Allelic variation in the effects of the nef gene on replication of human immunodeficiency virus type 1.
The effects of the viral gene nef on human immunodeficiency virus type 1 (HIV-1) replication in culture were investigated using nef alleles of the HIV-1 IIIB and ELI strains. The results demonstrate significant allelic variation in the effect of nef on virus replication in both an established human CD4+ T-cell line and primary human lymphocytes. In the context of the HXB2 virus, the ELI nef allele but not the IIIB nef allele permits initiation of efficient low-multiplicity infection in primary peripheral blood mononuclear cells, including unfractionated peripheral blood lymphocytes, T cells, and monocyte/macrophages. Within the same genetic context, the IIIB nef allele slightly retards replication of the virus in a T-cell line, whereas the ELI nef allele accelerates replication of the virus. Sequences in the IIIB and ELI genomes outside of nef also moderate the effects of nef on HIV-1 replication. nef did not appear to determine the host-cell preference of the virus. These studies may help to reconcile apparently conflicting reports on the role of nef in HIV-1 replication and suggest that HIV-1 nef may play an important role in viral pathogenesis.
Terwilliger
E F
EF
Division of Human Retrovirology, Dana-Farber Cancer Institute, Boston, MA 02115.
Langhoff
E
E
Gabuzda
D
D
Zazopoulos
E
E
Haseltine
W A
WA
D000483:Alleles; D002460:Cell Line; D002478:Cells, Cultured; D015754:Genes, nef; D014644:Genetic Variation; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D010641:Phenotype; D011533:Proviruses / Q000235:genetics / Q000502:physiology; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D015183:Restriction Mapping; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014162:Transfection; D014779:Virus Replication
D012194:RNA-Directed DNA Polymerase