Sex-specific innate immune selection of HIV-1 in utero is associated with increased female susceptibility to infection.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
14 04 2020
14 04 2020
Historique:
received:
22
10
2019
accepted:
16
03
2020
entrez:
15
4
2020
pubmed:
15
4
2020
medline:
25
7
2020
Statut:
epublish
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.
Identifiants
pubmed: 32286302
doi: 10.1038/s41467-020-15632-y
pii: 10.1038/s41467-020-15632-y
pmc: PMC7156749
doi:
Substances chimiques
Anti-Retroviral Agents
0
Interferons
9008-11-1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1767Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R01 AI133673
Pays : United States
Organisme : Wellcome Trust
ID : WT 110110
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT 104748MA
Pays : United Kingdom
Commentaires et corrections
Type : ErratumIn
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