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dc.contributor.author
Hool, Anna
dc.contributor.author
Leventhal, Gabriel E.
dc.contributor.author
Bonhoeffer, Sebastian
dc.date.accessioned
2019-06-27T15:00:02Z
dc.date.available
2017-06-10T23:05:10Z
dc.date.available
2018-05-31T12:33:22Z
dc.date.available
2019-06-27T12:08:55Z
dc.date.available
2019-06-27T15:00:02Z
dc.date.issued
2013-12
dc.identifier.issn
1878-0067
dc.identifier.issn
1755-4365
dc.identifier.other
10.1016/j.epidem.2013.09.002
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/73580
dc.identifier.doi
10.3929/ethz-b-000073580
dc.description.abstract
The asymptomatic phase of HIV-1 infections is characterised by a stable set-point viral load (SPVL) within patients. The SPVL is a strong predictor of disease progression and shows considerable variation of multiple orders of magnitude between patients. Recent studies have found that the SPVL in donor and recipient pairs is strongly correlated indicating that the virus genotype strongly influences viral load. Viral genetic factors that increase both viral load and the replicative capacity of the virus would result in rapid within-host evolution to higher viral loads. Reconciling a stable SPVL over time with high SPVL heritability requires viral genetic factors that strongly influence SPVL but only weakly influence the competitive ability of the virus within hosts. We propose a virus trait that affects the activation of target cells, and therefore viral load, but does not confer a competitive advantage to the virus. We incorporate this virus-induced target cell activation into within- and between-host models and determine its effect on the competitive ability of virus strains and on the variation in SPVL in the host population. On the within-host level, our results show that higher rates of virus-induced target cell activation increase the SPVL and confer no selective advantage to the virus. This leads to a build up of diversity in target cell activation rates in the virus population during within-host evolution. On the between-host level, higher rates of target cell activation and therefore higher SPVL affect the transmission potential of the virus. Random selection of a new founder strain from the diverse virus population within a donor results in a standing variation in SPVL in the host population. Therefore, virus-induced target cell activation can explain the heritability of SPVL, the absence of evolution to higher viral loads during infection and a large standing variation in SPVL between hosts.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Elsevier
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/3.0/
dc.subject
Set-point viral load
en_US
dc.subject
Virus-induced target cell activation
en_US
dc.subject
Within-host evolution
en_US
dc.subject
Between-host evolution
en_US
dc.subject
Viral load heritability
en_US
dc.title
Virus-induced target cell activation reconciles set-point viral load heritability and within-host evolution
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 3.0 Unported
dc.date.published
2013-09-23
ethz.journal.title
Epidemics
ethz.journal.volume
5
en_US
ethz.journal.issue
4
en_US
ethz.pages.start
174
en_US
ethz.pages.end
180
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.grant
The population biology of drug resistance: Key principles for a more sustainable use of drugs
en_US
ethz.grant
Evolutionary genetics of HIV-1: Exploring evolution on complex fitness landscapes
en_US
ethz.identifier.scopus
ethz.publication.place
Amsterdam
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.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
ethz.grant.agreementno
268540
ethz.grant.agreementno
133129
ethz.grant.fundername
EC
ethz.grant.fundername
SNF
ethz.grant.funderDoi
10.13039/501100000780
ethz.grant.funderDoi
10.13039/501100001711
ethz.grant.program
FP7
ethz.grant.program
Bonus of Excellence
ethz.relation.isReferencedBy
10.3929/ethz-b-000087130
ethz.date.deposited
2017-06-10T23:08:10Z
ethz.source
ECIT
ethz.identifier.importid
imp5936511ea940693844
ethz.ecitpid
pub:116506
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-18T10:09:25Z
ethz.rosetta.lastUpdated
2019-06-27T15:00:25Z
ethz.rosetta.versionExported
true
ethz.COinS
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