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

Article scientifique 2020 Anglais

Résumé

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.

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Adland, E., Millar, J., Bengu, N., Muenchhoff, M., Fillis, R., Sprenger, K., Ntlantsana, V., Roider, J., Vieira, V., Govender, K., Adamson, J., Nxele, N., Ochsenbauer, C., Kappes, J., Mori, L., Lobenstein, J., Graza, Y., Chinniah, K., Kapongo, C., Bhoola, R., Krishna, M., Matthews, P., Poderos, R., Colomer-Lluch, M., Puertas, M., Prado, J., McKerrow, N., Archary, M., Ndung’u, T., Groll, A., Jooste, P., Martínez‐Picado, J., Altfeld, M., Goulder, P. (2020). Sex-specific innate immune selection of HIV-1 in utero is associated with increased female susceptibility to infection. https://doi.org/10.1038/s41467-020-15632-y

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Auteur(s)

Emily Adland Jane Millar Nomonde Bengu Maximilian Muenchhoff Rowena Fillis Kenneth Sprenger Vuyokasi Ntlantsana Julia Roider Vinícius Vieira Katya Govender John Adamson Nelisiwe Nxele Christina Ochsenbauer John C. Kappes Luisa Mori Jeroen van Lobenstein Yeney Graza Kogielambal Chinniah Constant Kapongo Roopesh Bhoola Malini Krishna Philippa C. Matthews Ruth Penya Poderos Marta Colomer-Lluch María C. Puertas Júlia G. Prado Neil McKerrow Moherndran Archary Thumbi Ndung’u Andreas Groll Pieter Jooste Javier Martínez‐Picado Marcus Altfeld Philip Goulder

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