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.

登革热病毒（DV）是世界上传播最迅速的虫媒病毒。我们以前的研究表明，Rac1是一种Rho GTPase，与DV感染中血管通透性的增加有关。但是，尚不完全了解在DV感染期间调节Rac1途径活性的分子机制。最近，作为Rho GTPase关键的上游调节剂的Rho特异性鸟嘌呤核苷酸解离抑制剂（Rho GDI）引起了我们的注意。为了确定GDI-1在DV2感染中的作用，检测了Eahy926细胞中GDI的表达。此外，构建了GDI-1下调的细胞系，以探索GDI-1和Rac1之间的相关性，并进一步评估GD​​I在DV生命周期中的功能。我们的结果表明DV2感染可以上调GDI-1表达，GDI的下调增强了Rac1的活性。此外，下调的GDI-1显着抑制了DV2复制周期的所有步骤。GDI-1通过负调节Rac1-actin途径的激活在DV2感染中起重要作用。这些结果不仅有助于我们进一步了解重症登革热的发病机理，而且还为抗病毒药物的开发提供了进一步的见识。