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PMID: 7693973 Published · ppublish English Journal Article

Immune escape by human immunodeficiency virus type 1 from neutralizing antibodies: evidence for multiple pathways.

Journal of virology ·Vol. 67 ·No. 12 ·1993-12-00 ·Pages 7493-500

Watkins BA, Reitz MS, Wilson CA, Aldrich K, Davis AE, Robert-Guroff M

Abstract

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.

MeSH Terms
Amino Acid Sequence Animals Antibodies, Viral/blood,immunology CD4 Antigens/immunology Cells, Cultured Epitopes/genetics,immunology HIV Envelope Protein gp120/genetics,immunology HIV Seropositivity/blood,genetics HIV-1/genetics,immunology Humans Molecular Sequence Data Mutation/immunology Neutralization Tests Protein Conformation Selection, Genetic
Chemicals
Antibodies, Viral CD4 Antigens Epitopes HIV Envelope Protein gp120
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Watkins B A
Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland 20892.
Reitz M S
Wilson C A
Aldrich K
Davis A E
Robert-Guroff M
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.67.12.7493-7500.1993
Published
1993-12-00
Pages
7493-500
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC238215
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.67.12.7493-7500.1993 PMC Full Text View journal details
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