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Effect of the Rho GTPase inhibitor-1 on the entry of dengue serotype 2 virus into EAhy926 cells

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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.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (81671971, 81871641, 81972979, U1602223 and U1902210), Key Project of Beijing Natural Science Foundation B (KZ201810025035), the Scientific Research Plan of the Beijing Municipal Education Committee (KM201710025002) and the Foundation of Capital Medical University (PYZ19064).

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Authors and Affiliations

  1. Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China

    Dongying Fan, Zhaoyang Wang, Peigang Wang, Na Gao & Jing An

  2. Department of Experimental Animal, Capital Medical University, Beijing, 100069, China

    Na Wu

  3. Medical Research Center, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China

    Jing Zhang

  4. Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing, 100101, China

    Jing An

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  1. Dongying Fan
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NG designed the study. DYF, NW, JZ and NG performed the experiments. ZYW analyzed the data. NG wrote the paper. PGW and JA reviewed the manuscript. All authors read and approved the final manuscript.

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Correspondence to Na Gao.

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Fan, D., Wu, N., Zhang, J. et al. Effect of the Rho GTPase inhibitor-1 on the entry of dengue serotype 2 virus into EAhy926 cells. Mol Biol Rep 47, 9739–9747 (2020). https://doi.org/10.1007/s11033-020-05980-9

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