Viral genetic variation accounts for a third of variability in HIV-1 set-point viral load in Europe
Author(s)
Type
Journal Article
Abstract
HIV-1 set-point viral load—the approximately stable value of viraemia in the first years of chronic infection—is a strong predictor of clinical outcome and is highly variable across infected individuals. To better understand HIV-1 pathogenesis and the evolution of the viral population, we must quantify the heritability of set-point viral load, which is the fraction of variation in this phenotype attributable to viral genetic variation. However, current estimates of heritability vary widely, from 6% to 59%. Here we used a dataset of 2,028 seroconverters infected between 1985 and 2013 from 5 European countries (Belgium, Switzerland, France, the Netherlands and the United Kingdom) and estimated the heritability of set-point viral load at 31% (CI 15%–43%). Specifically, heritability was measured using models of character evolution describing how viral load evolves on the phylogeny of whole-genome viral sequences. In contrast to previous studies, (i) we measured viral loads using standardized assays on a sample collected in a strict time window of 6 to 24 months after infection, from which the viral genome was also sequenced; (ii) we compared 2 models of character evolution, the classical “Brownian motion” model and another model (“Ornstein–Uhlenbeck”) that includes stabilising selection on viral load; (iii) we controlled for covariates, including age and sex, which may inflate estimates of heritability; and (iv) we developed a goodness of fit test based on the correlation of viral loads in cherries of the phylogenetic tree, showing that both models of character evolution fit the data well. An overall heritability of 31% (CI 15%–43%) is consistent with other studies based on regression of viral load in donor–recipient pairs. Thus, about a third of variation in HIV-1 virulence is attributable to viral genetic variation.
Date Issued
2017-06-12
Date Acceptance
2017-05-09
Citation
PLoS Biology, 2017, 15 (6)
ISSN
1544-9173
Publisher
Public Library of Science (PLoS)
Journal / Book Title
PLoS Biology
Volume
15
Issue
6
Copyright Statement
This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
License URL
Sponsor
Medical Research Council (MRC)
Commission of the European Communities
Grant Number
MR/K010174/1B
339251
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Biology
Life Sciences & Biomedicine - Other Topics
IMMUNODEFICIENCY-VIRUS TYPE-1
PROGNOSTIC MARKERS
RNA LEVELS
INFECTION
AFRICA
TRANSMISSION
VIRULENCE
PLASMA
SEROCONVERSION
HERITABILITY
Publication Status
Published
Article Number
e2001855