Veterinary and Biomedical Sciences, Department of


Date of this Version

March 1994


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


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.