Division of Hematology-Oncology, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan.
School of Medicine, I-Shou University, Kaohsiung, Taiwan.
FASEB J. 2020 Jun;34(6):7283-7294. doi: 10.1096/fj.201902878R. Epub 2020 Apr 11.
MicroRNAs (miRNAs) have been reported to directly alter the virus life cycle and virus-host interactions, and so are considered promising molecules for controlling virus infection. In the present study, we observed that miR-155 time-dependently downregulated upon dengue virus (DENV) infection. In contrast, exogenous overexpression of miR-155 appeared to limit viral replication in vitro, suggesting that the low levels of miR-155 would be beneficial for DENV replication. In vivo, overexpression of miR-155 protected ICR suckling mice from the life-threatening effects of DENV infection and reduced virus propagation. Further investigation revealed that the anti-DENV activity of miR-155 was due to target Bach1, resulting in the induction of the heme oxygenase-1 (HO-1)-mediated inhibition of DENV NS2B/NS3 protease activity, ultimately leading to induction of antiviral interferon responses, including interferon-induced protein kinase R (PKR), 2'-5'-oligoadenylate synthetase 1 (OAS1), OAS2, and OAS3 expression, against DENV replication. Collectively, our results provide a promising new strategy to manage DENV infection by modulation of miR-155 expression.
MicroRNAs (miRNAs) 已被报道可直接改变病毒生命周期和病毒-宿主相互作用，因此被认为是控制病毒感染的有前途的分子。在本研究中，我们观察到 miR-155 在登革热病毒 (DENV) 感染时呈时间依赖性地下调。相比之下，外源性过表达 miR-155 似乎限制了病毒在体外的复制，表明 miR-155 的低水平有利于 DENV 的复制。在体内，miR-155 的过表达可保护 ICR 乳鼠免受 DENV 感染的致命影响，并减少病毒的传播。进一步的研究表明，miR-155 的抗 DENV 活性是由于靶向 Bach1，导致诱导血红素加氧酶-1 (HO-1) 介导的 DENV NS2B/NS3 蛋白酶活性抑制，最终导致诱导抗病毒干扰素反应，包括干扰素诱导的蛋白激酶 R (PKR)、2'-5'-寡聚腺苷酸合成酶 1 (OAS1)、OAS2 和 OAS3 的表达，从而抑制 DENV 的复制。总之，我们的研究结果为通过调节 miR-155 表达来管理 DENV 感染提供了一个有前途的新策略。
