ANTI-HIV VIRAL INTERFERENCE INDUCED BY RETROVIRAL VECTORS EXPRESSING A NONPRODUCER HIV-1 VARIANT

A Hut-78 cell clone (F12) harboring a nonproducer human immunodeficien cy virus (HIV-1) variant shows complete resistance to HIV-1 or HIV-2 s uperinfection. The F12-HIV provirus produces an altered HIV-1 protein pattern and cannot generate even immature viral particles. We demonstr ated that HeLa CD4+ cells transfected with the F12-HIV genome resist H IV superinfection through a CD4-independent mechanism. As F12-HIV appe ars to be a useful system to induce anti-HIV intracellular immunizatio n, we constructed various retroviral vectors containing the F12-HIV ge nome, modified by elimination of the F12 3' LTR and part of its nef ge ne, inserted 'antisense' with respect to the Moloney murine leukemia v irus 5' LTR. Here we show that recombinant retroviral particles carryi ng the N2/F12-HIV nef- (as) construct can stably transduce both CEMss human cells and primary human peripheral blood lymphocytes, inducing t he expression of the F12-HIV genome. These results could open the way to an anti-AIDS gene therapy strategy based on F12-HIV-induced intrace llular immunization.