Immune escape by human immunodeficiency virus type 1 from neutralizing antibodies: evidence for multiple pathways.
Sera from many HIV-1-infected individuals contain broadly reactive, specific neutralizing antibodies. Despite their broad reactivity, variant viruses, resistant to neutralization, can be selected in vitro in the presence of such antisera. We have previously shown that neutralization resistance of an escape mutant with an amino acid substitution in the transmembrane protein (A582T) occurs because of alteration of a conformational epitope that is recognized by neutralizing antibodies directed against the CD4 binding site. In this report we demonstrate that immune escape via a single-amino-acid substitution (A281V) within a conserved region of the envelope glycoprotein gp120 confers neutralization resistance against a broadly reactive neutralizing antiserum from a seropositive individual. We show this alteration affects V3 and additional regions unrelated to V3 or the CD4 binding site. Together with previous studies on escape mutants selected in vitro, our findings suggest that immune-selective pressure can arise by multiple pathways.
Watkins
B A
BA
Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland 20892.
Reitz
M S
MS
Wilson
C A
CA
Aldrich
K
K
Davis
A E
AE
Robert-Guroff
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology; D002478:Cells, Cultured; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D006679:HIV Seropositivity / Q000097:blood* / Q000235:genetics; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000276:immunology*; D009500:Neutralization Tests; D011487:Protein Conformation; D012641:Selection, Genetic
D000914:Antibodies, Viral; D015704:CD4 Antigens; D000939:Epitopes; D015699:HIV Envelope Protein gp120