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PMID: 15507649 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Evolutionary dynamics of the glycan shield of the human immunodeficiency virus envelope during natural infection and implications for exposure of the 2G12 epitope.

Journal of virology ·Vol. 78 ·No. 22 ·2004-11-00 ·Pages 12625-37

Dacheux L, Moreau A, Ataman-Onal Y, Biron F, Verrier B, Barin F

Abstract

Elucidation of the kinetics of exposure of neutralizing epitopes on the envelope of human immunodeficiency virus type 1 (HIV-1) during the course of infection may provide key information about how HIV escapes the immune system or why its envelope is such a poor immunogen to induce broadly efficient neutralizing antibodies. We analyzed the kinetics of exposure of the epitopes corresponding to the broadly neutralizing human monoclonal antibodies immunoglobulin G1b12 (IgG1b12), 2G12, and 2F5 at the quasispecies level during infection. We studied the antigenicity and sequences of 94 full-length envelope clones present during primary infection and at least 4 years later in four HIV-1 clade B-infected patients. No or only minor exposure differences were observed for the 2F5 and IgG1b12 epitopes between the early and late clones. Conversely, the envelope glycoproteins of the HIV-1 quasispecies present during primary infection did not expose the 2G12 neutralizing epitope, unlike those present after several years in three of the four patients. Sequence analysis revealed major differences at potential N-linked glycosylation sites between early and late clones, particularly at positions known to be important for 2G12 binding. Our study, in natural mutants, confirms that the glycosylation sites N295, N332, and N392 are essential for 2G12 binding. This study demonstrates the relationship between the evolving "glycan shield " of HIV and the kinetics of exposure of the 2G12 epitope during the course of natural infection.

MeSH Terms
Amino Acid Sequence Antibodies, Monoclonal/immunology CD4 Antigens/metabolism Epitopes Evolution, Molecular Gene Products, env/chemistry,immunology,metabolism Glycosylation HIV Antibodies/immunology HIV-1/immunology Humans Male Molecular Sequence Data Phylogeny Polysaccharides/immunology
Chemicals
Antibodies, Monoclonal CD4 Antigens Epitopes Gene Products, env HIV Antibodies Polysaccharides
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Dacheux Laurent
Laboratoire de Virologie, CHU Bretonneau, 37044 Tours cedex, France.
Moreau Alain
Ataman-Onal Yasemin
Biron François
Verrier Bernard
Barin Francis
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.78.22.12625-12637.2004
Published
2004-11-00
Pages
12625-37
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC525068
Subset
IM
Databases
GENBANK
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External Links
PubMed source DOI: 10.1128/JVI.78.22.12625-12637.2004 PMC Full Text View journal details
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