Recapitulating Zika Virus Infection in Vagina of Tree Shrew (Tupaia belangeri).
Recapitulating Zika Virus Infection in Vagina of Tree Shrew (Tupaia belangeri).
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DOI：
10.3389/fcimb.2021.687338
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发表时间：
2021
影响因子：
5.7
通讯作者：
Xia X
中科院分区：
文献类型：
--
作者：
Baloch Z;Shen Z;Zhang L;Feng Y;Li D;Zhang NN;Deng YQ;Yang C;Sun X;Dai J;Yang Z;Qin CF;Xia X
寨卡病毒（ZIKV）的性传播会增加其在女性生殖道传播的风险，并对胎儿造成严重威胁。然而，现有的动物模型并不适合研究性传播、寨卡病毒感染动态、复制和脱落。本研究评估了使用树鼩作为 ZIKV 阴道感染的小动物模型。共有 23 只性成熟雌性树鼩通过阴道内途径感染 ZIKV GZ01。 ZIKV 感染动物和对照动物的体重和体温变化没有显着差异。在血液、唾液、尿液和阴道冲洗液中检测到病毒 RNA 含量。 1 dpi 时，在 22 只动物（95.65%，22/23）的阴道灌洗液中容易检测到 ZIKV RNA，病毒载量范围为 104.46 至 107.35 拷贝/ml，病毒载量峰值出现在 1 dpi 时。在 ZIKV 感染动物的脾脏中，IL6、8、CCL5、TNF-a 和 CXCL9 等关键炎症基因的表达增加。在目前的研究中，雌性树鼩首次通过阴道途径成功感染寨卡病毒。有趣的是，ZIKV 首先在局部感染部位复制，然后扩散到整个宿主体内，形成强烈的全身感染并启动保护性免疫反应。这种小动物模型不仅对于探索 ZIKV 性传播有价值，还可能有助于解释胎儿体内衰弱表现的原因。
Sexual transmission of Zika Virus (ZIKV) elevates the risk of its dissemination in the female reproductive tract and causes a serious threat to the fetus. However, the available animal models are not appropriate to investigate sexual transmission, dynamics of ZIKV infection, replication, and shedding. The use of tree shrew as a small animal model of ZIKV vaginal infection was assessed in this study. A total of 23 sexually mature female tree shrews were infected with ZIKV GZ01 via the intravaginal route. There was no significant difference in change of body weight, and the temperature between ZIKV infected and control animals. Viral RNA loads were detected in blood, saliva, urine, and vaginal douching. ZIKV RNA was readily detected in vaginal lavage of 22 animals (95.65%, 22/23) at 1 dpi, and viral load ranged from 104.46 to 107.35 copies/ml, and the peak of viral load appeared at 1 dpi. The expression of key inflammatory genes, such as IL6, 8, CCL5, TNF-a, and CXCL9, was increased in the spleen of ZIKV infected animals. In the current study, female tree shrews have been successfully infected with ZIKV through the vaginal route for the first time. Interestingly, at first, ZIKV replicates at the local site of infection and then spreads throughout the host body to develop a robust systemic infection and mounted a protective immune response. This small animal model is not only valuable for exploring ZIKV sexual transmission and may also help to explain the cause of debilitating manifestations of the fetus in vivo.