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首页> 外文期刊>EBioMedicine >Zika Virus Infection in Dexamethasone-immunosuppressed Mice Demonstrating Disseminated Infection with Multi-organ Involvement Including Orchitis Effectively Treated by Recombinant Type I Interferons
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Zika Virus Infection in Dexamethasone-immunosuppressed Mice Demonstrating Disseminated Infection with Multi-organ Involvement Including Orchitis Effectively Treated by Recombinant Type I Interferons

机译：地塞米松免疫抑制小鼠中的寨卡病毒感染，表现出通过重组I型干扰素有效治疗的包括睾丸炎在内的多器官参与的传播感染。

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Abstract Background Disseminated or fatal Zika virus (ZIKV) infections were reported in immunosuppressed patients. Existing interferon-signaling/receptor-deficient mouse models may not be suitable for evaluating treatment effects of recombinant interferons. Methods We developed a novel mouse model for {ZIKV} infection by immunosuppressing BALB/c mice with dexamethasone. Results Dexamethasone-immunosuppressed male mice (6–8 weeks) developed disseminated infection as evidenced by the detection of ZIKV-NS1 protein expression and high viral loads in multiple organs. They had ≥ 10% weight loss and high clinical scores soon after dexamethasone withdrawal (10 dpi), which warranted euthanasia at 12 dpi. Viral loads in blood and most tissues at 5 dpi were significantly higher than those at 12 dpi (P < 0.05). Histological examination revealed prominent inflammatory infiltrates in multiple organs, and {CD45} + and {CD8} + inflammatory cells were seen in the testis. These findings suggested that clinical deterioration occurred during viral clearance by host immune response. Type I interferon treatments improved clinical outcome of mice (100% vs 0% survival). Conclusions Besides virus dissemination, inflammation of various tissues, especially orchitis, may be potential complications of {ZIKV} infection with significant implications on disease transmission and male fertility. Interferon treatment should be considered in patients at high risks for ZIKV-associated complications when the potential benefits outweigh the side effects of treatment.
机译：摘要背景在免疫抑制的患者中报告了传播性或致命性寨卡病毒（ZIKV）感染。现有的干扰素信号/受体缺陷型小鼠模型可能不适合评估重组干扰素的治疗效果。方法我们通过用地塞米松免疫抑制BALB / c小鼠，建立了{ZIKV}感染的新型小鼠模型。结果地塞米松免疫抑制的雄性小鼠（6-8周）发生了弥漫性感染，这可通过检测ZIKV-NS1蛋白表达和在多个器官中高病毒载量来证明。地塞米松戒断（10 dpi）后不久，他们的体重减轻≥10％，临床评分较高，这可确保在12 dpi时实现安乐死。 5 dpi时血液和大多数组织中的病毒载量显着高于12 dpi时（P <0.05）。组织学检查显示多个器官中明显的炎性浸润，并且在睾丸中发现了{CD45} +和{CD8} +炎性细胞。这些发现表明，在通过宿主免疫应答进行病毒清除过程中发生了临床恶化。 I型干扰素治疗可改善小鼠的临床结局（100％vs. 0％存活率）。结论除了传播病毒外，各种组织的炎症，特别是睾丸炎，可能是{ZIKV}感染的潜在并发症，对疾病传播和男性生育能力有重要影响。当潜在的利益大于治疗的副作用时，应考虑在ZIKV相关并发症高风险患者中考虑干扰素治疗。

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