miR-155 induction is a marker of murine norovirus infection but does not contribute to control of replication in vivo.
miR-155 induction is a marker of murine norovirus infection but does not contribute to control of replication in vivo.
复制标题
DOI：
10.12688/wellcomeopenres.14188.1
复制
发表时间：
2018
影响因子：
--
通讯作者：
Goodfellow I
中科院分区：
文献类型：
--
作者：
Thorne L;Lu J;Chaudhry Y;Goodfellow I
背景资料：由于它们在微调细胞蛋白质表达中的作用，microRNA既促进病毒复制，又有助于一系列病毒的抗病毒反应。诺如病毒和microRNA机制之间的相互作用尚未研究。在这里，我们研究了小鼠诺如病毒（MNV）感染过程中microRNA表达的变化。 研究方法：使用基于RT-qPCR的阵列，我们分析了在两种允许细胞系（鼠巨噬细胞系RAW264.7和鼠小胶质细胞系BV-2）中用急性菌株MNV-1感染期间miRNA表达的变化。通过RT-qPCR，我们进一步证实并分析了感染细胞系、骨髓来源的巨噬细胞和从感染持久株MNV-3的小鼠收获的组织中miR-155表达的变化。使用miR-155敲除（KO）小鼠，我们研究了miR-155的缺失是否影响体内持续MNV-3感染期间的病毒复制和发病机制，并通过ELISA监测血清IgG应答的发展。 结果：我们鉴定了在感染过程中表达增加或减少的细胞特异性miRNA组。在两种细胞系中仅诱导了两种miRNA，miR-687和miR-155。与先天免疫有关的miR-155在骨髓来源的巨噬细胞和感染组织中也上调。MNV-3在miR-155敲除（KO）小鼠中建立了持续感染，观察到与野生型小鼠相当的分泌病毒和组织复制水平。然而，与野生型小鼠相比，miR-155 KO小鼠的血清抗MNV IgG水平显著降低。 结论：我们已经鉴定了一组随着MNV感染而表达变化的miRNAs。miR-155诱导是体外和体内MNV感染的标志物，但它并不有助于控制体内持续感染。这一发现表明，与miR-155缺失相关的免疫缺陷，如较低的血清IgG水平，对于控制持续性MNV-3感染也不重要。
Background: Due to their role in fine-tuning cellular protein expression, microRNAs both promote viral replication and contribute to antiviral responses, for a range of viruses. The interactions between norovirus and the microRNA machinery have not yet been studied. Here, we investigated the changes that occur in microRNA expression during murine norovirus (MNV) infection. Methods: Using RT-qPCR-based arrays, we analysed changes in miRNA expression during infection with the acute strain MNV-1 in two permissive cell lines, a murine macrophage cell line, RAW264.7, and a murine microglial cell line, BV-2. By RT-qPCR, we further confirmed and analysed the changes in miR-155 expression in the infected cell lines, bone-marrow derived macrophage, and tissues harvested from mice infected with the persistent strain MNV-3. Using miR-155 knockout (KO) mice, we investigated whether loss of miR-155 affected viral replication and pathogenesis during persistent MNV-3 infection in vivo and monitored development of a serum IgG response by ELISA. Results: We identified cell-specific panels of miRNAs whose expression were increased or decreased during infection. Only two miRNAs, miR-687 and miR-155, were induced in both cell lines. miR-155, implicated in innate immunity, was also upregulated in bone-marrow derived macrophage and infected tissues. MNV-3 established a persistent infection in miR-155 knockout (KO) mice, with comparable levels of secreted virus and tissue replication observed as for wildtype mice. However, serum anti-MNV IgG levels were significantly reduced in miR-155 KO mice compared to wildtype mice. Conclusions: We have identified a panel of miRNAs whose expression changes with MNV infection. miR-155 induction is a marker of MNV infection in vitro and in vivo, however it does not contribute to the control of persistent infections in vivo. This finding suggests that the immune defects associated with miR-155 deletion, such as lower serum IgG levels, are also not important for control of persistent MNV-3 infection.