INHIBITION OF HIV-1 EXPRESSION BY HIV-2

HIV-1 and HIV-2 are co-endemic in certain geographic areas. HIV-2 is m ore weakly pathogenic than HIV-1, and progression to AIDS occurs less frequently and over a longer period of time. Recent epidemiologic stud ies suggest that individuals infected with HIV-2 have a lower risk of HIV-1 infection. Both immune mechanisms and various modes of viral int erference have been proposed to account for these results. Our finding s, de scribed in this paper, suggest that HIV-2 inhibits HIV-1 replica tion. To study the molecular interactions between HIV-1 and HIV-2, pro viral clones were transfected alone or in combination into the human T cell line GEM. LTR-CAT indicator constructs were included for the pur pose of monitoring viral promoter activity. Viral replication in trans fected cells was monitored by p24 antigen capture assay of cell cultur e supernatants and Western blot analysis of cell extracts. HIV-2 inhib ited HIV-I replication as determined by intracellular and extracellula r p24 antigen levels. Similar results were obtained with simultaneous virus infection using HIV-1 and HIV-2, rather than transfections of pr oviral DNA. Using cotransfection of HIV-1 and HIV-2 LTR indicator gene constructs, the mechanism of inhibition was found to be suppression o f the HIV-1 LTR by HIV-2. The inhibitory effect of HIV-2 is not due to Tar-2, but appears to discriminate between the HIV-1 and HIV-2 LTRs b ased on differences in the Tar activation response element, TAR. These results suggest both a molecular mechanism for HIV-2 interference wit h HIV-1 replication and a potential molecular approach to therapy.