title: Paradoxical effects of chondroitin sulfate-E on Japanese encephalitis viral infection.
abstract: Glycosaminoglycans (GAGs) have diverse functions in the body and are involved in viral infection. The purpose of this study was to evaluate the possible roles of the E-disaccharide units GlcAβ1-3GalNAc(4,6-O-disulfate) of chondroitin sulfate (CS), a GAG involved in neuritogenesis and neuronal migration, in Japanese encephalitis virus (JEV) infection. Soluble CS-E (sCS-E) derived from squid cartilage inhibited JEV infection in African green monkey kidney-derived Vero cells and baby hamster kidney-derived BHK cells by interfering with viral attachment. In contrast, sCS-E enhanced viral infection in the mouse neuroblastoma cell line Neuro-2a, despite the fact that viral attachment to Neuro-2a cells was inhibited by sCS-E. This enhancement effect in Neuro-2a cells seemed to be related to increased viral RNA replication and was also observed in a rat infection model in which intracerebral coadministration of sCS-E with JEV in 17-day-old rats resulted in higher brain viral loads than in rats infected without sCS-E administration. These results show the paradoxical effects of sCS-E on JEV infection in different cell types and indicate that potential use of sCS-E as an antiviral agent against JEV infection should be approached with caution considering its effects in the neuron, the major target of JEV.
authors.affiliation: Department of Molecular Pathobiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020, Japan.
authors.forename: Eunmi
authors.initials: E
authors.lastname: Kim
authors.forename: Megumi
authors.initials: M
authors.lastname: Okumura
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Sawa
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fujikura
authors.forename: Shuhei
authors.initials: S
authors.lastname: Yamada
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Sugahara
authors.forename: Michihito
authors.initials: M
authors.lastname: Sasaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Kimura
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D002809:Chondroitin Sulfates / Q000494:pharmacology*; D006224:Cricetinae; D004664:Encephalitis Virus, Japanese / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D051381:Rats; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; C038142:chondroitin sulfate glycosaminoglycan; D002809:Chondroitin Sulfates