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Journal of Virology, July 2006, p. 6345-6356, Vol. 80, No. 13
0022-538X/06/$08.00+0     doi:10.1128/JVI.00554-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Suppression of the Interferon-Mediated Innate Immune Response by Pseudorabies Virus

Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544

Received 16 March 2006/ Accepted 11 April 2006

Pseudorabies virus (PRV) is an alphaherpesvirus related to the human pathogens herpes simplex virus type 1 (HSV-1) and varicella-zoster virus. PRV is capable of infecting and killing a wide variety of mammals. How it avoids innate immune defenses in so many hosts is not understood. While the anti-interferon (IFN) strategies of HSV-1 have been studied, little is known about how PRV evades the IFN-mediated immune response. In this study, we determined if wild-type PRV infection can overcome the establishment of a beta interferon (IFN-ß)-induced antiviral state in primary rat fibroblasts. Using microarray technology, we found that the expression of a subset of genes normally induced by IFN-ß in these cells was not induced when the cells were simultaneously infected with a wild-type PRV strain. Expression of transcripts associated with major histocompatibility complex class I antigen presentation and NK cell activation was reduced, while transcripts associated with inflammation either were unaffected or were induced by viral infection. This suppression of IFN-stimulated gene expression occurred because IFN signal transduction, in particular the phosphorylation of STAT1, became less effective in PRV-infected cells. At least one virion-associated protein is involved in inhibition of STAT1 tyrosine phosphorylation. This ability to disarm the IFN-ß response offers an explanation for the uniform lethality of virulent PRV infection of nonnatural hosts.

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