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A Viral Polymerase Inhibitor Reduces Zika Virus Replication in the Reproductive Organs of Male Mice

机译:病毒聚合酶抑制剂可减少Zika病毒在雄性小鼠生殖器官中的复制。

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摘要

In humans, Zika virus and viral RNA have been detected in semen up to 2.2 months and 6 months post infection (pi), respectively. Although the contribution of sexual transmission to the spread of ZIKV is too low to sustain an outbreak, it can increase the risk of infection and the epidemic size as well as prolong the duration of an outbreak. In this study, we explored the potential of antivirals to serve as an effective strategy to prevent sexual transmission. Male AG129 mice infected with a ZIKV isolate from Suriname were treated with the nucleoside analog, 7-deaza-2′-C-methyladenosine (7DMA), that was previously shown to be efficacious in reducing ZIKV viremia and delaying ZIKV-induced disease in mice. Following treatment, viral RNA and infectious virus titers were consistently reduced in the male reproductive organs compared to vehicle-treated mice. This reduction of ZIKV loads in the testis was confirmed by the detection of lower levels of ZIKV antigens. Our data illustrate the value of this mouse model to validate the efficacy of new potential ZIKV drugs at the level of the male reproductive system.
机译:在人类中,分别在感染后长达2.2个月和6个月的精液中检测到寨卡病毒和病毒RNA。尽管性传播对ZIKV传播的贡献太低而无法维持爆发,但它可能增加感染的风险和流行的规模,并延长爆发的持续时间。在这项研究中,我们探索了抗病毒药作为预防性传播的有效策略的潜力。用核苷类似物7-deaza-2'-C-甲基腺苷(7DMA)处理感染了苏里南ZIKV分离株的雄性AG129小鼠,先前已证明其在降低ZIKV病毒血症和延缓ZIKV诱导的小鼠疾病方面有效。治疗后,与媒介物治疗的小鼠相比,雄性生殖器官中的病毒RNA和感染性病毒滴度持续降低。通过检测到较低水平的ZIKV抗原,证实了睾丸ZIKV载量的减少。我们的数据说明了该小鼠模型在雄性生殖系统水平上验证新型潜在ZIKV药物功效的价值。

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