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.
Garzino-Demo
A
A
Laboratory of Biology, National Cancer Institute Bethesda, MD 20892, USA.
Chen
M
M
Lusso
P
P
Berneman
Z
Z
DiPaolo
J A
JA
D015756:Genes, tat; D016679:Genome, Viral; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D006367:HeLa Cells; D015654:Herpesvirus 6, Human / Q000235:genetics*; D006801:Humans; D019169:Jurkat Cells; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured