Abstract

The HIV-1 reservoir is the major hurdle to curing HIV-1. However, the impact of the viral genome on the HIV-1 reservoir, i.e. its heritability, remains unknown. We investigate the heritability of the HIV-1 reservoir size and its long-term decay by analyzing the distribution of those traits on viral phylogenies from both partial-pol and viral near full-length genome sequences. We use a unique nationwide cohort of 610 well-characterized HIV-1 subtype-B infected individuals on suppressive ART for a median of 5.4 years. We find that a moderate but significant fraction of the HIV-1 reservoir size 1.5 years after the initiation of ART is explained by genetic factors. At the same time, we find more tentative evidence for the heritability of the long-term HIV-1 reservoir decay. Our findings indicate that viral genetic factors contribute to the HIV-1 reservoir size and hence the infecting HIV-1 strain may affect individual patients’ hurdle towards a cure.

The HIV reservoir is a major hurdle for a cure of HIV, but the factors determining its size and dynamics remain unclear. Here the authors show in a large cohort of 610 HIV-1 infected individuals, who are on suppressive ART for a median of 5.4 years, that viral genetic factors contribute substantially to the HIV-1 reservoir size.

Details

Title
Heritability of the HIV-1 reservoir size and decay under long-term suppressive ART
Author
Wan Chenjie 1   VIAFID ORCID Logo  ; Bachmann, Nadine 2   VIAFID ORCID Logo  ; Mitov Venelin 3   VIAFID ORCID Logo  ; Blanquart François 4 ; Céspedes, Susana Posada 5   VIAFID ORCID Logo  ; Turk Teja 2   VIAFID ORCID Logo  ; Neumann Kathrin 2   VIAFID ORCID Logo  ; Beerenwinkel Niko 6   VIAFID ORCID Logo  ; Bogojeska Jasmina 7 ; Fellay Jacques 8   VIAFID ORCID Logo  ; Roth, Volker 9   VIAFID ORCID Logo  ; Böni Jürg 10   VIAFID ORCID Logo  ; Perreau Matthieu 11 ; Klimkait, Thomas 12   VIAFID ORCID Logo  ; Yerly Sabine 13   VIAFID ORCID Logo  ; Battegay Manuel 14 ; Walti, Laura 15 ; Calmy Alexandra 16 ; Vernazza Pietro 17 ; Bernasconi Enos 18   VIAFID ORCID Logo  ; Cavassini Matthias 19 ; Metzner, Karin J 2   VIAFID ORCID Logo  ; Günthard, Huldrych F 2   VIAFID ORCID Logo  ; Kouyos, Roger D 2   VIAFID ORCID Logo  ; Anagnostopoulos Alexia 20 ; Böni Jürg 21 ; Braun, Dominique L 20 ; Bucher, Heiner C 22 ; Ciuffi, Angela 23 ; Dollenmaier Günter 24 ; Egger, Matthias 25 ; Elzi Luigia 11 ; Fehr, Jan 20 ; Furrer Hansjakob 12 ; Fux, Christoph A 26 ; Günthard Huldrych F 1 ; Haerry, David 27 ; Hasse, Barbara 20 ; Hirsch, Hans H 28 ; Hoffmann, Matthias 14 ; Hösli Irene 29 ; Huber, Michael 21 ; Kahlert, Christian 30 ; Kaiser, Laurent 9 ; Keiser, Olivia 25 ; Kovari Helen 20 ; Ledergerber Bruno 20 ; Martinetti Gladys 31 ; de Tejada Begona Martinez 32 ; Marzolini Catia 11 ; Müller Nicolas 20 ; Nicca Dunja 13 ; Paioni Paolo 33 ; Pantaleo Guiseppe 34 ; Rauch Andri 13 ; Rudin Christoph 35 ; Scherrer, Alexandra U 1 ; Schmid, Patrick 13 ; Speck, Roberto 20 ; Stöckle Marcel 11 ; Tarr, Philip 36 ; Trkola Alexandra 21 ; Wandeler Gilles 12 ; Weber, Rainer 20 

1  University Hospital Zurich, Department of Infectious Diseases and Hospital Epidemiology, Zurich, Switzerland (GRID:grid.412004.3) (ISNI:0000 0004 0478 9977); ETH Zurich, Department of Environmental Systems Science, Zurich, Switzerland (GRID:grid.5801.c) (ISNI:0000 0001 2156 2780) 
2  University Hospital Zurich, Department of Infectious Diseases and Hospital Epidemiology, Zurich, Switzerland (GRID:grid.412004.3) (ISNI:0000 0004 0478 9977); University of Zurich, Institute of Medical Virology, Zurich, Switzerland (GRID:grid.7400.3) (ISNI:0000 0004 1937 0650) 
3  ETH Zurich, Department of Biosystems Science and Engineering, Zurich, Switzerland (GRID:grid.5801.c) (ISNI:0000 0001 2156 2780); Swiss Institute of Bioinformatics, Lausanne, Switzerland (GRID:grid.419765.8) (ISNI:0000 0001 2223 3006) 
4  Collège de France, Center for Interdisciplinary Research in Biology, Paris, France (GRID:grid.410533.0) (ISNI:0000 0001 2179 2236) 
5  Swiss Institute of Bioinformatics, Lausanne, Switzerland (GRID:grid.419765.8) (ISNI:0000 0001 2223 3006); Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland (GRID:grid.5801.c) (ISNI:0000 0001 2156 2780) 
6  Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland (GRID:grid.5801.c) (ISNI:0000 0001 2156 2780) 
7  IBM Research - Zurich, Zurich, Switzerland (GRID:grid.410387.9) 
8  EPFL, School of Life Sciences, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049); Lausanne University Hospital and University of Lausanne, Precision Medicine Unit, Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662) 
9  University of Basel, Department of Mathematics and Computer Science, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642) 
10  University of Zurich, Institute of Medical Virology, Zurich, Switzerland (GRID:grid.7400.3) (ISNI:0000 0004 1937 0650) 
11  University of Lausanne, Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland (GRID:grid.9851.5) (ISNI:0000 0001 2165 4204) 
12  University of Basel, Molecular Virology, Department Biomedicine - Petersplatz, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642) 
13  Geneva University Hospital, Laboratory of Virology, Geneva, Switzerland (GRID:grid.150338.c) (ISNI:0000 0001 0721 9812) 
14  University of Basel, Department of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642) 
15  University of Bern, Department of Infectious Diseases, Inselspital, Bern University Hospital, Bern, Switzerland (GRID:grid.5734.5) (ISNI:0000 0001 0726 5157) 
16  University of Geneva, Institute of Global Health, Geneva, Switzerland (GRID:grid.8591.5) (ISNI:0000 0001 2322 4988) 
17  Cantonal Hospital of St. Gallen, Division of Infectious Diseases and Hospital Epidemiology, St. Gallen, Switzerland (GRID:grid.413349.8) (ISNI:0000 0001 2294 4705) 
18  Regional Hospital, Infectious Diseases Service, Lugano, Switzerland (GRID:grid.413349.8) 
19  University of Lausanne, Division of Infectious Diseases, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland (GRID:grid.9851.5) (ISNI:0000 0001 2165 4204) 
20  University Hospital Zurich, Department of Infectious Diseases and Hospital Epidemiology, Zurich, Switzerland (GRID:grid.412004.3) (ISNI:0000 0004 0478 9977) 
21  ETH Zurich, Department of Environmental Systems Science, Zurich, Switzerland (GRID:grid.5801.c) (ISNI:0000 0001 2156 2780) 
22  University of Basel, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642) 
23  University of Lausanne, Institute of Microbiology, University Hospital Lausanne, Lausanne, Switzerland (GRID:grid.9851.5) (ISNI:0000 0001 2165 4204) 
24  Canton St. Gallen, Centre for Laboratory Medicine, St. Gallen, Switzerland (GRID:grid.9851.5) 
25  University of Bern, Institute of Social and Preventive Medicine, Bern, Switzerland (GRID:grid.5734.5) (ISNI:0000 0001 0726 5157) 
26  Kantonsspital Aarau, Clinic for Infectious Diseases and Hospital Hygiene, Aarau, Switzerland (GRID:grid.413357.7) (ISNI:0000 0000 8704 3732) 
27  Positive Council, Zurich, Switzerland (GRID:grid.5801.c) 
28  Lausanne University Hospital and University of Lausanne, Precision Medicine Unit, Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662); University of Lausanne, Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland (GRID:grid.9851.5) (ISNI:0000 0001 2165 4204) 
29  University of Basel, Clinic for Obstetrics, University Hospital Basel, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642) 
30  Geneva University Hospital, Laboratory of Virology, Geneva, Switzerland (GRID:grid.150338.c) (ISNI:0000 0001 0721 9812); Children’s Hospital of Eastern Switzerland, St. Gallen, Switzerland (GRID:grid.414079.f) (ISNI:0000 0004 0568 6320) 
31  Cantonal Institute of Microbiology, Bellinzona, Switzerland (GRID:grid.412004.3) 
32  University of Geneva, Department of Obstetrics and Gynecology, University Hospital Geneva, Geneva, Switzerland (GRID:grid.8591.5) (ISNI:0000 0001 2322 4988) 
33  University of Zurich, University Children’s Hospital, Zurich, Switzerland (GRID:grid.7400.3) (ISNI:0000 0004 1937 0650) 
34  EPFL, School of Life Sciences, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049) 
35  University of Basel, University Children’s Hospital, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642) 
36  University of Basel, Kantonsspital Baselland, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-020-19198-7
ProQuest document ID
2471529875
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.