REGULATION OF STAT-1 BY HPV-31 GENE PRODUCTS

Northwestern University, Evanston IL

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Abstract

Human papillomaviruses (HPVs) are small DNA tumor viruses that infect cutaneous or mucosal epithelia tissue and induce hyperproliferative lesions. The "high risk" HPVs are associated with the development of anogenital cancers. To better understand the pathogenesis of HPV, microarray analysis was used to examine the alteration at the transcriptional level in cells latently infected with the high risk type HPV 31. The most significant changes identified were the down-regulation of a subset of interferon inducible genes, including the major regulator of the interferon signaling pathway, Stat-1. This proposal is aimed at understanding the mechanism of the suppression of interferon inducible genes, especially Stat-1, upon HPV infection. A series of experiments are proposed to identify individual viral genes that are responsible for the suppression of Stat-1. This study will thus elucidate the mechanisms of immune evasion by HPV31 via Stat-1 suppression.