Interferon ε restricts Zika virus infection in the female reproductive tract.
Interferon ε restricts Zika virus infection in the female reproductive tract.
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干扰素γ限制女性生殖道中的寨卡病毒感染。
DOI：
10.1101/2023.04.06.535968
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Lemenze,Alexan
中科院分区：
文献类型：
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作者：
Xu,Chuan;Wang,Annie;Ebraham,Laith;Sullivan,Liam;Tasker,Carley;Pizutelli,Vanessa;Couret,Jennifer;Hernandez,Cyril;Deb,PratikQ;Fritzky,Luke;Subbian,Selvakumar;Gao,Nan;Lo,Yungtai;Salvatore,Mirella;Rivera,Amariliz;Lemenze,Alexan
干扰素ɛ(干扰素ɛ)是一种独特的I型干扰素，与宿主对性传播感染的防御有关。寨卡病毒(ZIKV)是一种新出现的病原体，可感染女性生殖道(FRT)并导致破坏性疾病，特别是在孕妇中。干扰素ɛ如何在体内对寨卡病毒感染起到保护作用尚不清楚。在这项研究中，我们证明了干扰素ɛ在宿主抵抗小鼠阴道寨卡病毒感染中发挥了关键作用。我们发现，干扰素ɛ不仅在放射治疗中的上皮细胞中表达，而且在基线或暴露于病毒或Toll样受体激动剂后的免疫细胞和基质细胞中也有表达。干扰素ɛ基因缺陷的小鼠在宫颈阴道部的上皮缘和下层组织中表现出异常，这些缺陷与阴道感染的易感性增加有关，但与皮下感染寨卡病毒无关。干扰素ɛ缺乏导致ZIKV感染的程度、持续时间和深度增加。至关重要的是，经阴道注射重组干扰素ɛ可保护ɛ−/−小鼠和高度易感的IFNAR1小鼠免受阴道ZIKV感染，这表明即使在没有其他I型IFN信号的情况下，干扰素ɛ也足以提供保护，而且是以IFNAR1非依赖的方式提供的。我们的发现揭示了干扰素ɛ在性接触中介导预防寨卡病毒传播方面的潜在关键作用。
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 protectedIfnɛ−/−mice and highly susceptibleIfnar1−/−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.