Journal article
Africa-specific human genetic variation near CHD1L associates with HIV-1 load
Nature (London), Vol.620, pp.1025-1030
2023
PMID: 37532928
Abstract
HIV-1 remains a global health crisis1, highlighting the need to identify new targets for therapies. Here, given the disproportionate HIV-1 burden and marked human genome diversity in Africa2, we assessed the genetic determinants of control of set-point viral load in 3,879 people of African ancestries living with HIV-1 participating in the international collaboration for the genomics of HIV3. We identify a previously undescribed association signal on chromosome 1 where the peak variant associates with an approximately 0.3 log10-transformed copies per ml lower set-point viral load per minor allele copy and is specific to populations of African descent. The top associated variant is intergenic and lies between a long intergenic non-coding RNA (LINC00624) and the coding gene CHD1L, which encodes a helicase that is involved in DNA repair4. Infection assays in iPS cell-derived macrophages and other immortalized cell lines showed increased HIV-1 replication in CHD1L-knockdown and CHD1L-knockout cells. We provide evidence from population genetic studies that Africa-specific genetic variation near CHD1L associates with HIV replication in vivo. Although experimental studies suggest that CHD1L is able to limit HIV infection in some cell types in vitro, further investigation is required to understand the mechanisms underlying our observations, including any potential indirect effects of CHD1L on HIV spread in vivo that our cell-based assays cannot recapitulate.
Details
- Title
- Africa-specific human genetic variation near CHD1L associates with HIV-1 load
- Authors/Creators
- Paul J McLaren - University of ManitobaImmacolata Porreca - Wellcome Sanger InstituteGennaro Iaconis - University of CambridgeHoi Ping Mok - University of CambridgeSubhankar Mukhopadhyay - King's College LondonEmre Karakoc - Wellcome Sanger InstituteSara Cristinelli - University of LausanneCristina Pomilla - Wellcome Sanger InstituteIstván Bartha - SIB Swiss Institute of BioinformaticsChristian W Thorball - University of LausanneRiley H Tough - University of ManitobaPaolo Angelino - SIB Swiss Institute of BioinformaticsCher S Kiar - King's College LondonTommy Carstensen - University of CambridgeSegun Fatumo - Faculty (United Kingdom)Tarryn Porter - Wellcome Sanger InstituteIsobel Jarvis - University of CambridgeWilliam C Skarnes - Jackson LaboratoryAndrew Bassett - Wellcome Sanger InstituteMarianne K DeGorter - Stanford University School of MedicineMohana Prasad Sathya Moorthy - Stanford University School of MedicineJeffrey F Tuff - Sexually Transmitted and Blood-Borne Infections Division at JC Wilt Infectious Diseases Research Centre, National Microbiology Laboratory Branch, Public Health Agency of Canada, Winnipeg, Manitoba, CanadaEun-Young Kim - Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL, USAMiriam Walter - Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL, USALacy M Simons - Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL, USAArman Bashirova - Laboratoire d’immunologie intégrative du cancerSusan Buchbinder - San Francisco Department of Public HealthMary Carrington - Ragon Institute of MGH, MIT and HarvardAndrea Cossarizza - University of Modena and Reggio EmiliaAndrea De Luca - University of SienaJames J Goedert - National Institutes of HealthDavid B Goldstein - Columbia UniversityDavid W Haas - Vanderbilt University School of MedicineJoshua T Herbeck - University of Washington, SeattleEric O Johnson - RTI InternationalPontiano Kaleebu - London School of Hygiene and Tropical Medicine, London, UKWilliam Kilembe - Center for Family Health Research-Zambia, Lusaka, ZambiaGregory D Kirk - Johns Hopkins UniversityNeeltje A Kootstra - University of AmsterdamAlex H Kral - RTI InternationalOlivier Lambotte - Bicêtre HospitalMa Luo - Vaccine and Therapeutics Laboratory, Medical and Scientific Affairs, National Microbiology Laboratory Branch, Public Health Agency of Canada, Winnipeg, Manitoba, CanadaSimon Mallal - Institute for Immunology & Infectious Diseases, Murdoch University, Perth, Western Australia, AustraliaJavier Martinez-Picado - Instituto de Salud Carlos IIILaurence Meyer - AP-HP, Hôpital de Bicêtre, Département d'Épidémiologie, Le Kremlin Bicêtre, FranceJosé M Miro - Universitat de BarcelonaPravi Moodley - National Health Laboratory Service, South Africa and University of KwaZulu-Natal, Durban, South AfricaAyesha A Motala - Department of Diabetes and Endocrinology, School of Clinical Medicine, University of KwaZulu-Natal, Durban, South AfricaJames I Mullins - University of Washington, SeattleKireem Nam - Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL, USANiels Obel - Copenhagen University HospitalFraser Pirie - Department of Diabetes and Endocrinology, School of Clinical Medicine, University of KwaZulu-Natal, Durban, South AfricaFrancis A Plummer - University of ManitobaGuido Poli - Vita-Salute San Raffaele UniversityMatthew A Price - University of California, San FranciscoAndri Rauch - University of BernIoannis Theodorou - Laboratoire d'Immunologie, Hôpital Robert Debré Paris, Paris, FranceAlexandra Trkola - University of ZurichBruce D Walker - Howard Hughes Medical InstituteCheryl A Winkler - Frederick National Laboratory for Cancer ResearchJean-François Zagury - Conservatoire National des Arts et MétiersStephen B Montgomery - Stanford University School of MedicineAngela Ciuffi - University of LausanneJudd F Hultquist - Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL, USASteven M Wolinsky - Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL, USAGordon Dougan - University of CambridgeAndrew M L Lever - National University of SingaporeDeepti Gurdasani - Kirby Institute, University of New South Wales, Sydney, New South Wales, AustraliaHarriet Groom - University of CambridgeManjinder S Sandhu - Omnigen Biodata, Cambridge, UK. m.sandhu@imperial.ac.ukJacques Fellay - University of Lausanne
- Publication Details
- Nature (London), Vol.620, pp.1025-1030
- Publisher
- Springer Nature
- Identifiers
- 991005599162107891
- Copyright
- © 2023 Springer Nature Limited
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Citation topics
- 1 Clinical & Life Sciences
- 1.189 Genome Studies
- 1.189.455 Genome-Wide Association Studies
- Web Of Science research areas
- Genetics & Heredity
- ESI research areas
- Molecular Biology & Genetics