Enhancement of TAT-induced transactivation of the HIV-1 LTR by two 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 of 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 and 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 human papillomavirus (HPV)‐transforming genes, were, per se, weak transactivators of the HIV‐1 LTR. However, an increased effect occurred when these clones were combined with the HIV‐1 transactivator TAT‐1. No such effect was seen with two other HHV‐6 clones used as controls. Analysis with HIV‐1 LTR deletion mutants indicated that this enhancing effect requires the presence of elements contained in both the enhancer region 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. © 1996 Wiley‐Liss, Inc.