) Kaposi's Sarcoma (KS) is a soft tissue tumor most commonly found in individuals with AIDS and immunodeficiency. Recent studies have identified a new human herpesvirus, Kaposi's sarcoma associated herpesvirus (KSHV) or Human herpesvirus-8 (HHV-8), found in almost all KS tissues and body-cavity based lymphomas. Despite the close relationship between the presence of KSHV sequence and KS, it is possible that KSHV may be a passenger virus reactivated in immunosuppressed patients. It is also difficult to explain the disproportional association between AIDS and KS, and the role HIV-1 plays in the development of KS. Our laboratory has long standing interest in studying potential interactions between HIV-1 and human herpesviruses. We have recently found that HIV-1 tat protein mononuclear cells of patients infected by HIV-1. Therefore, tat may play a role in KS development by activating KSHV replication and provides the vital link between these two viruses affects their pathogenesis in the manifestation of AIDS and KS. Our immediate approach is to determine the molecular mechanism involved in tat activation of KSHV, identify the KSHV genes, and determine if bi-directional interaction between these two viruses occurs.
Our specific aims are: 1) to determine the KSHV genes and the mechanism involved in tat activation; 2) to determine whether KSHV stimulates HIV-1 replication and identify the viral genes involved: 3) to determine the relationship between tat, KSHV and cytokines expression in KS tissues. This study should lead to a better understanding of the roles that HIV and KSHV played in KS, the viral and cellular genes involved in HIV-KSHV interaction, and how this interaction affects their disease pathogenesis.
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