Role of ISG54 in Response to Viral Infection

State University New York Stony Brook, Stony Brook NY

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Abstract

An effective innate immune response is essential for survival of pathogenic infections. Interferons[unreadable] are critical cytokine mediators of cellular defense, and they are produced in response to viral infections[unreadable] and act on neighboring cells to confer resistance to infection. Interferons bind to cell surface receptors[unreadable] and stimulate a signal transduction pathway to the nucleus that induces the transcription of a subset of[unreadable] genes. The products of the newly induced genes act coordinately to establish an effective host[unreadable] defense. Although a few genes have been identified that exhibit antiviral activity, these are not[unreadable] sufficient to account for the antiviral effects of interferon. The infected cell produces many proteins in[unreadable] addition to interferon, and these proteins may also function to curb dissemination of the virus. The[unreadable] roles of many genes induced in the infected cell remain to be determined. One gene that is induced in[unreadable] response to viral infection and to interferon is called interferon stimulated gene factor 54 (ISG54).[unreadable] ISG54 appears to be a member of a family of proteins that possess tetratricopeptide repeats.[unreadable] However, little else is known of the function of ISG54. Our preliminary data suggest that ISG54[unreadable] decreases cell viability, and in this way it may contribute to reduction of viral dissemination. The broad[unreadable] goal for this exploratory/developmental research proposal is to initiate studies that will elucidate the[unreadable] mechanism by which ISG54 expression contributes to innate immunity.[unreadable] Our approaches will include analyses to 1) Determine the cellular localization of ISG54, 2)[unreadable] Establish the effect of ISG54 on cell viability, 3) Identify interacting partners of ISG54, and 4) Evaluate[unreadable] the role of ISG54 in viral defense. The transcriptional induction of ISG54 in response to virus,[unreadable] interferon, DNA damage, and Toll-receptor signaling indicates that it plays a critical role in the cellular[unreadable] defense response. Knowledge of the function of ISG54 may provide a new avenue to intervene and[unreadable] treat infections.[unreadable]