The long term of this study is to determine the contribution of opportunistic infection to the pathogenicity of the human immunodeficiency virus type 1 (HIV-1) infection and to development of AIDS. Opportunistic infection with either viral or bacterial agents is one of the characteristic features of AIDS disease. For the evaluation of the role of these factors in development of AIDS it is essential to understand the mechanism f the interaction between HIV-1 virus and the other infectious agents. Our studies have addressed the interaction between HIV-1 and HSV-1 in terms of enhancement of HIV-1 replication. We have shown that HSV-1 infection stimulates transcriptional activity of HIV-1 LTR and induces expression of HIV-1 provirus in T cells. The HSV-1 mediated induction correlates with the binding of 55- and 85-kDa proteins to the NF -kB enhancer and 55 kDa protein (HLP-1) to the LBP-1 region of HIV-LTR. Induciton of HIV-1 provirus requires expression of HSV-1-encoded IE and DE genes but not the HSV-1 replication. In the proposed study we have focused on the molecular mechanisms by which HSV-1 up-regulates HIV-1 expression; furthermore, analysis of double infection by HSV-1 and HIV-1 in clinical samples will be performed. The proposed study has five aims; 1) Identify the molecular mechanism by which HSV-1 activates expression of HIV-1 provirus. 2) Purify HSV-1 in clinical samples will be performed. The proposed study has five aims; 1) Identify the molecular mechanism by which HSV-1 activates expression of HIV-1 provirus. 2) Purify HSV-1 specific transactivator HLP-1, clone and characterize its cDNA and determine its role in transactivation of HIV-LTR expression. 3) Identify the HSV-1 encoded gene product(s) that play an essential role in the activation/stimulation of HIV-1 encoded gene product(s) that play an essential role in the activation/stimulation of HIV-1 expression. 4) Determine whether herpes virus encoded gene product provides a helper function for productive replication of a defective HIV-1 provirus; and 5) Analyze in vitro HSV-1 and HIV-1 interaction in cells that are likely to be coinfected by these viruses in vivo. We believe that these studies will enriched our knowledge about the regulation of HIV-1 replication, identify novel mechanisms and alternative pathways involved in the regulation of HIV-1 provirus expression, as well as provide preliminary results on double infection with HIV-1 provirus expression, as well as provide preliminary results on double infection with HIV-1 and HSV-1 in vivo. The identification of different cofactors and additional mechanisms stimulating HIV-1 gene expression is fundamental for the understanding of HIV-1 pathogenicity as well as for providing a rational base for its treatment.
| Shirazi, Y; Pitha, P M (1998) Interferon downregulates CXCR4 (fusin) gene expression in peripheral blood mononuclear cells. J Hum Virol 1:69-76 |
