Interferon É restricts Zika virus infection in the female reproductive tract.
PNAS Nexus
; 2(11): pgad350, 2023 Nov.
Article
em En
| MEDLINE
| ID: mdl-37954158
ABSTRACT
Interferon É (IFNÉ) is a unique type I IFN that has been implicated in host defense against sexually transmitted infections. Zika virus (ZIKV), an emerging pathogen, can infect the female reproductive tract (FRT) and cause devastating diseases, particularly in pregnant women. How IFNÉ contributes to protection against ZIKV infection in vivo is unknown. In this study, we show that IFNÉ plays a critical role in host protection against vaginal ZIKV infection in mice. We found that IFNÉ was expressed not only by epithelial cells in the FRT but also by immune and stromal cells at baseline or after exposure to viruses or specific Toll-like receptor (TLR) agonists. IFNÉ-deficient mice exhibited abnormalities in the epithelial border and underlying tissue in the cervicovaginal tract, and these defects were associated with increased susceptibility to vaginal but not subcutaneous ZIKV infection. IFNÉ deficiency resulted in an increase in magnitude, duration, and depth of ZIKV infection in the FRT. Critically, intravaginal administration of recombinant IFNÉ protected IfnÉ-/- mice and highly susceptible Ifnar1-/- mice against vaginal ZIKV infection, indicating that IFNÉ was sufficient to provide protection even in the absence of signals from other type I IFNs and in an IFNAR1-independent manner. Our findings reveal a potentially critical role for IFNÉ in mediating protection against the transmission of ZIKV in the context of sexual contact.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
PNAS Nexus
Ano de publicação:
2023
Tipo de documento:
Article