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Title: HIV evolution in early infection: selection pressures, patterns of insertion and deletion, and the impact of apobec

Abstract

The pattern of viral diversification in newly infected individuals provides information about the host environment and immune responses typically experienced by the newly transmitted virus. For example, sites that tend to evolve rapidly across multiple early-infection patients could be involved in enabling escape from common early immune responses, represent adaptation for rapid growth in a newly infected host, or reversion from less fit forms of the virus that were selected for immune escape in previous hosts. Here we investigated the diversification of HIV -I env coding sequences in 81 very early B SUbtype infections previously shown to have resulted from transmission or expansion of single viruses (n=78) or two closely related viruses (n=3). In these cases the sequence of the infecting virus can be estimated accurately, enabling inference of both the direction of substitutions as well as distinction between insertion and deletion events. By integrating information across multiple acutely infected hosts, we find evidence of adaptive evolution of HIV-1 envand identified a subset of codon sites that diversified more rapidly than can be explained by a model of neutral evolution. Of 24 such rapidly diversifying sites, 14 were either (i) clustered and embedded in CTL epitopes that were verified experimentallymore » or predicted based on the individual's HLA or (ii) in a nucleotide context indicative of APOBEC mediated G-to-A substitutions, despite having excluded heavily hypermutated sequences prior to the analysis. In several cases, a rapidly evolving site was both embedded in an APOBEC motif and in a CTL epitope, suggesting that APOBEC may facilitate early immune escape. Ten rapidly diversifying sites could not be explained by CTL escape or APOBEC hypermutation, including the most frequently mutated site, in the fusion peptide of gp4l. We also examined the distribution, extent, and sequence context of insertions and deletions and provide evidence that the length variation seen in hypervariable loop regions of the envelope glycoprotein is a consequence of selection and not mutational hotspots. These results provide a detailed view of the process of diversification of HIV-1 following transmission.« less

Authors:
 [1];  [1];  [1];  [1];  [1]
  1. Los Alamos National Laboratory
Publication Date:
Research Org.:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
956486
Report Number(s):
LA-UR-09-00145; LA-UR-09-145
TRN: US201013%%189
DOE Contract Number:  
AC52-06NA25396
Resource Type:
Journal Article
Journal Name:
PLoS Computational Biology
Additional Journal Information:
Journal Name: PLoS Computational Biology
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; AIDS VIRUS; CODONS; DISTRIBUTION; DIVERSIFICATION; GLYCOPROTEINS; NUCLEOTIDES; PATIENTS; PEPTIDES; VIRUSES

Citation Formats

Korber, Bette, Bhattacharya, Tanmoy, Giorgi, Elena, Gaschen, B, and Daniels, M. HIV evolution in early infection: selection pressures, patterns of insertion and deletion, and the impact of apobec. United States: N. p., 2009. Web.
Korber, Bette, Bhattacharya, Tanmoy, Giorgi, Elena, Gaschen, B, & Daniels, M. HIV evolution in early infection: selection pressures, patterns of insertion and deletion, and the impact of apobec. United States.
Korber, Bette, Bhattacharya, Tanmoy, Giorgi, Elena, Gaschen, B, and Daniels, M. 2009. "HIV evolution in early infection: selection pressures, patterns of insertion and deletion, and the impact of apobec". United States. https://www.osti.gov/servlets/purl/956486.
@article{osti_956486,
title = {HIV evolution in early infection: selection pressures, patterns of insertion and deletion, and the impact of apobec},
author = {Korber, Bette and Bhattacharya, Tanmoy and Giorgi, Elena and Gaschen, B and Daniels, M},
abstractNote = {The pattern of viral diversification in newly infected individuals provides information about the host environment and immune responses typically experienced by the newly transmitted virus. For example, sites that tend to evolve rapidly across multiple early-infection patients could be involved in enabling escape from common early immune responses, represent adaptation for rapid growth in a newly infected host, or reversion from less fit forms of the virus that were selected for immune escape in previous hosts. Here we investigated the diversification of HIV -I env coding sequences in 81 very early B SUbtype infections previously shown to have resulted from transmission or expansion of single viruses (n=78) or two closely related viruses (n=3). In these cases the sequence of the infecting virus can be estimated accurately, enabling inference of both the direction of substitutions as well as distinction between insertion and deletion events. By integrating information across multiple acutely infected hosts, we find evidence of adaptive evolution of HIV-1 envand identified a subset of codon sites that diversified more rapidly than can be explained by a model of neutral evolution. Of 24 such rapidly diversifying sites, 14 were either (i) clustered and embedded in CTL epitopes that were verified experimentally or predicted based on the individual's HLA or (ii) in a nucleotide context indicative of APOBEC mediated G-to-A substitutions, despite having excluded heavily hypermutated sequences prior to the analysis. In several cases, a rapidly evolving site was both embedded in an APOBEC motif and in a CTL epitope, suggesting that APOBEC may facilitate early immune escape. Ten rapidly diversifying sites could not be explained by CTL escape or APOBEC hypermutation, including the most frequently mutated site, in the fusion peptide of gp4l. We also examined the distribution, extent, and sequence context of insertions and deletions and provide evidence that the length variation seen in hypervariable loop regions of the envelope glycoprotein is a consequence of selection and not mutational hotspots. These results provide a detailed view of the process of diversification of HIV-1 following transmission.},
doi = {},
url = {https://www.osti.gov/biblio/956486}, journal = {PLoS Computational Biology},
number = ,
volume = ,
place = {United States},
year = {Thu Jan 01 00:00:00 EST 2009},
month = {Thu Jan 01 00:00:00 EST 2009}
}