title: Downregulation of beta1 integrins by Ebola virus glycoprotein: implication for virus entry.
abstract: Filoviruses, including Ebola virus, are cytotoxic. To investigate the role of the Ebola virus glycoprotein (GP) in this cytopathic effect, we transiently expressed the GP in human kidney 293T cells. Expression of wild-type GP, but not the secretory form of the molecule lacking a membrane anchor, induced rounding and detachment of the cells, as did a chimeric GP containing its ectodomain and influenza virus hemagglutinin transmembrane-cytoplasmic domain. These results indicate that the GP ectodomain and its anchorage to the membrane are required for GP-induced morphologic changes in host cells. Since cell rounding and detachment could be associated with reduced levels of cell adhesion molecules, we also studied the expression of integrins, which are major molecules for adhesion to extracellular matrices, and found that the beta1 integrin group is downregulated by the GP. This result was further extended by experiments in which anti-beta1 monoclonal antibodies or purified integrins inhibited the infectivity of vesicular stomatitis virus pseudotyped with the GP. We suggest that integrins, especially the beta1 group, might interact with the GP and perhaps be involved in Ebola virus entry into cells.
authors: Laboratory of Microbiology, Graduate School of Veterinary Medicine, Sapporo, 060-0818, Japan.
authors: A
authors: A
authors: Takada
authors: S
authors: S
authors: Watanabe
authors: H
authors: H
authors: Ito
authors: K
authors: K
authors: Okazaki
authors: H
authors: H
authors: Kida
authors: Y
authors: Y
authors: Kawaoka
mesh_terms: D002460:Cell Line; D002678:Chimera; D003588:Cytopathogenic Effect, Viral; D015536:Down-Regulation; D029043:Ebolavirus / Q000235:genetics* / Q000378:metabolism; D005434:Flow Cytometry; D006023:Glycoproteins / Q000032:analysis / Q000235:genetics*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D019012:Integrin beta1 / Q000276:immunology / Q000378:metabolism*; D009154:Mutation; D014162:Transfection
chemical_list: D006023:Glycoproteins; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D019012:Integrin beta1