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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
The B cell response is redundant and highly focused on V1V2 during early subtype C infection in a Zambian seroconverter
Journal of Virology, Volume 85, No. 2, Year 2011
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Description
High-titer autologous neutralizing antibody responses have been demonstrated during early subtype C human immunodeficiency virus type 1 (HIV-1) infection. However, characterization of this response against autologous virus at the monoclonal antibody (MAb) level has only recently begun to be elucidated. Here we describe five monoclonal antibodies derived from a subtype C-infected seroconverter and their neutralizing activities against pseudoviruses that carry envelope glycoproteins from 48 days (0 month), 2 months, and 8 months after the estimated time of infection. Sequence analysis indicated that the MAbs arose from three distinct B cell clones, and their pattern of neutralization compared to that in patient plasma suggested that they circulated between 2 and 8 months after infection. Neutralization by MAbs representative of each B cell clone was mapped to two residues: position 134 in V1 and position 189 in V2. Mutational analysis revealed cooperative effects between glycans and residues at these two positions, arguing that they contribute to a single epitope. Analysis of the cognate gp120 sequence through homology modeling places this potential epitope near the interface between the V1 and V2 loops. Additionally, the escape mutation R189S in V2, which conferred resistance against all three MAbs, had no detrimental effect on virus replication in vitro. Taken together, our data demonstrate that independent B cells repeatedly targeted a single structure in V1V2 during early infection. Despite this assault, a single amino acid change was sufficient to confer complete escape with minimal impact on replication fitness. Copyright © 2011, American Society for Microbiology. All Rights Reserved.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3020014/bin/supp_85_2_905__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC3020014/bin/supp_85_2_905__1.pdf
Authors & Co-Authors
Lynch, Rebecca M.
United States, Atlanta
Emory University
Rong, Rong
United States, Atlanta
Emory University
Boliar, Saikat
United States, Atlanta
Emory University
Sethi, Anurag
United States, Los Alamos
Los Alamos National Laboratory Theoretical Division
Li, Bing
United States, Atlanta
Emory University
Mulenga, Joseph
Zambia, Lusaka
Zambia Blood Transfusion Service
Allen, Susan A.
United States, Atlanta
Emory University
United States, Atlanta
Rollins School of Public Health
Robinson, James E.
United States, New Orleans
Tulane University School of Medicine
Gnanakaran, Sandrasegaram
United States, Los Alamos
Los Alamos National Laboratory Theoretical Division
Derdeyn, Cynthia A.
United States, Atlanta
Emory University
Statistics
Citations: 70
Authors: 10
Affiliations: 5
Identifiers
Doi:
10.1128/JVI.02006-10
ISSN:
0022538X
e-ISSN:
10985514
Research Areas
Cancer
Health System And Policy
Infectious Diseases
Violence And Injury