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2017-06-12Zeitschriftenartikel DOI: 10.1371/journal.pbio.2001855
Viral genetic variation accounts for a third of variability in HIV-1 set-point viral load in Europe
dc.contributor.authorBlanquart, François
dc.contributor.authorWymant, Chris
dc.contributor.authorCornelissen, Marion
dc.contributor.authorGall, Astrid
dc.contributor.authorBakker, Margreet
dc.contributor.authorBezemer, Daniela
dc.contributor.authorHall, Matthew
dc.contributor.authorHillebregt, Mariska
dc.contributor.authorOng, Swee Hoe
dc.contributor.authorAlbert, Jan
dc.contributor.authorBannert, Norbert
dc.contributor.authorFellay, Jacques
dc.contributor.authorFransen, Katrien
dc.contributor.authorGourlay, Annabelle J.
dc.contributor.authorGrabowski, M. Kate
dc.contributor.authorGunsenheimer-Bartmeyer, Barbara
dc.contributor.authorGünthard, Huldrych F.
dc.contributor.authorKivelä, Pia
dc.contributor.authorKouyos, Roger
dc.contributor.authorLaeyendecker, Oliver
dc.contributor.authorLiitsola, Kirsi
dc.contributor.authorMeyer, Laurence
dc.contributor.authorPorter, Kholoud
dc.contributor.authorRistola, Matti
dc.contributor.authorSighem, Ard van
dc.date.accessioned2018-05-07T20:01:51Z
dc.date.available2018-05-07T20:01:51Z
dc.date.created2017-06-13
dc.date.issued2017-06-12none
dc.identifier.otherhttp://edoc.rki.de/oa/articles/reGY3KSnynuyI/PDF/22YVnD7I99aKA.pdf
dc.identifier.urihttp://edoc.rki.de/176904/2643
dc.description.abstractHIV-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.eng
dc.language.isoeng
dc.publisherRobert Koch-Institut, Infektionskrankheiten / Erreger
dc.subject.ddc610 Medizin
dc.titleViral genetic variation accounts for a third of variability in HIV-1 set-point viral load in Europe
dc.typeperiodicalPart
dc.identifier.urnurn:nbn:de:0257-10052691
dc.identifier.doi10.1371/journal.pbio.2001855
dc.identifier.doihttp://dx.doi.org/10.25646/2568
local.edoc.container-titlePLoS Biology
local.edoc.fp-subtypeArtikel
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttps://doi.org/10.1371/journal.pbio.2001855
local.edoc.container-year2017

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