Effect of amino acid changes in the V1/V2 region of the human immunodeficiency virus type 1 gp120 glycoprotein on subunit association, syncytium formation, and recognition by a neutralizing antibody.
The contributions of the first and second variable regions of the human immunodeficiency virus type 1 gp120 glycoprotein to envelope glycoprotein structure, function, and recognition by a neutralizing antibody were studied. Several mutants with substitutions in the V2 loop demonstrated complete dissociation of the gp120 and gp41 glycoproteins, suggesting that inappropriate changes in V2 conformation can affect subunit assembly. Some glycoproteins with changes in V1 or V2 were efficiently expressed on the cell surface and were able to bind CD4 but were deficient in syncytium formation and/or virus entry. Recognition of gp120 by the neutralizing monoclonal antibody G3-4 was affected by particular substitutions affecting residues 176 to 184 in the V2 loop. These results suggest that the V1/V2 variable regions of the human immunodeficiency virus type 1 gp120 glycoprotein play a role in postreceptor binding events in the membrane fusion process and can act as a target for neutralizing antibodies.
Division of Human Retrovirology, Dana-Farber Cancer Institute, New York, New York.
N
N
Sullivan
M
M
Thali
C
C
Furman
D D
DD
Ho
J
J
Sodroski
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000235:genetics; D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D002459:Cell Fusion; D002478:Cells, Cultured; D015483:HIV Antibodies / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009500:Neutralization Tests; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000382:microbiology; D014162:Transfection
D000596:Amino Acids; D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D008565:Membrane Proteins