ENHANCEMENT OF TAT-INDUCED TRANSACTIVATION OF THE HIV-1 LTR BY 2 GENOMIC FRAGMENTS OF HHV-6

Clinical and experimental observations suggest that human herpesvirus- 6 (HHV-6), a T-lymphotropic herpesvirus, may act as a cofactor in the acquired immunodeficiency syndrome (AIDS). Moreover, a possible role o f HHV-6 in the increased incidence and severity of cervical carcinoma in human immunodeficiency virus (HIV)-infected women was suggested by the recent observation that HHV-6 can infect cervical carcinoma cells, accelerating their tumorigenicity in vivo. Therefore, the ability of four HHV-6 genomic clones derived from HHV-6 to transactivate the long terminal repeat (LTR) of HIV-1 in two cervical carcinoma cell lines a nd in a T-lymphoid cell line was tested. Two HHV-6 clones, pZVH-14 and pZVB-70, which were previously shown to increase the expression of hu man papillomavirus (HPV)-transforming genes, were, per se, weak transa ctivators of the HIV-1 LTR. However, an increased effect occurred when these clones were combined with the HIV-1 transactivator TAT-1. No su ch effect was seen with two other HHV-6 clones used as controls. Analy sis with HIV-1 LTR deletion mutants indicated that this enhancing effe ct requires the presence of elements contained in both the enhancer re gion and the TAT activation region (TAR) of HIV-1. This data may have implications for the potential role of HHV-6 in AIDS and AIDS-related cervical carcinoma. (C) 1996 Wiley-Liss, Inc.