Effects of amino acid changes in the extracellular domain of the human immunodeficiency virus type 1 gp41 envelope glycoprotein.
Changes were introduced into conserved amino acids within the ectodomain of the human immunodeficiency virus type 1 (HIV-1) gp41 transmembrane envelope glycoprotein. The effect of these changes on the structure and function of the HIV-1 envelope glycoproteins was examined. The gp41 glycoprotein contains an amino-terminal fusion peptide (residues 512 to 527) and a disulfide loop near the middle of the extracellular domain (residues 598 to 604). Mutations affecting the hydrophobic sequences between these two regions resulted in two phenotypes. Some changes in amino acids 528 to 562 resulted in a loss of the noncovalent association between gp41 and the gp120 exterior glycoprotein. Amino acid changes in other parts of the gp41 glycoprotein (residues 608 and 628) also resulted in subunit dissociation. Some changes affecting amino acids 568 to 596 resulted in envelope glycoproteins partially or completely defective in mediating membrane fusion. Syncytium formation was more sensitive than virus entry to these changes. Changes in several amino acids from 647 to 675 resulted in higher-than-wild-type syncytium-forming ability. One of these amino acid changes affecting tryptophan 666 resulted in escape from neutralization by an anti-gp41 human monoclonal antibody, 2F5. These results contribute to an understanding of the functional regions of the HIV-1 gp41 ectodomain.
Cao
J
J
Division of Human Retrovirology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Bergeron
L
L
Helseth
E
E
Thali
M
M
Repke
H
H
Sodroski
J
J
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics*; D000596:Amino Acids / Q000235:genetics; D015704:CD4 Antigens / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics*; D008561:Membrane Fusion; D016297:Mutagenesis, Site-Directed; D009500:Neutralization Tests; D010641:Phenotype; D011499:Protein Processing, Post-Translational; D013329:Structure-Activity Relationship
D000596:Amino Acids; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41