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Dendritic transport of tick-borne flavivirus RNA by neuronal granules affects development of neurological disease

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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
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)
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)

Submitter: 好井 健太朗

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