GENETIC INTERACTION OF HUMAN HERPESVIRUS-6 WITH HIV-1

这个项目的目标是识别和描述人类

he objective of this project is to identify and characterize the human herpesvirus-6 (HHV-6) genes that can activate the human immunodeficiency virus type-1 (HAVE) promoter and to determine how the interactions between these two viruses occur.HHV-6 has been suggested as a cofactor in HAVE infection and in the development of AIDS, since 1) HHV-6 productively infects many of the same cell types as HIV-6 lead to increased cytopathic effects.By DNA transfection into monkey kidney cells and human T cells, we have shown that a HHV-6 gene segment ZVH14 (8.7 kb), which were found to transform mouse cells and human keratinocytes, can increase the expression of the indicator chloramphenicol acetyltransferase zCAT) gene linked to the HAVE promoter. This activation was mediated through a Sp1 (cellular factor) binding site present in the HAVE 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 HAVE promoter were not essential for HHV-6 ZVH12-mediated activation. Our studies with deletion cones of ZVH14 identified that a small open reading frame called B115, potentially encoding a 115-amino acid protein, was primarily involved in this transactivation function. Preliminary expression studies in vitro found the protein of the predicted 18r = 18 kDa. Recently, we have generated mutants of this protein by site- specific mutagenesis to confirm its role in this transactivation and HAVE replication.This study is important to better understand the role of HHV- 6 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.