Paradoxical effects of chondroitin sulfate-E on Japanese encephalitis viral infection |
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Authors: | Kim Eunmi Okumura Megumi Sawa Hirofumi Miyazaki Tadaaki Fujikura Daisuke Yamada Shuhei Sugahara Kazuyuki Sasaki Michihito Kimura Takashi |
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Institution: | aDepartment of Molecular Pathobiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020, Japan;bDepartment of Bioresources, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020, Japan;cLaboratory of Proteoglycan Signaling and Therapeutics, Graduate School of Life Science, Frontier Research Center for Post-Genomic Science and Technology, Hokkaido University, Sapporo 001-0021, Japan;dGlobal COE Program, Hokkaido University, Sapporo, Japan |
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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. |
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Keywords: | Chondroitin sulfate E Japanese encephalitis virus Neural cell |
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