AUTHOR=Yu Jianhai , Li Xujuan , Zhou Dongrui , Liu Xuling , He Xiaoen , Huang Sheng-He , Wu Qinghua , Zhu Li , Yu Linzhong , Yao Jinxiu , Zhang Bao , Zhao Wei 

TITLE=Vimentin Inhibits Dengue Virus Type 2 Invasion of the Blood-Brain Barrier

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.868407

DOI=10.3389/fcimb.2022.868407

ISSN=2235-2988

ABSTRACT=Dengue virus (DENV) causes dengue fever, which is prevalent in the tropical and subtropical regions and in recent years, has resulted in several major epidemics. Vimentin, a cytoskeletal component involved in DENV infection, is significantly reorganized during infection. However, the mechanism between DENV infection and Vimentin is still poorly understood. We generated vimentin knockout (Vim-KO) human brain microvascular endothelial cells (HBMECs) and a Vim-KO SV129 suckling mouse model, combined the dynamic vimentin changes observed in vitro and differences in disease course in vivo, to clarify the role of vimentin in DENV-2 infection. We found that the phosphorylation and solubility of vimentin changed dynamically during DENV-2 infection of HBMECs, suggesting regulation of vimentin by DENV-2 infection. The similar trends observed in phosphorylation and solubility of Vimentin showed that these characteristics are related. Compared with control cells, the DENV-2 viral load was significantly increased in Vim-KO HBMECs, and after DENV-2 infection, Vim-KO SV129 mice displayed more severe symptoms than normal SV129 mice, as well as higher viral loads in their serum and brain tissue, demonstrating that Vimentin can inhibit DENV-2 infection. Moreover, Vim-KO SV129 mice had more disordered cerebral cortical nerve cells, confirming that Vim-KO mice were more susceptible to DENV-2 infection, which causes severe brain damage. The findings of our study help clarify the mechanism by which vimentin inhibits DENV-2 infection and provides guidance for antiviral treatment strategy of DENV infection.