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PMID: 11356967 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Antigenic variation within the CD4 binding site of human immunodeficiency virus type 1 gp120: effects on chemokine receptor utilization.

Journal of virology ·Vol. 75 ·No. 12 ·2001-06-00 ·Pages 5593-603

Hammond AL, Lewis J, May J, Albert J, Balfe P, McKeating JA

Abstract

To assess the antigenicity of envelope glycoproteins derived from primary human immunodeficiency virus type 1 populations, their interactions with the receptor CD4, and their coreceptor usage, we have cloned and expressed multiple gp120 proteins from a number of primary virus isolates. Characterization of these proteins showed a high degree of antigenic polymorphism both within the CD4 binding site and in defined neutralization epitopes, which may partially account for the general resistance of primary isolates to neutralizing agents. Furthermore, chimeric viruses expressing gp120 proteins with reduced CD4 binding abilities are viable, suggesting that primary viruses may require a less avid interaction with the receptor CD4 to initiate infection than do their laboratory-adapted counterparts. The coreceptor usage of chimeric viruses was related to the ability of the virus to bind CD4, with reduced CD4 binding correlating with preferential usage of CXCR4. Changes in coreceptor usage mapped to sequence changes in the C2 and V4 regions, with no changes seen in the V3 region.

MeSH Terms
Amino Acid Sequence Animals Antigenic Variation Binding Sites CD4 Antigens/metabolism HIV Envelope Protein gp120/chemistry,genetics,immunology,metabolism HIV Infections/virology HIV-1/immunology Humans Male Molecular Sequence Data Peptide Fragments/chemistry,genetics,metabolism Polymerase Chain Reaction Rats Receptors, Chemokine/metabolism Recombinant Fusion Proteins/metabolism Sequence Analysis, DNA
Chemicals
CD4 Antigens HIV Envelope Protein gp120 HIV envelope protein gp120 (305-321) Peptide Fragments Receptors, Chemokine Recombinant Fusion Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Hammond A L
School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading RG6 2AJ, United Kingdom. murphy.anthea@mayo.edu
Lewis J
May J
Albert J
Balfe P
McKeating J A
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.75.12.5593-5603.2001
Email
murphy.anthea@mayo.edu
Published
2001-06-00
Pages
5593-603
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC114272
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.75.12.5593-5603.2001 PMC Full Text View journal details
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