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Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine >
Peer-reviewed Journal Articles, etc >
A Critical Determinant of Neurological Disease Associated with Highly Pathogenic Tick-Borne Flavivirus in Mice
| Title: | A Critical Determinant of Neurological Disease Associated with Highly Pathogenic Tick-Borne Flavivirus in Mice |
| Authors: | Yoshii, Kentaro Browse this author →KAKEN DB | | Sunden, Yuji Browse this author →KAKEN DB | | Yokozawa, Kana Browse this author | | Igarashi, Manabu Browse this author →KAKEN DB | | Kariwa, Hiroaki Browse this author →KAKEN DB | | Holbrook, Michael R. Browse this author | | Takashima, Ikuo Browse this author →KAKEN DB |
| Issue Date: | May-2014 |
| Publisher: | American Society for Microbiology |
| Journal Title: | Journal of Virology |
| Volume: | 88 |
| Issue: | 10 |
| Start Page: | 5406 |
| End Page: | 5420 |
| Publisher DOI: | 10.1128/JVI.00421-14 |
| Abstract: | Tick-borne encephalitis virus (TBEV) and Omsk hemorrhagic fever virus (OHFV) are highly pathogenic tick-borne flaviviruses; TBEV causes neurological disease in humans, while OHFV causes a disease typically identified with hemorrhagic fever. Although TBEV and OHFV are closely related genetically, the viral determinants responsible for these distinct disease phenotypes have not been identified. In this study, chimeric viruses incorporating components of TBEV and OHFV were generated using infectious clone technology, and their pathological characteristics were analyzed in a mouse model to identify virus-specific determinants of disease. We found that only four amino acids near the C terminus of the NS5 protein were primarily responsible for the development of neurological disease. Mutation of these four amino acids had no effect on viral replication or histopathological features, including inflammatory responses, in mice. These findings suggest a critical role for NS5 in stimulating neuronal dysfunction and degeneration following TBEV infection and provide new insights into the molecular mechanisms underlying the pathogenesis of tick-borne flaviviruses. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/57349 |
| 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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