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.