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Sex-specific innate immune selection of HIV-1 in utero is associated with increased female susceptibility to infection

Author

Listed:
  • Emily Adland

    (Department of Paediatrics, University of Oxford)

  • Jane Millar

    (Department of Paediatrics, University of Oxford
    HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal)

  • Nomonde Bengu

    (Umkhuseli Innovation and Research Management)

  • Maximilian Muenchhoff

    (Max von Pettenkofer Institute, Virology, National Reference Center for Retroviruses, Faculty of Medicine, LMU München
    German Center for Infection Research (DZIF), Partner site Munich)

  • Rowena Fillis

    (Umkhuseli Innovation and Research Management)

  • Kenneth Sprenger

    (Umkhuseli Innovation and Research Management)

  • Vuyokasi Ntlantsana

    (Department of Medicine, University of KwaZulu-Natal)

  • Julia Roider

    (German Center for Infection Research (DZIF), Partner site Munich
    Ludwig-Maximilians-University)

  • Vinicius Vieira

    (Department of Paediatrics, University of Oxford)

  • Katya Govender

    (Africa Health Research Institute)

  • John Adamson

    (Africa Health Research Institute)

  • Nelisiwe Nxele

    (HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal)

  • Christina Ochsenbauer

    (Department of Medicine, University of Alabama at Birmingham)

  • John Kappes

    (Department of Medicine, University of Alabama at Birmingham
    Birmingham Veterans Affairs Medical Center, Research Service)

  • Luisa Mori

    (Department of Paediatrics, University of Oxford)

  • Jeroen Lobenstein

    (Stanger Hospital, KwaDukuza)

  • Yeney Graza

    (KwaZulu-Natal Department of Health)

  • Kogielambal Chinniah

    (Mahatma Gandhi Memorial Hospital)

  • Constant Kapongo

    (Queen Nandi Regional Hospital, Empangeni)

  • Roopesh Bhoola

    (Edendale Hospital, Pietermartizburg)

  • Malini Krishna

    (Edendale Hospital, Pietermartizburg)

  • Philippa C. Matthews

    (Nuffield Department of Medicine, University of Oxford)

  • Ruth Penya Poderos

    (IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP))

  • Marta Colomer Lluch

    (IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP))

  • Maria C. Puertas

    (IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP))

  • Julia G. Prado

    (IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP))

  • Neil McKerrow

    (KwaZulu-Natal Department of Health)

  • Moherndran Archary

    (Department of Paediatrics, University of KwaZulu-Natal)

  • Thumbi Ndung’u

    (HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal
    Africa Health Research Institute
    Ragon Institute of MGH, MIT, and Harvard, Cambridge)

  • Andreas Groll

    (TU Dortmund University, Faculty of Statistics)

  • Pieter Jooste

    (Department of Paediatrics, Kimberley Hospital)

  • Javier Martinez-Picado

    (IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP)
    University of Vic-Central University of Catalonia (UVic-UCC)
    Institució Catalana de Recerca i Estudis Avançats (ICREA))

  • Marcus Altfeld

    (Virus Immunology Unit, Heinrich-Pette-Institut)

  • Philip Goulder

    (Department of Paediatrics, University of Oxford
    HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal
    Africa Health Research Institute
    Ragon Institute of MGH, MIT, and Harvard, Cambridge)

Abstract

Female children and adults typically generate more efficacious immune responses to vaccines and infections than age-matched males, but also suffer greater immunopathology and autoimmune disease. We here describe, in a cohort of > 170 in utero HIV-infected infants from KwaZulu-Natal, South Africa, fetal immune sex differences resulting in a 1.5–2-fold increased female susceptibility to intrauterine HIV infection. Viruses transmitted to females have lower replicative capacity (p = 0.0005) and are more type I interferon-resistant (p = 0.007) than those transmitted to males. Cord blood cells from females of HIV-uninfected sex-discordant twins are more activated (p = 0.01) and more susceptible to HIV infection in vitro (p = 0.03). Sex differences in outcome include superior maintenance of aviraemia among males (p = 0.007) that is not explained by differential antiretroviral therapy adherence. These data demonstrate sex-specific innate immune selection of HIV associated with increased female susceptibility to in utero infection and enhanced functional cure potential among infected males.

Suggested Citation

  • Emily Adland & Jane Millar & Nomonde Bengu & Maximilian Muenchhoff & Rowena Fillis & Kenneth Sprenger & Vuyokasi Ntlantsana & Julia Roider & Vinicius Vieira & Katya Govender & John Adamson & Nelisiwe , 2020. "Sex-specific innate immune selection of HIV-1 in utero is associated with increased female susceptibility to infection," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15632-y
    DOI: 10.1038/s41467-020-15632-y
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