) 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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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AIDS and Related Research Study Section 1 (ARRA)
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Read-Connole, Elizabeth Lee
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University of Nebraska Lincoln
Schools of Arts and Sciences
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Wen, Hui-Ju; Minhas, Veenu; Wood, Charles (2009) Identification and characterization of a new Kaposi's sarcoma-associated herpesvirus replication and transcription activator (RTA)-responsive element involved in RTA-mediated transactivation. J Gen Virol 90:944-53
Wojcicki, Janet; Mwanahamuntu, Mulindi; Minhas, Veenu et al. (2008) Mortality among HIV-1- and human herpesvirus type 8-affected mother-infant pairs in Zambia. Cancer Epidemiol Biomarkers Prev 17:2238-43
Angeletti, Peter C; Zhang, Luwen; Wood, Charles (2008) The viral etiology of AIDS-associated malignancies. Adv Pharmacol 56:509-57
Ng'andwe, Christopher; Lowe, John J; Richards, Paula J et al. (2007) The distribution of sexually-transmitted Human Papillomaviruses in HIV positive and negative patients in Zambia, Africa. BMC Infect Dis 7:77
Wood, Charles (2007) AIDS-assoicated viral oncogenesis. Overview. Cancer Treat Res 133:1-19
Yang, Zhilong; Wood, Charles (2007) The transcriptional repressor K-RBP modulates RTA-mediated transactivation and lytic replication of Kaposi's sarcoma-associated herpesvirus. J Virol 81:6294-306
St Lawrence, J S; Klaskala, W; Kankasa, C et al. (2006) Factors associated with HIV prevalence in a pre-partum cohort of Zambian women. Int J STD AIDS 17:607-13
Zhang, Hong; Hoffmann, Federico; He, Jun et al. (2006) Characterization of HIV-1 subtype C envelope glycoproteins from perinatally infected children with different courses of disease. Retrovirology 3:73
Bagasra, Omar; Patel, Deepa; Bobroski, Lisa et al. (2005) Localization of human herpesvirus type 8 in human sperms by in situ PCR. J Mol Histol 36:401-12
Wood, Charles; Harrington Jr, William (2005) AIDS and associated malignancies. Cell Res 15:947-52

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