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Nat Commun ; 11(1): 1767, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286302

RESUMO

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.


Assuntos
Infecções por HIV/imunologia , HIV-1/imunologia , HIV-1/patogenicidade , Imunidade Inata/fisiologia , Antirretrovirais/uso terapêutico , Estudos de Coortes , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , HIV-1/efeitos dos fármacos , Humanos , Imunidade Inata/genética , Transmissão Vertical de Doenças Infecciosas , Interferons/metabolismo , Estimativa de Kaplan-Meier , Masculino , Filogenia , Fatores Sexuais , Pesquisa Translacional Biomédica
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