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Dissecting HIV Virulence: Heritability of Setpoint Viral Load, CD4+ T Cell Decline and Per-Parasite Pathogenicity.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Bertels Frederic, Marzel Alex, Leventhal Gabriel, Mitov Venelin, Fellay Jacques, Günthard Huldrych F, Böni Jürg, Yerly Sabine, Klimkait Thomas, Aubert Vincent, Battegay Manuel, Rauch Andri, Cavassini Matthias, Calmy Alexandra, Bernasconi Enos, Schmid Patrick, Scherrer Alexandra U, Müller Viktor, Bonhoeffer Sebastian, Kouyos Roger, Regoes Roland R, Swiss HIV Cohort Study,
Project Swiss HIV Cohort Study (SHCS)
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Original article (peer-reviewed)

Journal Molecular biology and evolution
Page(s) 1 - 1
Title of proceedings Molecular biology and evolution
DOI 10.1093/molbev/msx246

Open Access

Type of Open Access Publisher (Gold Open Access)


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 genetype affects virulence mainly by modulating the per-parasite pathogenicity, while the indirect effect via the set-point viral load is minor.