Essential role of vif in establishing productive HIV-1 infection in peripheral blood T lymphocytes and monocyte/macrophages

Abstract

The role of vif during the establishment of human immunodeficiency virus type 1 (HIV-1) infection of peripheral blood T lymphocytes and monocyte/macrophages was investigated using vif mutants of three HIV-1 proviral DNAs. Vif was found to be essential for the establishment of productive HIV-1 infection in peripheral blood T lymphocytes after cell-free infection with HXB2 and DFCI-HD, a vpr-positive, vpu-positive, nef-positive derivative of HXB2. A chimeric HIV-1 provirus in which the T-cell line-tropic env sequences in DFCI-HD were replaced with the macrophagetropic env of the ADA strain was constructed for studies on the role of vif during the establishment of HIV-1 infection in primary monocyte/macrophages. These studies showed that vif is also essential for the initiation of productive HIV-1 infection in primary monocyte/macrophage cultures after cell-free virus transmission. The DFCI-HD-ADA virus was shown to replicate in the CD4+ T-cell line Molt 4 clone 8 but not in other T-cell or monocytic cell lines, as previously shown for another macrophagetropic strain YU-2 (1), suggesting that this cell line may be useful for future studies on at least some macrophagetropic strains of HIV-1. The finding that vif is essential for the establishment of productive HIV-1 infection in primary T lymphocytes and monocyte/macrophages suggests that vif may be required for HIV-1 transmission and disease pathogenesis during natural infections and thus may be a good target for prophylactic or therapeutic intervention.