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Dendritic transport of tick-borne flavivirus RNA by neuronal granules affects development of neurological disease
Title: | Dendritic transport of tick-borne flavivirus RNA by neuronal granules affects development of neurological disease |
Authors: | Hirano, Minato Browse this author | Muto, Memi Browse this author | Sakai, Mizuki Browse this author | Kondo, Hirofumi Browse this author | Kobayashi, Shintaro Browse this author →KAKEN DB | Kariwa, Hiroaki Browse this author →KAKEN DB | Yoshii, Kentaro Browse this author →KAKEN DB |
Keywords: | tick-borne encephalitis virus | flavivirus | neuropathogenicity | neuronal granule | dendritic mRNA |
Issue Date: | 12-Sep-2017 |
Publisher: | National Academy of Sciences. |
Journal Title: | Proceedings of the National Academy of Sciences of the United States of America (PNAS) |
Volume: | 114 |
Issue: | 37 |
Start Page: | 9960 |
End Page: | 9965 |
Publisher DOI: | 10.1073/pnas.1704454114 |
Abstract: | Neurological diseases caused by encephalitic flaviviruses are severe and associated with high levels of mortality. However, little is known about the detailed mechanisms of viral replication and pathogenicity in the brain. Previously, we reported that the genomic RNA of tick-borne encephalitis virus (TBEV), a member of the genus Flavivirus, is transported and replicated in the dendrites of neurons. In the present study, we analyzed the transport mechanism of the viral genome to dendrites. We identified specific sequences of the 5' untranslated region of TBEV genomic RNA that act as a cis-acting element for RNA transport. Mutated TBEV with impaired RNA transport in dendrites caused a reduction in neurological symptoms in infected mice. We show that neuronal granules, which regulate the transport and local translation of dendritic mRNAs, are involved in TBEV genomic RNA transport. TBEV genomic RNA bound an RNA-binding protein of neuronal granules and disturbed the transport of dendritic mRNAs. These results demonstrated a neuropathogenic virus hijacking the neuronal granule system for the transport of viral genomic RNA in dendrites, resulting in severe neurological disease. |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/70872 |
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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