title: Sphingomyelin generated by sphingomyelin synthase 1 is involved in attachment and infection with Japanese encephalitis virus.
abstract: Japanese encephalitis virus (JEV) is a mosquito-borne RNA virus which infects target cells via the envelope protein JEV-E. However, its cellular targets are largely unknown. To investigate the role of sphingomyelin (SM) in JEV infection, we utilized SM-deficient immortalized mouse embryonic fibroblasts (tMEF) established from SM synthase 1 (SMS1)/SMS2 double knockout mice. SMS deficiency significantly reduced both intracellular and extracellular JEV levels at 48 h after infection. Furthermore, after 15 min treatment with JEV, the early steps of JEV infection such as attachment and cell entry were also diminished in SMS-deficient tMEFs. The inhibition of JEV attachment and infection were recovered by overexpression of SMS1 but not SMS2, suggesting SMS1 contributes to SM production for JEV attachment and infection. Finally, intraperitoneal injection of JEV into SMS1-deficient mice showed an obvious decrease of JEV infection and its associated pathologies, such as meningitis, lymphocyte infiltration, and elevation of interleukin 6, compared with wild type mice. These results suggest that SMS1-generated SM on the plasma membrane is related in JEV attachment and subsequent infection, and may be a target for inhibition of JEV infection.
authors.affiliation: Department of Life Science, Medical Research Institute, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Taniguchi
authors.affiliation: Department of Life Science, Medical Research Institute, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Tasaki
authors.affiliation: Histology Laboratory, Research Support Center, Medical Research Institute, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ninomiya
authors.affiliation: Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293, Japan.|Graduate School of Arts and Sciences, University of Tokyo, Komaba, Meguro-ku, Tokyo, 153-8902, Japan.
authors.forename: Yoshibumi
authors.initials: Y
authors.lastname: Ueda
authors.affiliation: Department of Advanced Prosthodontics, Graduate School of Biomedical &Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Koh-Ichi
authors.initials: KI
authors.lastname: Kuremoto
authors.affiliation: Department of Applied Biochemistry and Food Sciences, Faculty of Agriculture, Saga University, Saga 840-8502, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Mitsutake
authors.affiliation: Laboratory of Biomembrane and Biofunction Chemistry, Faculty of Advanced Life Sciences, Hokkaido University, Kita 21-jo, Nishi 11-chome, Kita-ku, Sapporo 001-0021, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Igarashi
authors.affiliation: Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Okazaki
authors.affiliation: Department of Life Science, Medical Research Institute, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takegami
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000821:virology; D002462:Cell Membrane / Q000821:virology; D002522:Chlorocebus aethiops; D004664:Encephalitis Virus, Japanese / Q000472:pathogenicity*; D004672:Encephalitis, Japanese / Q000473:pathology / Q000821:virology; D005347:Fibroblasts / Q000821:virology; D054884:Host-Pathogen Interactions / Q000502:physiology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013109:Sphingomyelins / Q000378:metabolism*; D017855:Transferases (Other Substituted Phosphate Groups) / Q000235:genetics / Q000378:metabolism*; D014709:Vero Cells; D053585:Virus Attachment
chemical_list: D013109:Sphingomyelins; C556686:Sgms1 protein, mouse; D017855:Transferases (Other Substituted Phosphate Groups); C543123:Sgms2 protein, mouse