title: Vimentin binding is critical for infection by the virulent strain of Japanese encephalitis virus.
abstract: Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, causes acute encephalitis with high mortality in humans. We used a pair of virulent (RP-9) and attenuated (RP-2ms) variants of JEV to pull down the cell surface molecules bound with JEV particle; their identities were revealed by LC-MS/MS analysis. One major protein bound with RP-9 and weakly with RP-2ms was identified as the intermediate filament protein vimentin. Infection of RP-9 but not that of RP-2ms was blocked by anti-vimentin antibodies and by recombinant-expressed vimentin proteins. Knockdown of vimentin expression reduced the levels of viral binding and viral production of RP-9, but not that of RP-2ms. The different vimentin dependency for JEV infection could be attributed to the major structural envelope protein, as the recombinant RP-9 with an E-E138K mutation became resistant to anti-vimentin blockage. Furthermore, RP-2ms mainly depended on cell surface glycosaminoglycans for viral binding and it became vimentin-dependent only when binding to glycosaminoglycans was blocked. Thus, we suggest that vimentin contributes to virulent JEV infection and might be a new target to intervene in this deadly infection.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Jian-Jong
authors.initials: JJ
authors.lastname: Liang
authors.forename: Chia-Yi
authors.initials: CY
authors.lastname: Yu
authors.forename: Ching-Len
authors.initials: CL
authors.lastname: Liao
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Lin
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004664:Encephalitis Virus, Japanese / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D051379:Mice; D011485:Protein Binding; D014746:Vimentin / Q000235:genetics / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D014774:Virulence
chemical_list: D006025:Glycosaminoglycans; D014746:Vimentin; D014759:Viral Envelope Proteins