SIMIAN VARICELLA--VZV PATHOGENESIS &LATENCY

University Of Arkansas Med Scis Ltl Rock, Little Rock AR

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Abstract

DESCRIPTION (Adapted from Applicant's Abstract): Varicella zoster virus (VZV) causes varicella (chickenpox) and zoster (shingles), diseases associated with significant morbidity in children and the elderly, respectively, and severe and life_threatening infections in immunocompromised individuals. Unfortunately, our understanding of VZV pathogenesis and latency is limited due to the lack of satisfactory animal models. Simian varicella virus (SVV) causes in nonhuman primates a natural disease which clinically and pathogenically resembles human VZV infections. Based upon the antigenic and genetic relatedness of VZV and SVV and the similarities of human and simian varicella, SVV infection of nonhuman primates offers a useful animal model for human VZV infections. The P.I. has characterized the molecular properties of SVV and developed a number of specific SVV probes and reagents. The overall goal of this proposal is to utilize the simian varicella model to investigate the molecular basis of varicella pathogenesis and latency. The specific aims are: 1) To express the SVV glycoprotein E (gE), gB, and immediate early gene 62 (IE62) genes in recombinant expression vectors and to generate monospecific antisera to the expressed proteins. This antisera will be used to detect SVV antigens in ganglia and other tissues of infected monkeys. 2) To better define the incubation period of varicella by examination of SVV nasopharyngeal infection and viremia. 3) To investigate SVV infection of sensory ganglia and other tissues during primary varicella in infected monkeys. 4) To examine SVV gene expression and identify the cellular site of viral DNA and\or RNA in sensory ganglia derived from latently infected monkeys. 5) To generate a cosmid_based recombination system for SVV and to construct SVV thymidine kinase, uracil glycosylase, and glycoprotein C (gC) mutants which will be used in a future study to investigate the role of specific SVV genes in viral pathogenesis and latency.