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Journal of Virology, February 2000, p. 2052-2056, Vol. 74, No. 4
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Herpes Simplex Virus ICP0 Mutants Are Hypersensitive to Interferon

Karen L. Mossman, Holly A. Saffran, and James R. Smiley*

Department of Medical Microbiology & Immunology, University of Alberta, Edmonton, Alberta, Canada T6G 2H7

Received 5 October 1999/Accepted 18 November 1999

Interferon (IFN) is an important immune system molecule capable of inducing an antiviral state within cells. Herpes simplex virus type 1 (HSV-1) replication is somewhat reduced in tissue culture in the presence of IFN, presumably due to decreased viral transcription. Here, we show mutations that inactivate immediate-early (IE) gene product ICP0 render HSV-1 exquisitely sensitive to IFN inhibition, resulting in greatly decreased levels of viral mRNA transcripts and the resulting polypeptides and a severe reduction in plaque formation ability. Mutations in other HSV-1 genes, including the genes coding for virion transactivator VP16 and the virion host shutoff protein vhs, IE gene ICP22, and the protein kinase UL13 gene, do not increase the IFN sensitivity of HSV-1. Interestingly, ICP0 mutants demonstrate the same level of sensitivity to IFN as wild-type virus on U2OS cells, an osteosarcoma cell line that is known to complement mutations in ICP0 and VP16. Thus, in some cell types, functional ICP0 is required for HSV-1 to efficiently bypass the inhibitory effects of IFN in order to ensure its replication. The significance of this link between ICP0 and IFN resistance is discussed.

* Corresponding author. Mailing address: Department of Medical Microbiology & Immunology, 1-41, Medical Sciences Bldg., University of Alberta, Edmonton, Alberta, Canada T6G 2H7. Phone: (780) 492-2308. Fax: (780) 492-7521. E-mail: jim.smiley{at}ualberta.ca.

Journal of Virology, February 2000, p. 2052-2056, Vol. 74, No. 4
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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