Essential role of vif in establishing productive HIV-1 infection in peripheral blood T lymphocytes and monocyte/macrophages.
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.
Gabuzda
D H
DH
Division of Human Retrovirology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Li
H
H
Lawrence
K
K
Vasir
B S
BS
Crawford
K
K
Langhoff
E
E
D002460:Cell Line; D002478:Cells, Cultured; D004279:DNA, Viral / Q000737:chemistry; D016346:Gene Products, vif / Q000235:genetics / Q000502:physiology*; D016679:Genome, Viral; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008264:Macrophages / Q000382:microbiology*; D009000:Monocytes / Q000382:microbiology*; D009154:Mutation; D016366:Open Reading Frames; D011533:Proviruses / Q000235:genetics / Q000502:physiology; D012194:RNA-Directed DNA Polymerase / Q000032:analysis; D013601:T-Lymphocytes / Q000382:microbiology*; D014162:Transfection; D014779:Virus Replication; D054320:vif Gene Products, Human Immunodeficiency Virus
D004279:DNA, Viral; D016346:Gene Products, vif; D016655:HIV Core Protein p24; D054320:vif Gene Products, Human Immunodeficiency Virus; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase