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Molecular interactions between human herpesviruses and the human immunodeficiency virus type 1
Abstract
Human immunodeficiency virus type 1 (HIV-1) is the etiologic agent that causes acquired immunodeficiency syndrome (AIDS). HIV-1 infected individuals frequently are infected with other viruses, including herpesviruses. Lymphocytic cells infected with both HIV-1 and human herpesvirus 6 (HHV-6), can enhance cytopathic effects caused by viral infection. Previously, several HHV-6 genes have been identified that enhance transcription of HIV-1. Since HIV-1 is capable of trans-activating herpesviruses, a reciprocal interaction between the two viruses is possible. Interactions between HIV-1 and HHV-6 were analyzed in lymphocytes. Dually infected cells show an increased HHV-6 viral titer, an increase in HHV-6 RNA, and an increase in HHV-6 protein synthesis. Similarly, T-cells transfected with the entire HIV proviral genome, or the HIV-1 trans-activator gene, tat, displayed an increase in HHV-6 viral production. The bi-directional interactions between HHV-6 and HIV-1 may accelerate depletion of CD4$\sp+$ T-cells, leading to progression to AIDS. Molecular mechanisms of tat activation include transcriptional activation of several HHV-6 promoters. However, tat-containing cell extracts did not contain factors that can bind specifically to the HHV-6 promoter DNA elements. Body cavity-based lymphoma, a rare lymphocytic tumor, and Kaposi's sarcoma (KS) associated with human herpesvirus type 8 (HHV-8) are manifestations seen in HIV-1 infected individuals with more frequency then uninfected individuals. Recent work indicates that HIV-tat is important in the pathogenesis of KS; thus, we wanted to analyze the effect of tat on HHV-8. We have found that HIV-1 tat can stimulate HHV-8 viral DNA load in two chronically infected cell lines as well as in monocytic cells from immunosuppressed individuals. The promoters of several HHV-8 genes were found to be activated by tat in transfection assays, suggesting a mechanism for up-regulation of HHV-8 by tat. These results indicate that HIV-1 may play a role in the development of HHV-8-associated diseases via tat-mediated activation of HHV-8.
Subject Area
Molecular biology|Microbiology|Immunology
Recommended Citation
Sieczkowski, Laura Michelle, "Molecular interactions between human herpesviruses and the human immunodeficiency virus type 1" (1998). ETD collection for University of Nebraska-Lincoln. AAI9829533.
https://digitalcommons.unl.edu/dissertations/AAI9829533