Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on severe Infectious Disease, Kunming 650118, China.
Viruses. 2020 Feb 13;12(2):209. doi: 10.3390/v12020209.
Rotavirus (RV) is the major causes of severe diarrhea in infants and young children under five years of age. There are no effective drugs for the treatment of rotavirus in addition to preventive live attenuated vaccine. Recent evidence demonstrates that microRNAs (miRNAs) can affect RNA virus replication. However, the antiviral effect of miRNAs during rotavirus replication are largely unknown. Here, we determined that miR-7 is upregulated during RV replication and that it targets the RV NSP5 (Nonstructural protein 5). Results suggested that miR-7 affected viroplasm formation and inhibited RV replication by down-regulating RV NSP5 expression. Up-regulation of miR-7 expression is a common regulation method of different G-type RV-infected host cells. Then, we further revealed the antiviral effect of miR-7 in diarrhea suckling mice model. MiR-7 is able to inhibit rotavirus replication in vitro and in vivo. These data provide that understanding the role of cellular miR-7 during rotaviral replication may help in the identification of novel therapeutic small RNA molecule drug for anti-rotavirus.
轮状病毒(RV)是 5 岁以下婴幼儿严重腹泻的主要原因。除了预防用减毒活疫苗外,目前尚无针对轮状病毒的有效治疗药物。最近的证据表明,微小 RNA(miRNA)可以影响 RNA 病毒的复制。然而,miRNA 在轮状病毒复制过程中的抗病毒作用在很大程度上尚不清楚。在这里,我们确定 miR-7 在 RV 复制过程中上调,并且它靶向 RV NSP5(非结构蛋白 5)。结果表明,miR-7 通过下调 RV NSP5 表达影响病毒质形成并抑制 RV 复制。miR-7 表达的上调是不同 G 型 RV 感染宿主细胞的常见调节方式。然后,我们进一步揭示了 miR-7 在腹泻乳鼠模型中的抗病毒作用。miR-7 能够在体外和体内抑制轮状病毒复制。这些数据表明,了解细胞 miR-7 在轮状病毒复制过程中的作用可能有助于鉴定新型抗轮状病毒治疗性小 RNA 分子药物。