Cellular and viral specificities of human immunodeficiency virus type 1 vif protein

The vif gene of human immunodeficiency virus type 1 (HTV-1) greatly enhance s the infectivity of HIV-1 virions that are released from cells classified as nonpermissive (e.g., lymphocytes, macrophages, and H9 leukemic T cells) but is irrelevant in permissive cells (e.g., HeLa or COS cells), Recently, it was reported that vif expression in nonpermissive cells dramatically inc reases infectivity not only of HIV-1 but also of other enveloped viruses, i ncluding murine leukemia viruses (MLVs), This was surprising in part becaus e MLVs and other murine retroviruses lack vif genes yet replicate efficient ly in T lymphocytes. To investigate these issues, we first developed improv ed methods for producing substantial quantities of HIV-1 virions with vif d eletions from healthy H9 cells. These virions had approximately the same am ounts of major core proteins and envelope glycoproteins as the control wild -type virions but were only approximately 1% as infectious. We then produce d H9 cells that contained wild-type or vif deletion HIV-gpt proviruses, whi ch lack a functional env gene. After superinfection with either xenotropic or amphotropic MLVs, these cells released HIV-gpt virions pseudotyped with an MLV envelope plus replication-competent MLV, Interestingly, the pseudoty ped HIV-gpt (vif deletion) virions were noninfectious, whereas the MLV viri ons simultaneously released from the same H9 cells were Fully infectious. T hese results strongly suggest that the Vif protein functions in a manner th at is both cell specific and at least substantially specific for HIV-1 and related lentiviruses, In addition, these results confirm that vif deletion HIV-1 virions from nonpermissive cells are blocked at a postpenetration sta ge of the infection pathway.