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The variable region of the 3' untranslated region is a critical virulence factor in the Far-Eastern subtype of tick-borne encephalitis virus in mouse model

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Title: The variable region of the 3' untranslated region is a critical virulence factor in the Far-Eastern subtype of tick-borne encephalitis virus in mouse model
Authors: Sakai, Mizuki Browse this author
Yoshii, Kentaro Browse this author →KAKEN DB
Sunden, Yuji Browse this author →KAKEN DB
Yokozawa, Kana Browse this author
Hirano, Minato Browse this author
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: 823
End Page: 835
Publisher DOI: 10.1099/vir.0.060046-0
PMID: 24394696
Abstract: Tick-borne encephalitis virus (TBEV) is a major arbovirus that causes thousands of cases of severe neurological illness in humans annually. However, virulence factors and pathological mechanisms of TBEV remain largely unknown. To identify the virulence factors, we constructed chimeric viruses between two TBEV strains of the Far-Eastern subtype, Sofjin-HO (highly pathogenic) and Oshima 5-10 (low pathogenic). The replacement of the coding region for the structural and non-structural proteins from Sofjin into Oshima showed a partial increase of the viral pathogenicity in a mouse model. Oshima-based chimeric viruses with the variable region of the 3' UTR of Sofjin, which had a deletion of 207 nt, killed 100% of mice and showed almost the same virulence as Sofjin. Replacement of the variable region of the 3' UTR from Sofjin into Oshima did not increase viral multiplication in cultured cells and a mouse model at the early phase of viral entry into the brain. At the terminal phase of viral infection in mice, the virus titre of the Oshinna-based chimeric virus with the variable region of the 3' UTR of Sofjin reached a level identical to that of Sofjin and showed a similar histopathological change in the brain tissue. This is the first report to show that the variable region of the 3' UTR is a critical virulence factor in mice. These findings encourage further study to understand the mechanisms of the pathogenicity of TBEV, and to develop preventative and therapeutic strategies for tick-borne encephalitis.
Type: article (author version)
URI: http://hdl.handle.net/2115/58282
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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