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Tick-borne flaviviruses alter membrane structure and replicate in dendrites of primary mouse neuronal cultures
Title: | Tick-borne flaviviruses alter membrane structure and replicate in dendrites of primary mouse neuronal cultures |
Authors: | Hirano, Minato Browse this author | Yoshii, Kentaro Browse this author →KAKEN DB | Sakai, Mizuki Browse this author | Hasebe, Rie Browse this author →KAKEN DB | Ichii, Osamu Browse this author →KAKEN DB | Kariwa, Hiroaki Browse this author →KAKEN DB |
Issue Date: | Apr-2014 |
Publisher: | Society for General Microbiology |
Journal Title: | Journal of General Virology |
Volume: | 95 |
Issue: | 4 |
Start Page: | 849 |
End Page: | 861 |
Publisher DOI: | 10.1099/vir.0.061432-0 |
PMID: | 24394700 |
Abstract: | Neurological diseases caused by encephalitic flaviviruses are severe and associated with high levels of mortality. However, detailed mechanisms of viral replication in the brain and features of viral pathogenesis remain poorly understood. We carried out a comparative analysis of replication of neurotropic flaviviruses: West Nile virus, Japanese encephalitis virus and tick-borne encephalitis virus (TBEV), in primary cultures of mouse brain neurons. All the flaviviruses multiplied well in primary neuronal cultures from the hippocampus, cerebral cortex and cerebellum. The distribution of viral-specific antigen in the neurons varied: TBEV infection induced accumulation of viral antigen in the neuronal dendrites to a greater extent than infection with other viruses. Viral structural proteins, non-structural proteins and dsRNA were detected in regions in which viral antigens accumulated in dendrites after TBEV replication. Replication of a TBEV replicon after infection with virus-like particles of TBEV also induced antigen accumulation, indicating that accumulated viral antigen was the result of viral RNA replication. Furthermore, electron microscopy confirmed that TBEV replication induced characteristic ultrastructural membrane alterations in the neurites: newly formed laminal membrane structures containing virion-like structures. This is the first report describing viral replication in and ultrastructural alterations of neuronal dendrites, which may cause neuronal dysfunction. These findings encourage further, work aimed at understanding the molecular mechanisms of viral replication in the brain and the pathogenicity of neurotropic flaviviruses. |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/58283 |
Appears in Collections: | 獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 好井 健太朗
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