution to journalArticle

Balachandran, S, Roberts, PC, Brown, LE, Truong, H, Pattnaik, AK, Archer, DR & Barber, GN 2000, 'Essential role for the dsRNA-dependent protein kinase PKR in innate immunity to viral infection', Immunity, vol. 13, no. 1, pp. 129-141.
Balachandran S, Roberts PC, Brown LE, Truong H, Pattnaik AK, Archer DR et al. Essential role for the dsRNA-dependent protein kinase PKR in innate immunity to viral infection. Immunity. 2000 Dec 10;13(1):129-141.
Balachandran, Siddharth ; Roberts, Paul C. ; Brown, Laura E. ; Truong, Ha ; Pattnaik, Asit K. ; Archer, David R. ; Barber, Glen N. / Essential role for the dsRNA-dependent protein kinase PKR in innate immunity to viral infection. In: Immunity. 2000 ; Vol. 13, No. 1. pp. 129-141.
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