Identification and Characterization of a Human Herpesvirus 6 Gene Segment Capable of Transactivating the Human Immunodeficiency Virus Type 1 Long Terminal Repeat in an Spl Binding Site-Dependent Manner

Authors

• Jinhai Wang, Division of Viral Products, Center for Biologics Evaluation and Research, Bethesda, Maryland
• Clinton J. Jones, University of Nebraska - LincolnFollow
• Michael Norcross, Division of Viral Products, Center for Biologics Evaluation and Research, Bethesda, Maryland
• Ernst Bohnlein, Vienna International Research Cooperation Center, University of Vienna, Vienna, Austria
• Abdur Razzaque, Division of Viral Products, Center for Biologics Evaluation and Research, Bethesda, Maryland

Document Type

Article

Date of this Version

March 1994

Comments

Published in JOURNAL OF VIROLOGY, Mar. 1994, p. 1706-1713 Vol. 68, No. 3. Copyright 1994. Used by permission.

Abstract

The human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) is transactivated by various extracellular signals and viral cofactors that include human herpesviruses. These transactivators are capable of transactivating the HIV-1 LTR through the transactivation response element, NF-KB, or other regulatory binding elements. Human herpesvirus 6 (HHV-6) is a potential cofactor of HIV-1. Here, we report that an HHV-6 gene segment, ZVH14, which can neoplastically transform NIH 3T3 and human keratinocytes, is capable of transactivating HIV-1 LTR chloramphenicol acetyltransferase constructs in an Spl binding site-dependent manner. Transactivation increased synergistically in the presence of multiple Spl sites and was dramatically reduced by cotransfection with oligomers designed to form triplex structures with HIV-1 LTR Spl binding sites. HIV-1 LTR NF-KB sites were not essential for ZVH14-mediated transactivation. A putative open reading frame in ZVH14, B115, which may encode a highly basic peptide consisting of 115 amino acid residues, showed transactivation capacity similar to that of ZVH14. This open reading frame also transactivated the HIV-1 LTR in an Spl site-dependent fashion in African green monkey kidney cells and human T cells. These data suggest that HHV-6 may stimulate HIV-1 replication via transactivation of Spl binding sites present in the HIV-1 promoter.