HUMAN CYTOMEGALOVIRUS PRODUCT UL44 DOWN-REGULATES THE TRANSACTIVATIONOF HIV-1 LONG TERMINAL REPEAT

Objective: Human cytomegalovirus (HCMV) is often isolated from HIV-1-i nfected patients and the two viruses can infect the same cell type giv ing rise to direct bidirectional interactions. Whereas the long termin al repeat (LTR) transactivation ability of HCMV immediate early gene ( IE1/IE2) is well documented, no information is available on the possib le role of other HCMV proteins. In this study, the activity of ppUL44, an early DNA-binding protein, on HIV LTR transactivation was investig ated. Methods: HIV LTR transactivation by ppUL44 in presence or absenc e of HIV-1 Tat and HCMV IE1/IE2 was determined in J-Jhan and U973 cell s through transient transfection experiments with a series of differen t expression vectors. Some experiments were also performed on U373-MG astrocytoma cells permanently transfected with UL44 or with another HC MV gene used as a control (UL55). Results: The basal transactivation a ctivity of the HIV LTR was not influenced by the presence of ppUL44. O n the contrary, the transactivation observed in the presence of Tat, I E1/IE2 or both factors in synergy was strongly downregulated by ppUL44 in a dose-dependent manner. Deletion constructs of ppUL44 demonstrate d that the region of the molecule responsible for the inhibition of th e LTR is located within the last 114 amino acids at the carboxyl-termi nal region. Conclusions: The results obtained indicate that within the last 114 amino acids of ppUL44 there is a domain that has a negative effect on the ability of HIV-1 LTR to be activated by both its autolog ous transactivator Tat and the heterologous transactivator HCMV IE1/IE 2 functioning individually or synergistically. (C) 1998 Rapid Science Ltd.