DEVELOPMENT OF HHV-8 DETECTION/NEUTRALIZATION REAGENTS

DESCRIPTION: Human herpesvirus-8 (HHV-8, also known as KSHV) has been found to be the etiogical agent of Kaposis sarcoma (KS) and other human malignancies including body cavity-based/primary effusion lymphoma (PEL) and a subset of multicentric Castleman's Disease. The entire genome sequence has been reported and the functions of numerous genes with homologies to human genes have been identified. Despite these rapid advances in our knowledge of HHV-8, little is known about the viral surface glycoproteins and the viral infection pathway due to lack of research tools. The objectives of this proposal are to identify and characterize HHV-8 glycoprotein-specific monoclonal antibodies and to determine the potential of using these antibodies to prevent the virus attachment and penetration. In Phase I of this proposal we seek (1). To identify monoclonal antibodies against HHV-8 membrane glycoproteins, (2). To characterize the HHV-8 monoclonal antibodies, and (3). To determine the effect of antibodies specific for HHV-8 glycoproteins on virus infectivity. The initial studies carried out in this proposal not only will be useful in developing research tools but also will provide significant insight for the Phase II to develop clinical diagnostic and viral infection prevention/therapeutic reagents. PROPOSED COMMERCIAL APPLICATION: HHV-8 infection is strongly associated with human Kaposi's Sarcoma and several lymphoproliferative diseases. The production of antibodies against glycoproteins to HHV-8 will provide reagents for basic science researchers investigating viral infections, as well as generate a panel of antiviral agents that can be used by clinicians to prevent viral infection in susceptible individuals.