HHV-8 is thought to be the etiologic agent for classical and AIDS-related Kaposi s sarcoma, as well as other lymphoproliferative diseases (LPDs) in HIV-infected humans. The investigators laboratory recently isolated and characterized a rhesus herpesvirus (RhHV) that is closely related to HHV-8. RhHV was isolated from bone marrow of a SIV-infected macaque that developed LPD and is capable of lytic replication in primary rhesus cell culture. In the proposal, the investigator proposes to examine the consequences of co-infecting rhesus macaques with RhHV and various SIV isolates to elucidate whether an HHV-8 macaque homologue is capable of inducing LPD in SIV-infected macaques.
Specific aim 1 will further define the genetic relatedness of RhHV to HHV-8 and define viral genes that might by responsible for the transformed phenotype of B lymphocytes obtained from lymphoid malignancies in HIV-infected humans.
Specific aim 2 will define in vivo conditions for the induction of viral mediated LPD in immunodeficient macaques through analysis of virus load and lymphocyte population analysis as well as examination of tissues with LPD for the presence of virus by in situ hybridization and immunohistochemical staining for particular viral antigens. Since HHV-8 is present in a high percentage of AIDS-associated malignancies, an understanding of how closely related gamma herpesvirus can induce LPD in an animals model of AIDS is essential for furthering our knowledge of viral-induced LPD in AIDS.
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