Department of Biotechnology, All India Institute of Medical Sciences, Ansari Nagar, India.
Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, India.
RNA Biol. 2023 Jan;20(1):805-816. doi: 10.1080/15476286.2023.2264003. Epub 2023 Oct 5.
DENV infection poses a major health concern globally and the pathophysiology relies heavily on host-cellular machinery. Although virus replication relies heavily on the host, the mechanistic details of DENV-host interaction is not fully characterized yet. Here, we are focusing on characterizing the mechanistic basis of virus-induced stress on the host cell. Specifically, we aim to characterize the role of the stress modulator ribonuclease Angiogenin during DENV infection. Our results suggested that the levels of Angiogenin are up-regulated in DENV-infected cells and the levels increase proportionately with DENV replication. Our efforts to knockdown Angiogenin using siRNA were unsuccessful in DENV-infected cells but not in mock-infected control. To further investigate the modulation between DENV replication and Angiogenin, we treated Huh7 cells with Ivermectin prior to DENV infection. Our results suggest a significant reduction in DENV replication specifically at the later stages as a consequence of Ivermectin treatment. Interestingly, Angiogenin levels were also found to be decreased proportionately. Our results suggest that Angiogenin modulation during DENV infection is important for DENV replication and pathogenesis.
登革热病毒感染是一个全球性的主要健康问题,其病理生理学在很大程度上依赖于宿主细胞机制。尽管病毒复制在很大程度上依赖于宿主,但登革热病毒与宿主相互作用的机制细节尚未完全阐明。在这里,我们专注于描述病毒诱导的宿主细胞应激的机制基础。具体来说,我们旨在描述在登革热病毒感染过程中,应激调节剂核糖核酸酶血管生成素的作用机制。我们的研究结果表明,登革热病毒感染的细胞中血管生成素的水平上调,并且其水平与登革热病毒的复制呈比例增加。我们试图使用 siRNA 敲低登革热病毒感染细胞中的血管生成素,但在 mock 感染对照细胞中并不成功。为了进一步研究登革热病毒复制和血管生成素之间的调节关系,我们在登革热病毒感染前用伊维菌素处理 Huh7 细胞。我们的结果表明,伊维菌素处理后,登革热病毒的复制明显减少,特别是在后期阶段。有趣的是,血管生成素的水平也相应降低。我们的结果表明,登革热病毒感染期间血管生成素的调节对于登革热病毒的复制和发病机制非常重要。