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

Bertels F; Marzel A; Leventhal G; Mitov V; Fellay J; Günthard HF; Böni J; Yerly S; Klimkait T; Aubert V; Battegay M; Rauch A; Cavassini M; Calmy A; Bernasconi E; Schmid P; Scherrer AU; Müller V; Bonhoeffer S; Kouyos R; Regoes RR

doi:10.1093/molbev/msx246

Back

Journal article

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

Bertels F Institute of Integrative Biology, ETH Zurich, Zurich, Switzerland.
Marzel A Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
Leventhal G Institute of Integrative Biology, ETH Zurich, Zurich, Switzerland.
Mitov V Department of Biosystems Science and Engineering, ETH Zurich, Zurich, Switzerland.
Fellay J School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Günthard HF Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
Böni J Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
Yerly S Division of Infectious Diseases, Laboratory of Virology, Geneva University Hospital, Geneva, Switzerland.
Klimkait T Molecular Virology, Department of Biomedicine - Petersplatz, University of Basel, Basel, Switzerland.
Aubert V Division of Immunology and Allergy, University Hospital Lausanne, Lausanne, Switzerland.
Battegay M Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
Rauch A Department of Infectious Diseases, Berne University Hospital and University of Berne, Berne, Switzerland.
Cavassini M Division of Infectious Diseases, University Hospital Lausanne, Lausanne, Switzerland.
Calmy A HIV/AIDS Unit, Infectious Disease Service, Geneva University Hospital, Geneva, Switzerland.
Bernasconi E Division of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland.
Schmid P Division of Infectious Diseases, Cantonal Hospital St Gallen, St Gallen, Switzerland.
Scherrer AU Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
Müller V Institute of Biology, Eötvös Loránd University, Budapest, Hungary.
Bonhoeffer S Institute of Integrative Biology, ETH Zurich, Zurich, Switzerland.
Kouyos R Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
Regoes RR Institute of Integrative Biology, ETH Zurich, Zurich, Switzerland.

2017-10-14

Published in:

Molecular biology and evolution. - 2018

English 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.

Language