关键词: Zika animal model tree shrew vaginal douching vaginal infection

Mesh : Animals Disease Models, Animal Female Tupaia Tupaiidae Vagina Zika Virus Zika Virus Infection

来  源:   DOI:10.3389/fcimb.2021.687338   PDF(Pubmed)

Abstract:
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.
摘要:
寨卡病毒(ZIKV)的性传播增加了其在女性生殖道中传播的风险,并对胎儿造成严重威胁。然而,现有的动物模型不适合调查性传播,ZIKV感染的动力学,复制,和脱落。在这项研究中评估了使用树sh作为ZIKV阴道感染的小动物模型。通过阴道内途径感染了ZIKVGZ01,共有23名性成熟的雌性树the。体重变化无显著差异,以及ZIKV感染动物和对照动物之间的温度。在血液中检测到病毒RNA载量,唾液,尿液,还有阴道冲洗.在22只动物的阴道灌洗中容易检测到ZIKVRNA(95.65%,22/23)在1dpi时,病毒载量从104.46到107.35拷贝/毫升,病毒载量的峰值出现在1dpi。关键炎症基因的表达,如IL6,8,CCL5,TNF-a,和CXCL9在ZIKV感染的动物的脾脏中增加。在目前的研究中,雌性树sh首次通过阴道途径成功感染了ZIKV。有趣的是,首先,ZIKV在感染的局部部位复制,然后在整个宿主体内传播,以发展强大的全身性感染并产生保护性免疫反应。这种小动物模型不仅对探索ZIKV性传播有价值,而且还可能有助于解释体内胎儿衰弱表现的原因。
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