Virus-induced target cell activation reconciles set-point viral load heritability and within-host evolution
Open access
Datum
2013-12Typ
- Journal Article
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. Mehr anzeigen
Persistenter Link
https://doi.org/10.3929/ethz-b-000073580Publikationsstatus
publishedExterne Links
Zeitschrift / Serie
EpidemicsBand
Seiten / Artikelnummer
Verlag
ElsevierThema
Set-point viral load; Virus-induced target cell activation; Within-host evolution; Between-host evolution; Viral load heritabilityOrganisationseinheit
03584 - Bonhoeffer, Sebastian / Bonhoeffer, Sebastian
Förderung
268540 - The population biology of drug resistance: Key principles for a more sustainable use of drugs (EC)
133129 - Evolutionary genetics of HIV-1: Exploring evolution on complex fitness landscapes (SNF)
Zugehörige Publikationen und Daten
Is referenced by: https://doi.org/10.3929/ethz-b-000087130