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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Unique mutational patterns in the envelope α2 amphipathic helix and acquisition of length in gp120 hypervariable domains are associated with resistance to autologous neutralization of subtype C human immunodeficiency virus type 1
Journal of Virology, Volume 81, No. 11, Year 2007
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Description
Autologous neutralizing antibodies (NAb) against human immunodeficiency virus type 1 generate viral escape variants; however, the mechanisms of escape are not clearly defined. In a previous study, we determined the susceptibilities of 48 donor and 25 recipient envelope (Env) glycoproteins from five subtype C heterosexual transmission pairs to NAb in donor plasma by using a virus pseudotyping assay, thereby providing an ideal setting to probe the determinants of susceptibility to neutralization. In the present study, acquisition of length in the Env gp120 hypervariable domains was shown to correlate with resistance to NAb in donor plasma (P = 0.01; Kendall's tau test) but not in heterologous plasma. Sequence divergence in the gp120 V1-to-V4 region also correlated with resistance to donor (P = 0.0002) and heterologous (P = 0.001) NAb. A mutual information analysis suggested possible associations of nine amino acid positions in V1 to V4 with NAb resistance to the donor's antibodies, and five of these were located within an 18-residue amphipathic helix (α2) located on the gp120 outer domain. High nonsynonymous-to-synonymous substitution (dN/dS) ratios, indicative of positive selection, were also found at these five positions in subtype C sequences in the database. Nevertheless, exchange of the entire α2 helix between resistant donor Envs and sensitive recipient Envs did not alter the NAb phenotype. The combined mutual information and dN/dS analyses suggest that unique mutational patterns in α2 and insertions in the V1-to-V4 region are associated with NAb resistance during subtype C infection but that the selected positions within the α2 helix must be linked to still other changes in Env to confer antibody escape. These findings suggest that subtype C viruses utilize mutations in the α2 helix for efficient viral replication and immune avoidance. Copyright © 2007, American Society for Microbiology. All Rights Reserved.
Authors & Co-Authors
Rong, Rong
United States, Atlanta
Emory University
Gnanakaran, Sandrasegaram
United States, Los Alamos
Los Alamos National Laboratory
Decker, Julie M.
United States, Birmingham
The University of Alabama at Birmingham
Bibollet-Ruche, Frédéric
United States, Birmingham
The University of Alabama at Birmingham
Taylor, Jesse Earl
United States, Los Alamos
Los Alamos National Laboratory
United States, La Jolla
La Jolla Institute for Immunology
Sfakianos, Jeffrey N.
United States, New Haven
Yale University
Mokili, John L.K.
United States, Los Alamos
Los Alamos National Laboratory
United Kingdom, Oxford
University of Oxford
Muldoon, Mark
United Kingdom, Manchester
The University of Manchester
Mulenga, Joseph
Zambia, Lusaka
Zambia Blood Transfusion Service
Allen, Susan A.
United States, Atlanta
Emory University
Hahn, Beatrice H.
United States, Birmingham
The University of Alabama at Birmingham
Shaw, George M.
United States, Birmingham
The University of Alabama at Birmingham
Blackwell, Jerry L.
United States, Atlanta
Emory University
Korber, Bette T.
United States, Los Alamos
Los Alamos National Laboratory
United States, Santa fe
Santa fe Institute
Hunter, Eric
United States, Atlanta
Emory University
Derdeyn, Cynthia A.
United States, Atlanta
Emory University
Statistics
Citations: 98
Authors: 16
Affiliations: 9
Identifiers
Doi:
10.1128/JVI.00257-07
ISSN:
0022538X