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dc.contributor.author
Bertels, Frederic
dc.contributor.author
Marzel, Alex
dc.contributor.author
Leventhal, Gabriel
dc.contributor.author
Mitov, Venelin
dc.contributor.author
Fellay, Jacques
dc.contributor.author
Günthard, Huldrych F.
dc.contributor.author
Böni, Jürg
dc.contributor.author
Yerly, Sabine
dc.contributor.author
Klimkait, Thomas
dc.contributor.author
Aubert, Vincent
dc.contributor.author
Battegay, Manuel
dc.contributor.author
Rauch, Andri
dc.contributor.author
Cavassini, Matthias
dc.contributor.author
Calmy, Alexandra
dc.contributor.author
Bernasconi, Enos
dc.contributor.author
Schmid, Patrick
dc.contributor.author
Scherrer, Alexandra U.
dc.contributor.author
Müller, Viktor
dc.contributor.author
Bonhoeffer, Sebastian
dc.contributor.author
Kouyos, Roger
dc.contributor.author
Regoes, Roland R.
dc.date.accessioned
2018-04-25T12:27:31Z
dc.date.available
2018-01-16T15:16:56Z
dc.date.available
2018-01-18T15:43:27Z
dc.date.available
2018-04-20T11:22:30Z
dc.date.available
2018-04-25T12:27:31Z
dc.date.issued
2018-01
dc.identifier.issn
0737-4038
dc.identifier.issn
1537-1719
dc.identifier.other
10.1093/molbev/msx246
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/229655
dc.identifier.doi
10.3929/ethz-b-000229655
dc.description.abstract
Pathogen strains may differ in virulence because they attain different loads in their hosts, or because they induce different disease-causing mechanisms independent of their load. In evolutionary ecology, the latter is referred to as “per-parasite pathogenicity”. Using viral load and CD4+ T-cell measures from 2014 HIV-1 subtype B-infected individuals enrolled in the Swiss HIV Cohort Study, we investigated if virulence—measured as the rate of decline of CD4+ T cells—and per-parasite pathogenicity are heritable from donor to recipient. We estimated heritability by donor–recipient regressions applied to 196 previously identified transmission pairs, and by phylogenetic mixed models applied to a phylogenetic tree inferred from HIV pol sequences. Regressing the CD4+ T-cell declines and per-parasite pathogenicities of the transmission pairs did not yield heritability estimates significantly different from zero. With the phylogenetic mixed model, however, our best estimate for the heritability of the CD4+ T-cell decline is 17% (5–30%), and that of the per-parasite pathogenicity is 17% (4–29%). Further, we confirm that the set-point viral load is heritable, and estimate a heritability of 29% (12–46%). Interestingly, the pattern of evolution of all these traits differs significantly from neutrality, and is most consistent with stabilizing selection for the set-point viral load, and with directional selection for the CD4+ T-cell decline and the per-parasite pathogenicity. Our analysis shows that the viral genotype affects virulence mainly by modulating the per-parasite pathogenicity, while the indirect effect via the set-point viral load is minor.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Oxford University Press
en_US
dc.rights.uri
http://creativecommons.org/licenses/by-nc/4.0/
dc.subject
evolution of virulence
en_US
dc.subject
disease tolerance
en_US
dc.subject
per-parasite pathogenicity
en_US
dc.subject
heritability
en_US
dc.subject
HIV
en_US
dc.title
Dissecting HIV Virulence: Heritability of Setpoint Viral Load, CD4+ T-Cell Decline, and Per-Parasite Pathogenicity
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution-NonCommercial 4.0 International
dc.date.published
2017-10-03
ethz.journal.title
Molecular Biology and Evolution
ethz.journal.volume
35
en_US
ethz.journal.issue
1
en_US
ethz.pages.start
27
en_US
ethz.pages.end
37
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Oxford
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02350 - Dep. Umweltsystemwissenschaften / Dep. of Environmental Systems Science::02720 - Institut für Integrative Biologie / Institute of Integrative Biology::03584 - Bonhoeffer, Sebastian / Bonhoeffer, Sebastian
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02060 - Dep. Biosysteme / Dep. of Biosystems Science and Eng.::09490 - Stadler, Tanja / Stadler, Tanja
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02060 - Dep. Biosysteme / Dep. of Biosystems Science and Eng.::09490 - Stadler, Tanja / Stadler, Tanja
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02350 - Dep. Umweltsystemwissenschaften / Dep. of Environmental Systems Science::02720 - Institut für Integrative Biologie / Institute of Integrative Biology::03584 - Bonhoeffer, Sebastian / Bonhoeffer, Sebastian
en_US
ethz.date.deposited
2018-01-16T15:16:56Z
ethz.source
BATCH
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2018-04-25T12:27:35Z
ethz.rosetta.lastUpdated
2019-02-02T16:52:47Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
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