Human immunodeficiency virus type 2 long terminal repeat: Analysis of regulatory elements

Abstract

The long terminal repeats (LTRs) of the human immunodeficiency virus type 2 (HIV-2) and a related simian immunodeficiency virus (SIV(mac)) contain cis-acting positive regulatory elements upstream and the major transactivator gene (tat) response element and a possible negative regulatory element downstream of the transcriptional initiation site. The tat response element of HIV-2 and of SIV(mac) was more complex than that of HIV-1. Two structurally similar subelements within the HIV-2 tat response element could be identified. Both of these subelements were required for optimal transactivation by the HIV-2 tat gene product. Either of these subelements, however, was sufficient for transactivation by the HIV-1 tat gene product. These observations provide an explanation for the poor transactivation of HIV-1 LTR-directed gene expression by the HIV-2 tat gene product since the HIV-1 LTR contains an analog of only one of the HIV-2 subelements. The HIV-2 tat gene product also affected the function of the upstream elements, including enhancer activity. The response of these cis elements of HIV-2 to transactivation by HIV-2/SIV(mac) and HIV-1 tat gene differed somewhat in virus-infected and tat gene transfected cells, probably related to the differences in the effective concentration of the tat gene products and/or other viral or cellular factors. The steady-state levels of HIV-2 LTR-linked gene transcripts were much higher in the presence of HIV-2, SIV(mac), and HIV-1 tat genes than in their absence, suggesting transcriptional modulation as a mechanism for tat gene function.