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恒河猴妊娠模型中两种寨卡病毒分离株的比较分析

Comparative Analysis of Two Zika Virus Isolates in a Rhesus Macaque Pregnancy Model.

作者信息

Jaeger Hannah K, Smith Jessica L, Parkins Christopher J, Haese Nicole N, Kreklywich Craig N, Denton Michael, Labriola Caralyn S, Axthelm Michael K, Barber-Axthelm Aaron, Chun Kim, Swanson Tonya, D'Mello Rahul J, Morgan Terry K, Smith Duncan R, Lo Jamie O, Hirsch Alec J, Roberts Victoria H J, Streblow Daniel N

机构信息

The Vaccine & Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, USA.

Division of Pathobiology & Immunology, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA.

出版信息

Viruses. 2025 May 27;17(6):762. doi: 10.3390/v17060762.

Abstract

Zika virus (ZIKV) infection during pregnancy can cause a broad range of neurological birth defects, collectively named Congenital Zika Syndrome (CZS). We have previously shown that infection with the Puerto Rican isolate PRVABC59 (ZIKV-PR) results in abnormal oxygen transport in the placenta due to villous damage and uterine vasculitis in a nonhuman primate model. To investigate whether this type of damage occurs with endemically circulating strains in Thailand, we investigated a CZS case isolate, MU1-2017 (ZIKV-TH), in pregnant rhesus macaques. Pregnant animals ( = 3 per group) were infected subcutaneously with either ZIKV-PR or ZIKV-TH at ~50 days gestation (GD) and monitored for 40 days post-infection (GD90). Similar courses of viremia and immune activation were observed for both viruses when compared to uninfected controls. In addition, both viruses induced changes to the placental architecture, including spiral artery remodeling and the development of infarctions. Similar levels of viral RNA were detected at necropsy in maternal and fetal tissues. Overall, our results show that the ZIKV-TH strain MU1-2017 behaves similarly to the ZIKV-PR strain, and, importantly, provide evidence of in-utero infection with an additional contemporary strain of ZIKV.

摘要

孕期感染寨卡病毒(ZIKV)可导致一系列广泛的神经学出生缺陷,统称为先天性寨卡综合征(CZS)。我们之前已经表明,在非人类灵长类动物模型中,感染波多黎各分离株PRVABC59(ZIKV-PR)会由于绒毛损伤和子宫血管炎而导致胎盘氧气运输异常。为了研究泰国流行的毒株是否会造成此类损伤,我们在怀孕的恒河猴身上研究了1例CZS病例分离株MU1-2017(ZIKV-TH)。怀孕动物(每组 = 3只)在妊娠约50天(GD)时皮下感染ZIKV-PR或ZIKV-TH,并在感染后40天(GD90)进行监测。与未感染的对照组相比,两种病毒的病毒血症和免疫激活过程相似。此外,两种病毒均引起胎盘结构变化,包括螺旋动脉重塑和梗死形成。尸检时在母体和胎儿组织中检测到相似水平的病毒RNA。总体而言,我们的结果表明,ZIKV-TH毒株MU1-2017的表现与ZIKV-PR毒株相似,重要的是,为子宫内感染另一种当代ZIKV毒株提供了证据。

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