Stimulation of the Human Immunodeficiency Virus Type 2 (HIV-2) Gene Expression by the Cytomegalovirus and HIV-2 Transactivator Gene

Human immunodeficiency virus (HIV) often causes latent infection. Transactivation by some DNA viruses has been implicated in inducing HIV-1 replication and pathogenesis. The transactivator (IE-2) gene of the human cytomegalovirus (CMV) can enhance HIV-2 as well as HIV-1 gene expression in vitro. This inducer can act in concert with the HIV-2 tat gene and T-cell activation in enhancing gene expression in human CD4⁺ lymphocytes. While the HIV-2 and HIV-1 tat genes and T-cell activators apparently employ independent modes of action, the CMV transactivator in combination with the HIV-2 tat or T-cell activators may employ a gene activation pathway with some common and some distinct components. Both HIV-2 and CMV transactivators enhance HIV-2 gene expression by transcriptional activation involving transcript initiation as well as elongation, with CMV transactivator affecting elongation more than the initiation. A significant proportion of transcripts appear to terminate prematurely in the absence of transactivators. Deletion mutation analysis of the HIV-2 long terminal repeat (LTR) suggests that the element that responds to CMV transactivation in human CD4⁺ lymphocytes is either a diffuse one or located downstream of the HIV-2 enhancer element.