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Journal of Virology, May 2003, p. 5507-5511, Vol. 77, No. 9
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.9.5507-5511.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Activation of PKR by Bunyamwera Virus Is Independent of the Viral Interferon Antagonist NSs

Hein Streitenfeld,1 Amanda Boyd,2 John K. Fazakerley,2 Anne Bridgen,3,{dagger} Richard M. Elliott,3 and Friedemann Weber1*

Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, D-79008 Freiburg, Germany,1 Laboratory for Clinical and Molecular Virology, University of Edinburgh, Summerhall, Edinburgh EH9 1QH,2 Division of Virology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G11 5JR, United Kingdom3

Received 19 September 2002/ Accepted 6 February 2003

Double-stranded RNA (dsRNA) is a by-product of viral RNA polymerase activity, and its recognition is one mechanism by which the innate immune system is activated. Cellular responses to dsRNA include induction of alpha/beta interferon (IFN) synthesis and activation of the enzyme PKR, which exerts its antiviral effect by phosphorylating the eukaryotic initiation factor eIF-2 alpha, thereby inhibiting translation. We have recently identified the nonstructural protein NSs of Bunyamwera virus (BUNV), the prototype of the family Bunyaviridae, as a virulence factor that blocks the induction of IFN by dsRNA. Here, we investigated the potential of NSs to inhibit PKR. We show that wild-type (wt) BUNV that expresses NSs triggered PKR-dependent phosphorylation of eIF-2 alpha to levels similar to those of a recombinant virus that does not express NSs (BUNdelNSs virus). Furthermore, the sensitivity of viruses in cell culture to IFN was independent of PKR and was not determined by NSs. PKR knockout mice, however, succumbed to infection approximately 1 day earlier than wt mice or mice deficient in expression of RNase L, another dsRNA-activated antiviral enzyme. Our data indicate that (i) bunyaviruses activate PKR, but are only marginally sensitive to its antiviral effect, and (ii) NSs is different from other IFN antagonists, since it inhibits dsRNA-dependent IFN induction but has no effect on the dsRNA-activated PKR and RNase L systems.

* Corresponding author. Mailing address: Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, D-79008 Freiburg, Germany. Phone: 49-761-203-6614. Fax: 49-761-203-6562. E-mail: FWEBER{at}UKL.UNI-FREIBURG.DE.

{dagger} Present address: Department of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, United Kingdom.

Journal of Virology, May 2003, p. 5507-5511, Vol. 77, No. 9
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.9.5507-5511.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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