title: Dysregulation of the β3 integrin-VEGFR2 complex in Hantaan virus-directed hyperpermeability upon treatment with VEGF.
abstract: Hantaviruses infect human endothelial cells (ECs) and are known to cause vascular-permeability-based diseases, including hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). The αvβ3 integrins, which are highly expressed on the surface of ECs, serve as hantavirus receptors. Specifically, the β3 integrin and vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) form a functional complex and interact with each other. Signaling through this complex causes cytoskeletal reorganization, which is one of the most important mechanisms underlying hyperpermeability. In this study, we show that VEGF dramatically enhances Hantaan virus (HTNV)-directed permeability and increases the reorganization of the cytoskeleton and the disruption of junctional organizations in an EC monolayer at 3 days postinfection. HTNV infection reduced the effect of VEGF on adhesion, migration, and the upregulation of β3 expression, but the infection alone upregulated the expression of β3 and VEGFR2. These results indicate that in addition to its role in blocking β3 integrin activation as reported previously, HTNV blocks the function of the complex of VEGFR2 and β3 integrin, and the dysfunction of the complex may contribute to cytoskeletal reorganization in an HTNV-directed hyperpermeability response to VEGF.
authors.affiliation: Center of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Pan
authors.forename: Lu
authors.initials: L
authors.lastname: Bai
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhuang
authors.forename: Chang-Xing
authors.initials: CX
authors.lastname: Huang
authors.forename: Jiu-Ping
authors.initials: JP
authors.lastname: Wang
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Yu
authors.forename: Xin
authors.initials: X
authors.lastname: Wei
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Ya-Yun
authors.initials: YY
authors.lastname: Nan
authors.forename: Dong-Qiang
authors.initials: DQ
authors.lastname: Yang
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Su
authors.forename: Ping-Zhong
authors.initials: PZ
authors.lastname: Wang
authors.forename: Xue-Fan
authors.initials: XF
authors.lastname: Bai
mesh_terms: D000818:Animals; D002199:Capillary Permeability; D002460:Cell Line; D002522:Chlorocebus aethiops; D003599:Cytoskeleton / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000821:virology; D018063:Hantaan virus / Q000235:genetics / Q000502:physiology*; D006480:Hemorrhagic Fever with Renal Syndrome / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics* / Q000378:metabolism; D014709:Vero Cells
chemical_list: D039661:Integrin beta3; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2