Effect of the Rho GTPase inhibitor-1 on the entry of dengue serotype 2 virus into EAhy926 cells
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ORIGINAL ARTICLE
Effect of the Rho GTPase inhibitor‑1 on the entry of dengue serotype 2 virus into EAhy926 cells Dongying Fan1 · Na Wu2 · Jing Zhang3 · Zhaoyang Wang1 · Peigang Wang1 · Na Gao1 · Jing An1,4 Received: 21 May 2020 / Accepted: 5 November 2020 © Springer Nature B.V. 2020
Abstract Dengue virus (DV) is the most rapidly spreading arbovirus in the world. Our previous studies indicated that Rac1, a kind of Rho GTPase, was related with the increased vascular permeability in DV infection. However, the molecular mechanisms that regulate the activity of the Rac1 pathway during DV infection is not fully understood yet. Recently, Rho-specific guanine nucleotide dissociated inhibitors (Rho GDIs), as a pivotal upstream regulator of Rho GTPase, attract our attention. To identify the role of GDI-1 in DV2 infection, the expression of GDI in Eahy926 cells was detected. Moreover, a GDI-1 down-regulated cell line was constructed to explore the correlation between GDI-1 and Rac1 and to further evaluate the function of GDI in DV life cycle. Our results indicated that DV2 infection could up-regulate GDI-1 expression, and down-regulation of GDI enhanced the activity of Rac1. In addition, down-regulated GDI-1 significantly inhibited all steps of DV2 replication cycle. GDI-1 plays an important role in DV2 infection via negatively regulating the activation of the Rac1-actin pathway. These results not only contribute to our further understanding of the pathogenesis of severe dengue but also provide further insight into the development of antiviral drugs. Keywords Dengue virus · Guanine nucleotide dissociated inhibitor · EAhy926 cells
Introduction Dengue is the most clinically common arbovirus infection in the world, and is caused by dengue virus (DV) from the genus Flavivirus in the family Flaviviridae. According to the recent epidemiologic studies, 390 million individuals are infected with DV globally per year, of which 96 million cases are symptomatic [1]. There are four related but distinct serotypes (DV 1–4). Infection with any of them can lead to the self-limited flu-like dengue fever (DF), and some DF patients might develop severe dengue, a potentially lethal complications previously known as dengue haemorrhagic * Na Gao [email protected] 1
Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China
2
Department of Experimental Animal, Capital Medical University, Beijing 100069, China
3
Medical Research Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
4
Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing 100101, China
fever (DHF) and dengue shock syndrome (DSS). Haemorrhage is one of typical manifestations for severe dengue, which is characterized with increased vascular permeability and plasma leakage. Usually, kinds of chemokines and cytokines released from dendritic cells and monocytes upon infection can activate the endothelium and then disrupt the endothelial barrier, which are contributed to th
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