The GGTCA palindrome and cognate cellular factors in trans-regulation of human immunodeficiency virus long terminal repeat by herpes simplex virus

Abstract

Molecular interactions between herpes simplex virus type 1 (HSV-1) and human immunodeficiency virus (HIV) were investigated in the promonocytic cell line U937. HSV-l-mediated activation was observed in transient expression assays with hybrid constructions containing the HIV long terminal repeat (LTR)-directed chloramphenicol aeetyltransferase gene. Comparison of constructions that differ in the GGTCA palindrome located within the negative regulatory region of the LTR revealed four-to eightfold lower activation levels for the wild-type as compared to the mutant sequence. Three protein species, 37K, 59K/64K and 75K, that bind to the wild-type GGTCA palindrome were resolved in nuclear extracts of uninfected U937 cells by gel retardation and u.v.-crosslinking experiments. The 37K protein did not bind to the mutant palindrome sequence. However, a distinct 120K protein was detected. The 37K and 59K/64K binding proteins were not resolved in similar experiments performed with nuclear extracts from HSV-l-infected U937 cells but there was a novel p50 species that binds only to the wild-type palindrome sequence. These findings raise the possibility that interaction of these proteins at the GGTCA palindrome is involved in HSV-l-mediated regulation of the HIV LTR in U937 cells.

Transcriptional Activation of Human Immunodeficiency Virus Type 1 by Herpesvirus Infection: An in vivo Footprinting Study

“…Activation of HIV-1 in T-cellsand macrophages is associ ated with the induction of proteins binding to the enhanc er region and the magnitude of response depends on the presence of intact k B and Spl sites [8][9][10], In HSV-1 infected T cells, the region near the transcriptional initia tion site is also involved in the LTR activation process [9. 11], In contrast, in monocytic cells, the LTR activation effect is mediated by a responsive element located at posi tions -353 to -327 within the negative regulatory element [12]. Finally, in Jurkat T cells expressing the HIV-1 tat gene, the transactivation response is again kB site inde pendent, although no single element conferring HSV-1 inducibility has been identified [13].…”