Sexual and Vertical Transmission of Zika Virus in anti-interferon receptor-treated Rag1-deficient mice.

Sexual and Vertical Transmission of Zika Virus in anti-interferon receptor-treated Rag1-deficient mice.
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DOI:
10.1038/s41598-017-07099-7
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发表时间:
2017-08-03
期刊:
影响因子:
4.6
通讯作者:
Peterson KE
Peterson KE
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Winkler CW;Woods TA;Rosenke R;Scott DP;Best SM;Peterson KE

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虽然寨卡病毒(ZIKV)主要由埃及伊蚊传播给人类,但也观察到从男性到女性以及从母亲到后代的人际传播。在本研究中,我们使用抗ifnar1处理Rag1−/−(AIR)小鼠,研究了ZIKV的性传播(STx)和垂直传播(VTx)。这些小鼠抑制了I型IFN反应,缺乏适应性免疫反应,导致临床疾病之前的长期感染。感染AIR的男性向未感染Ifnar1−/−的女性传播sikv的发生率大于50%,在早期时间点观察到阴道感染。在导致怀孕的情况下,在子宫和胎盘组织中也发现了病毒。在其他研究中,在AIR雌性小鼠中观察到病毒的VTx。具体而言,妊娠AIR母鼠的外周寨卡病毒感染导致胎儿和/或幼崽的大脑和/或淋巴结可检测到病毒。ZIKV的VTx是随机的,因为并非同一坝内的所有胎儿/幼崽都可检测到病毒,感染与母体/胎儿胎盘屏障的破坏无关。这为研究寨卡病毒对STx和VTx的屏障以及预防传播所必需的免疫反应提供了新的模型。
Although Zika virus (ZIKV) is primarily transmitted to humans by the Aedes aegypti mosquito, human-to-human transmission has also been observed from males-to-females as well as mother-to-offspring. In the current study, we studied both sexual transmission (STx) and vertical transmission (VTx) of ZIKV using anti-IFNAR1-treatment of Rag1 −/− (AIR) mice. These mice have suppressed type I IFN responses and lack adaptive immune responses, leading to a prolonged infection prior to clinical disease. STx of ZIKV from infected AIR males to naive Ifnar1 −/− females was observed with greater than 50% incidence, with infection observed in the vaginal tract at early time points. In the case of a resulting pregnancy, virus was also found in the uterus and placental tissue. In additional studies, VTx of virus was observed in AIR female mice. Specifically, peripheral ZIKV infection of pregnant AIR females resulted in detectable virus in brain and/or lymph nodes of fetuses and/or pups. VTx of ZIKV was stochastic, in that not all fetuses/pups within the same dam had detectable virus and infection was not associated with breakdown of maternal/fetal placental barrier. This provides a new model to study the barriers to STx and VTx of ZIKV and the immune responses essential to preventing transmission.
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