Abstract:
Zika virus (ZIKV) is a neurotropic flavivirus that can persist in several tissues. The late consequences of ZIKV persistence and whether new rounds of active replication can occur, remain unaddressed. Here, we investigated whether neonatally ZIKV-infected mice are susceptible to viral reactivation in adulthood. We found that when ZIKV-infected mice are treated with immunosuppressant drugs, they present increased susceptibility to chemically induced seizures. Levels of subgenomic flavivirus RNAs (sfRNAs) were increased, relative to the amounts of genomic RNAs, in the brains of mice following immunosuppression and were associated with changes in cytokine expression. We investigated the impact of immunosuppression on the testicles and found that ZIKV genomic RNA levels are increased in mice following immunosuppression, which also caused significant testicular damage. These findings suggest that ZIKV can establish new rounds of active replication long after acute stages of disease, so exposed patients should be monitored to ensure complete viral eradication.
摘要:
寨卡病毒(ZIKV)是一种嗜神经黄病毒,可以在几种组织中持续存在。ZIKV持久性的后期后果以及是否可以发生新一轮的主动复制,仍未解决。这里,我们调查了新生感染ZIKV的小鼠在成年期是否对病毒再激活敏感.我们发现,当感染ZIKV的小鼠用免疫抑制药物治疗时,它们对化学诱发的癫痫发作的易感性增加。亚基因组黄病毒RNA(sfRNA)的水平增加,相对于基因组RNA的数量,在免疫抑制后小鼠的大脑中,并与细胞因子表达的变化有关。我们研究了免疫抑制对睾丸的影响,发现免疫抑制后小鼠的ZIKV基因组RNA水平增加,这也造成了严重的睾丸损伤。这些发现表明,ZIKV可以在疾病的急性期后很长一段时间内建立新一轮的主动复制,因此,应监测暴露的患者,以确保病毒完全根除。