Interferon ɛ restricts Zika virus infection in the female reproductive tract.
Interferon ɛ restricts Zika virus infection in the female reproductive tract.
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DOI：
10.1093/pnasnexus/pgad350
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发表时间：
2023-11
期刊：
影响因子：
--
通讯作者：
Chang, Theresa L.
中科院分区：
文献类型：
--
作者：
Xu, Chuan;Wang, Annie;Ebraham, Laith;Sullivan, Liam;Tasker, Carley;Pizutelli, Vanessa;Couret, Jennifer;Hernandez, Cyril;Kolli, Priyanka;Deb, Pratik Q.;Fritzky, Luke;Subbian, Selvakumar;Gao, Nan;Lo, Yungtai;Salvatore, Mirella;Rivera, Amariliz;Lemenze, Alexander;Fitzgerald-Bocarsly, Patricia;Tyagi, Sanjay;Lu, Wuyuan;Beaulieu, Aimee;Chang, Theresa L.
干扰素 ɛ (IFNɛ) 是一种独特的 I 型干扰素，与宿主防御性传播感染有关。寨卡病毒（ZIKV）是一种新出现的病原体，可以感染女性生殖道（FRT）并引起毁灭性的疾病，特别是在孕妇中。 IFNɛ 如何有助于预防体内 ZIKV 感染尚不清楚。在这项研究中，我们证明 IFNɛ 在宿主保护宿主免受小鼠阴道 ZIKV 感染方面发挥着关键作用。我们发现 IFNɛ 不仅在 FRT 中的上皮细胞中表达，而且在基线时或暴露于病毒或特定 Toll 样受体 (TLR) 激动剂后也由免疫细胞和基质细胞表达。 IFNɛ缺陷小鼠的子宫颈阴道道上皮边界和底层组织表现出异常，这些缺陷与阴道而非皮下 ZIKV 感染的易感性增加有关。 IFNɛ 缺乏导致 FRT 中 ZIKV 感染的程度、持续时间和深度增加。至关重要的是，阴道内给予重组 IFNɛ 可保护 Ifnɛ−/− 小鼠和高度易感的 Ifnar1−/− 小鼠免受阴道 ZIKV 感染，表明即使在没有其他 I 型 IFN 信号的情况下，IFNɛ 也足以以不依赖 IFNAR1 的方式提供保护。我们的研究结果揭示了 IFNɛ 在介导性接触中预防 ZIKV 传播的潜在关键作用。
Interferon ɛ (IFNɛ) 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 IFNɛ contributes to protection against ZIKV infection in vivo is unknown. In this study, we show that IFNɛ plays a critical role in host protection against vaginal ZIKV infection in mice. We found that IFNɛ 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. IFNɛ-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. IFNɛ deficiency resulted in an increase in magnitude, duration, and depth of ZIKV infection in the FRT. Critically, intravaginal administration of recombinant IFNɛ protected Ifnɛ−/− mice and highly susceptible Ifnar1−/− mice against vaginal ZIKV infection, indicating that IFNɛ 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 IFNɛ in mediating protection against the transmission of ZIKV in the context of sexual contact.
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DOI：
10.1126/science.1233321
发表时间：
2013-03-01
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Fung KY;Mangan NE;Cumming H;Horvat JC;Mayall JR;Stifter SA;De Weerd N;Roisman LC;Rossjohn J;Robertson SA;Schjenken JE;Parker B;Gargett CE;Nguyen HP;Carr DJ;Hansbro PM;Hertzog PJ
通讯作者：
Hertzog PJ
妊娠期寨卡病毒感染：病程和并发症的系统评价。
影响因子：
3.4
作者：
Chibueze EC;Tirado V;Lopes KD;Balogun OO;Takemoto Y;Swa T;Dagvadorj A;Nagata C;Morisaki N;Menendez C;Ota E;Mori R;Oladapo OT
通讯作者：
Oladapo OT
影响因子：
7.3
作者：
Kotredes KP;Thomas B;Gamero AM
通讯作者：
Gamero AM
影响因子：
3.1
作者：
Fichorova, RN;Desai, PJ;Genco, CA
通讯作者：
Genco, CA
影响因子：
4.4
作者：
Deb, Pratik;Dai, Jihong;Fitzgerald-Bocarsly, Patricia
通讯作者：
Fitzgerald-Bocarsly, Patricia