THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) VIF PROTEIN IS LOCATED IN THE CYTOPLASM OF INFECTED-CELLS AND ITS EFFECT ON VIRAL REPLICATION IS EQUIVALENT IN HIV-2

The human immunodeficiency virus type 1 (HIV-1) vif gene (viral infect ivity gene) plays an important role in viral replication in vitro. We demonstrated that the Vif protein is membrane associated in HIV-1-infe cted cells and have investigated the role in viral replication of the equivalent gene in HIV-2. We constructed an HIV-2 vif minus mutant and studied its virulence and cellular tropism in vitro. Parallel experim ents were also performed with an HIV-1 vif mutant to ascertain whether the two distantly related HIV-2 and HIV-1 genes might exert the same effect on viral replication. The results indicated that both HIV-1 and HIV-2 vif minus cell-free infection was not impaired when the SupT-1 cell line was used. However, differential degrees of impairment in vir al replication were observed when other cell lines were used (Molt-3, U-937). Nevertheless, when viral production could not be detected, res cue experiments by coculture with the permissive cell line SupT-1 were generally positive, indicating that the viruses were still present in the inoculated cells. In contrast, when primary human cells (peripher al blood mononuclear cells and purified macrophages) were infected wit h HIV-1 and HIV-2 vif minus viruses no productive infection was observ ed and generally no virus was rescued by cocultivation. Thus, like in HIV-1, the vif gene of HIV-2 is crucial for viral infectivity in prima ry cells and might represent an attractive target for therapy.