Molecular studies were performed to identify and characterize the human herpesvirus-6 (HHV-6) genes that can activate the Human immunodeficiency virus (HIV) promoter. Members of the herpesvirus family are frequently associated with acquired immunodeficiency syndrome (AIDS). HHV-6 was initially isolated from patients with AIDS and form patients with lymphoproliferative disorders. HHV-6 productively infects many of the same cell types as HIV-1, particularly CD4 T cells and nearly every individual carries HHV-6. Co- infection of T cells with HIV-1 and HHV-6 leads to increased cytopathic effects. It is postulated that HHV-6 plays a cofactor role in hastening th development of AIDS. HHV-6 can activate the HIV-1 promoter in T-cell lines. By introducing DNA into cells in culture, we have shown that a HHV-6 gene segment, which can cause tumorigenic transformation of mouse cells and human keratinocytes, ca increase the expression of the indicator chloramphenicol acetyltransferase (CAT) gene linked to the HIV-1 promoter. This activation was mediated through a Sp1 (cellular factor) binding site present in the HIV-1 promoter and activation was dramatically reduced by oligomers designed to block the Sp1 binding sites. For efficient activation, more than one Sp1 site were required. NF-kB sites of the HIV-1 promoter were not essential for HHV-6 gene mediated activation. Our initial studies with deletion clones identified a small protein (115 amino acids) coding sequence in the HHV-6 gene segment involved in this function. Further studies are necessary to confirm the role of this protein in the activation of the HIV-1 promoter. This study is important to understand how HHV-6 could play a role in HIV pathogenesis. The project will also provide knowledge and tools for development of novel antiviral therapies and safe viral vectors for gene therapy of AIDS.

National Institute of Health (NIH)
Food and Drug Administration (FDA)
Intramural Research (Z01)
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