Article (Scientific journals)
HLA-driven convergence of HIV-1 viral subtypes B and F toward the adaptation to immune responses in human populations.
Dilernia, Dario Alberto; Jones, Leandro; Rodriguez, Sabrina et al.
2008In PLoS ONE, 3 (10), p. 3429
Peer Reviewed verified by ORBi
 

Files


Full Text
pone.0003429.s002.pdf
Publisher postprint (798.04 kB)
Download
Annexes
pone.0003429.s001.pdf
Publisher postprint (971.08 kB)
Download
pone.0003429.s002.pdf
Publisher postprint (798.04 kB)
Download
pone.0003429.s003.pdf
Publisher postprint (2.53 MB)
Download
pone.0003429.s004.pdf
Publisher postprint (1.27 MB)
Download
pone.0003429.s005.pdf
Publisher postprint (1.05 MB)
Download
pone.0003429.s006.pdf
Publisher postprint (1.09 MB)
Download

All documents in ORBi are protected by a user license.

Send to



Details



Keywords :
Antigens, Viral/genetics; Biological Evolution; Epitopes/genetics; Gene Products, gag/genetics/immunology; HIV-1/genetics/immunology; HLA Antigens/immunology; HLA-B Antigens/immunology; Humans; Immunity; Models, Statistical; Mutation; Selection, Genetic; T-Lymphocytes, Cytotoxic/immunology
Abstract :
[en] BACKGROUND: Cytotoxic T-Lymphocyte (CTL) response drives the evolution of HIV-1 at a host-level by selecting HLA-restricted escape mutations. Dissecting the dynamics of these escape mutations at a population-level would help to understand how HLA-mediated selection drives the evolution of HIV-1. METHODOLOGY/PRINCIPAL FINDINGS: We undertook a study of the dynamics of HIV-1 CTL-escape mutations by analyzing through statistical approaches and phylogenetic methods the viral gene gag sequenced in plasma samples collected between the years 1987 and 2006 from 302 drug-naive HIV-positive patients. By applying logistic regression models and after performing correction for multiple test, we identified 22 potential CTL-escape mutations (p-value<0.05; q-value<0.2); 10 of these associations were confirmed in samples biologically independent by a Bayesian Markov Chain Monte-Carlo method. Analyzing their prevalence back in time we found that escape mutations that are the consensus residue in samples collected after 2003 have actually significantly increased in time in one of either B or F subtype until becoming the most frequent residue, while dominating the other viral subtype. Their estimated prevalence in the viral subtype they did not dominate was lower than 30% for the majority of samples collected at the end of the 80's. In addition, when screening the entire viral region, we found that the 75% of positions significantly changing in time (p<0.05) were located within known CTL epitopes. CONCLUSIONS: Across HIV Gag protein, the rise of polymorphisms from independent origin during the last twenty years of epidemic in our setting was related to an association with an HLA allele. The fact that these mutations accumulated in one of either B or F subtypes have also dominated the other subtype shows how this selection might be causing a convergence of viral subtypes to variants which are more likely to evade the immune response of the population where they circulate.
Disciplines :
Immunology & infectious disease
Author, co-author :
Dilernia, Dario Alberto
Jones, Leandro
Rodriguez, Sabrina ;  National Institute of Agriculture Technology INTA-Castelar, Argentina > CNIA > Institute of Virology
Turk, Gabriela
Rubio, Andrea E.
Pampuro, Sandra
Gomez-Carrillo, Manuel
Bautista, Christian T.
Deluchi, Gabriel
Benetucci, Jorge
Lasala, Maria Beatriz
Lourtau, Leonardo
Losso, Marcelo Horacio
Perez, Hector
Cahn, Pedro
Salomon, Horacio
More authors (6 more) Less
Language :
English
Title :
HLA-driven convergence of HIV-1 viral subtypes B and F toward the adaptation to immune responses in human populations.
Publication date :
21 October 2008
Journal title :
PLoS ONE
eISSN :
1932-6203
Publisher :
Public Library of Science, United States - California
Volume :
3
Issue :
10
Pages :
e3429
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 23 January 2013

Statistics


Number of views
129 (3 by ULiège)
Number of downloads
139 (0 by ULiège)

Scopus citations®
 
18
Scopus citations®
without self-citations
11
OpenCitations
 
19

Bibliography


Similar publications



Contact ORBi