Cooperative effects of the human immunodeficiency virus type 1 envelope variable loops V1 and V3 in mediating infectivity for T cells.
Insertion of T-cell line-tropic V3 and V4 loops from the HXB2 strain into the macrophage-tropic YU-2 envelope resulted in a virus with delayed infectivity for HUT78 and Jurkat cells compared with HXB2. Sequence analysis of viral DNA derived from long-term cultures of Jurkat cells revealed a specific mutation that changed a highly conserved Asn residue in the V1 loop of Env to an Asp residue (N-136-->D). Introduction of this mutation into clones containing a T-cell line-tropic V3 loop, either with or without a T-cell line-tropic V4 loop, resulted in viruses that replicated to high levels in Jurkat cells and peripheral blood lymphocytes. The Env proteins from these constructs were expressed with the vaccinia virus/T7 hybrid system and were found to be translated, processed, and cleaved and to bind to soluble CD4 similar to the wild-type HXB2 and YU-2 Env proteins. Env-mediated fusion with HeLa T4+ cells, however, was regulated by both the altered V1 loop and T-cell line-tropic V3 loop. These results suggest that subsequent to the initial gp120-CD4 binding event, a functional interaction can occur between the altered V1 loop and T-cell line-tropic V3 loop that results in infection of Jurkat cells and peripheral blood lymphocytes.
Carrillo
A
A
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Ratner
L
L
D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D015686:Gene Products, env / Q000235:genetics; D015699:HIV Envelope Protein gp120 / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008561:Membrane Fusion; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D013601:T-Lymphocytes / Q000821:virology*; D014407:Tumor Cells, Cultured; D014616:Vaccinia virus; D001616:beta-Galactosidase / Q000235:genetics
D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; C059761:HIV envelope protein gp120 (135-148); C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D001616:beta-Galactosidase