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Ebselen alleviates testicular pathology in mice with Zika virus infection and prevents its sexual transmission
PLoS Pathogens ( IF 5.5 ) Pub Date : 2018-02-15 , DOI: 10.1371/journal.ppat.1006854
Yogy Simanjuntak , Jian-Jong Liang , Si-Yu Chen , Jin-Kun Li , Yi-Ling Lee , Han-Chung Wu , Yi-Ling Lin

Despite the low case fatality, Zika virus (ZIKV) infection has been associated with microcephaly in infants and Guillain-Barré syndrome. Antiviral and vaccine developments against ZIKV are still ongoing; therefore, in the meantime, preventing the disease transmission is critical. Primarily transmitted by Aedes species mosquitoes, ZIKV also can be sexually transmitted. We used AG129 mice lacking interferon-α/β and -γ receptors to study the testicular pathogenesis and sexual transmission of ZIKV. Infection of ZIKV progressively damaged mouse testes, increased testicular oxidative stress as indicated by the levels of reactive oxygen species, nitric oxide, glutathione peroxidase 4, spermatogenesis-associated-18 homolog in sperm and pro-inflammatory cytokines including IL-1β, IL-6, and G-CSF. We then evaluated the potential role of the antioxidant ebselen (EBS) in alleviating the testicular pathology with ZIKV infection. EBS treatment significantly reduced ZIKV-induced testicular oxidative stress, leucocyte infiltration and production of pro-inflammatory response. Furthermore, it improved testicular pathology and prevented the sexual transmission of ZIKV in a male-to-female mouse sperm transfer model. EBS is currently in clinical trials for various diseases. ZIKV infection could be on the list for potential use of EBS, for alleviating the testicular pathogenesis with ZIKV infection and preventing its sexual transmission.



中文翻译:


Ebselen 缓解寨卡病毒感染小鼠的睾丸病理并预防其性传播



尽管病例死亡率较低,但寨卡病毒 (ZIKV) 感染与婴儿小头畸形和吉兰-巴利综合征有关。针对 ZIKV 的抗病毒和疫苗开发仍在进行中;因此,与此同时,预防疾病传播至关重要。 ZIKV 主要由伊蚊传播,也可以通过性传播。我们使用缺乏干扰素-α/β和-γ受体的AG129小鼠来研究ZIKV的睾丸发病机制和性传播。 ZIKV 感染逐渐损害小鼠睾丸,睾丸氧化应激增加,表现为精子中活性氧、一氧化氮、谷胱甘肽过氧化物酶 4、精子发生相关 18 同源物和促炎细胞因子(包括 IL-1β、IL-6)的水平和G-CSF。然后我们评估了抗氧化剂依布硒啉 (EBS) 在缓解 ZIKV 感染引起的睾丸病理方面的潜在作用。 EBS 治疗显着减少了 ZIKV 诱导的睾丸氧化应激、白细胞浸润和促炎症反应的产生。此外,它还改善了睾丸病理学,并在雄性至雌性小鼠精子移植模型中阻止了 ZIKV 的性传播。 EBS目前正处于针对多种疾病的临床试验中。 ZIKV 感染可能会被列入 EBS 的潜在用途清单,以减轻 ZIKV 感染引起的睾丸发病机制并预防其性传播。

更新日期:2018-02-16
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