TY - JOUR
T1 - Interferon ε restricts Zika virus infection in the female reproductive tract
AU - Xu, Chuan
AU - Wang, Annie
AU - Ebraham, Laith
AU - Sullivan, Liam
AU - Tasker, Carley
AU - Pizutelli, Vanessa
AU - Couret, Jennifer
AU - Hernandez, Cyril
AU - Kolli, Priyanka
AU - Deb, Pratik Q.
AU - Fritzky, Luke
AU - Subbian, Selvakumar
AU - Gao, Nan
AU - Lo, Yungtai
AU - Salvatore, Mirella
AU - Rivera, Amariliz
AU - Lemenze, Alexander
AU - Fitzgerald-Bocarsly, Patricia
AU - Tyagi, Sanjay
AU - Lu, Wuyuan
AU - Beaulieu, Aimee
AU - Chang, Theresa L.
N1 - Publisher Copyright:
© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences.
PY - 2023/11/1
Y1 - 2023/11/1
N2 - Interferon ε (IFNε) 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 IFNε contributes to protection against ZIKV infection in vivo is unknown. In this study, we show that IFNε plays a critical role in host protection against vaginal ZIKV infection in mice. We found that IFNε 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. IFNε-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. IFNε deficiency resulted in an increase in magnitude, duration, and depth of ZIKV infection in the FRT. Critically, intravaginal administration of recombinant IFNε protected Ifnε−/− mice and highly susceptible Ifnar1−/− mice against vaginal ZIKV infection, indicating that IFNε 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 IFNε in mediating protection against the transmission of ZIKV in the context of sexual contact.
AB - Interferon ε (IFNε) 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 IFNε contributes to protection against ZIKV infection in vivo is unknown. In this study, we show that IFNε plays a critical role in host protection against vaginal ZIKV infection in mice. We found that IFNε 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. IFNε-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. IFNε deficiency resulted in an increase in magnitude, duration, and depth of ZIKV infection in the FRT. Critically, intravaginal administration of recombinant IFNε protected Ifnε−/− mice and highly susceptible Ifnar1−/− mice against vaginal ZIKV infection, indicating that IFNε 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 IFNε in mediating protection against the transmission of ZIKV in the context of sexual contact.
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U2 - 10.1093/pnasnexus/pgad350
DO - 10.1093/pnasnexus/pgad350
M3 - Article
AN - SCOPUS:85178073046
SN - 2752-6542
VL - 2
JO - PNAS Nexus
JF - PNAS Nexus
IS - 11
M1 - pgad350
ER -