Cellular factors regulate transactivation of human immunodeficiency virus type 1

Abstract

It is hypothesized that the immediate-early (IE) gene products of human cytomegalovirus (CMV) and the transactivator (TAT) of human immunodeficiency virus type 1 (HIV-1) regulate HIV-1 gene expression through mechanisms involving host cell factors. By using transient transfection assays with the gene for chloramphenicol acetyltransferase (CAT) under the transcriptional control of the HIV-1 long terminal repeat (LTR), we examined transactivation of the LTR by plasmids that express either the HIV-1 gene for TAT or human CMV IE. The ratio of the level of transactivation by CMV IE to the level of transactivation by TAT varied up to 1,000-fold between cell types. The difference in the activities of these transactivators in various cell types was not a consequence of differential expression of the transactivator gene. Analysis of RNA species initiated in the HIV-1 LTR supports the conclusion that cellular factors regulate the level of elongation of the transcription complex on the LTR. Furthermore, evidence that in some cell types the predominant mechanism of transactivation by HIV-1 TAT involves posttranscriptional processes is presented.