Laboratory of Virology, Regional Centre for Biotechnology, NCR Biotech Science Cluster, 3rd Milestone, Gurgaon-Faridabad Expressway, Faridabad-121001, Haryana, India.
Department of Microbiology, Calcutta School of Tropical Medicine, 08, Chittaranjan Ave, Kolkata-700073, West Bengal, India.
J Gen Virol. 2023 Jan;104(1). doi: 10.1099/jgv.0.001823.
The lncRNA plays a vital role in mitochondrial function and antiviral response. We have previously identified as dysregulated lncRNAs and found an inverse correlation with interferon alpha-inducible protein 27 (IFI27) expression associated with developing dengue severity. However, the role of in dengue virus (DV) infection remains elusive. Here, we undertook a study to evaluate the functional consequences of and IFI27 modulation on antiviral response and viral replication in dengue infection. We observed that the knockdown of augmented IFI27 expression and antiviral response via the RIG-I pathway. Increased antiviral response leads to a decrease in dengue viral replication. Further study suggested that the knockdown of IFI27 augmented expression of the activating transcription factor 3 (ATF3), a negative regulator of antiviral response, and increased dengue virus replication suggesting an important role played by IFI27 in mediating antiviral response. RNA sequencing study confirmed several mitochondrial genes significantly altered upon knockdown of in DV-infected cells. We further verified the effect of knockdown on mitochondrial functions. We observed a reduced level of phospho-DRP1(S616) expression along with elongated mitochondria in DV2-infected cells. Further, knockdown or ectopic expression of IFI27 increased mitochondrial ROS production and cell death via activation of caspase 3. Our study points to the crucial role of and IFI27 in mediating antiviral response and mitochondrial dysfunction in dengue infection.
长链非编码 RNA 在线粒体功能和抗病毒反应中发挥着重要作用。我们之前已经确定了失调的长链非编码 RNA，并发现其与干扰素诱导蛋白 27（IFI27）的表达呈负相关，而 IFN27 的表达与登革热的严重程度有关。然而，在登革热病毒（DV）感染中，的作用仍不清楚。在这里，我们进行了一项研究，以评估和 IFI27 调节对抗病毒反应和登革热感染中病毒复制的功能后果。我们观察到，下调会通过 RIG-I 途径增强 IFI27 的表达和抗病毒反应。增强的抗病毒反应导致登革热病毒复制减少。进一步的研究表明，下调 IFI27 会增强激活转录因子 3（ATF3）的表达，ATF3 是抗病毒反应的负调节剂，增加登革热病毒复制，这表明 IFI27 在介导抗病毒反应中起着重要作用。RNA 测序研究证实，在 DV 感染细胞中下调后，有几个线粒体基因显著改变。我们进一步验证了下调对线粒体功能的影响。我们观察到在 DV2 感染的细胞中，磷酸化 DRP1（S616）的表达水平降低，线粒体拉长。此外，下调或过表达 IFI27 通过激活 caspase 3 增加线粒体 ROS 产生和细胞死亡。我们的研究表明，在登革热感染中，和 IFI27 在介导抗病毒反应和线粒体功能障碍方面起着至关重要的作用。
