SIMIAN VARICELLAMODEL FOR HUMAN VZV INFECTIONS

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Varicella-zoster virus (VZV) is the etiologic agent of varicella (chickenpox) and zoster (shingles). While VZV infections are usually benign, they may be severe and life-threatening in immunocompromised individuals, especially cancer patients, transplant recipients, and AIDS patients. Unfortunately, studies on the pathogenesis of and antiviral therapy for VZV infections are hampered because VZV does not cause disease in experimental animals. However, simian varicella, which is caused by simian varicella virus (SVV), clinically and pathogenically resembles human varicella and has been shown to be an excellent animal model for human VZV infections. The overall goal of this research program is to use the simian varicella model as a means to study the pathogenesis of human VZV infections and to develop and test potential VZV subunit vaccines and other antiviral therapies. While VZV and sVV have been shown to be antigenically and genetically related, very little is known about the molecular properties or SVV. Therefore, the first 4 specific aims of this proposal are to 1) determine the structure of the SVV genome, 2) identify regions of homology between sVV and DNAs, 3) characterize the sVV glycoproteins, and 4) identify cross-reacting VZV and SVV glycoproteins. This information will provide a molecular foundation on which to base further studies on the pathogenesis of simian varicella. Specific aim #5 will determine the immune response to individual SVV glycoproteins in SVV infected monkeys and will investigate the role of these glycoproteins in inducing immunity to simian varicella. Immunization with VZV has been demonstrated to protect monkeys against subsequent challenge with sVV. Specific aim #6 will determine the immune response to the VZV glycoproteins that may be important in eliciting this immunity.