Nogueira Clara de O, Lopes da Silva Mariana Oliveira, de Lima Emanuelle V, Christoff Raíssa Rilo, Gavino-Leopoldino Daniel, Lemos Felipe S, da Silva Nicolas E, Da Poian Andrea T, Assunção-Miranda Iranaia, Figueiredo Claudia P, Clarke Julia R
Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941902, RJ, Brazil.
Instituto de Microbiologia Paulo de Goes, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941902, RJ, Brazil.
iScience. 2024 Jun 5;27(7):110178. doi: 10.1016/j.isci.2024.110178. eCollection 2024 Jul 19.
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.
寨卡病毒（ZIKV）是一种嗜神经性黄病毒，可在多个组织中持续存在。ZIKV持续存在的后期后果以及是否会发生新一轮的活跃复制，仍未得到解决。在此，我们研究了新生期感染ZIKV的小鼠在成年后是否易发生病毒再激活。我们发现，当用免疫抑制药物治疗感染ZIKV的小鼠时，它们对化学诱导的癫痫发作的易感性增加。免疫抑制后，小鼠大脑中亚基因组黄病毒RNA（sfRNAs）的水平相对于基因组RNA的量有所增加，并且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体内ZIKV基因组RNA水平升高，这也导致了明显的睾丸损伤。这些发现表明，ZIKV在疾病急性期后很长时间仍可建立新一轮的活跃复制，因此应对暴露的患者进行监测，以确保病毒被彻底清除。
