1887

Abstract

Tick-borne encephalitis virus (TBEV) is a zoonotic virus in the genus , family . TBEV is widely distributed in northern regions of the Eurasian continent, including Japan, and causes severe encephalitis in humans. Tick-borne encephalitis (TBE) was recently reported in central Hokkaido, and wild animals with anti-TBEV antibodies were detected over a wide area of Hokkaido, although TBEV was only isolated in southern Hokkaido. In this study, we conducted a survey of ticks to isolate TBEV in central Hokkaido. One strain, designated Sapporo-17-Io1, was isolated from ticks () collected in Sapporo city. Sequence analysis revealed that the isolated strain belonged to the Far Eastern subtype of TBEV and was classified in a different subcluster from Oshima 5–10, which had previously been isolated in southern Hokkaido. Sapporo-17-Io1 showed similar growth properties to those of Oshima 5–10 in cultured cells and mouse brains. The mortality rate of mice infected intracerebrally with each virus was similar, but the survival time of mice inoculated with Sapporo-17-Io1 was significantly longer than that of mice inoculated with Oshima 5–10. These results indicate that the neurovirulence of Sapporo-17-Io1 was lower than that of Oshima 5–10. Using an infectious cDNA clone, the replacement of genes encoding non-structural genes from Oshima 5–10 with those from Sapporo-17-Io1 attenuated the neuropathogenicity of the cloned viruses. This result indicated that the non-structural proteins determine the neurovirulence of these two strains. Our results provide important insights for evaluating epidemiological risk in TBE-endemic areas of Hokkaido.

Funding
This study was supported by the:
  • Hiroaki Kariwa , Japan Agency for Medical Research and Development , (Award 19fk0108097h0801)
  • Kentaro Yoshii , Japan Agency for Medical Research and Development , (Award 18fk0108017h0803)
  • Kentaro Yoshii , Japan Agency for Medical Research and Development , (Award 19fk0108036h0003)
  • Kentaro Yoshii , Japan Society for the Promotion of Science , (Award JSPS and CAS under the Japan -Czech Research Cooperative Program)
  • Shintaro Kobayashi , Japan Society for the Promotion of Science , (Award 18K14574)
  • Kentaro Yoshii , Japan Society for the Promotion of Science , (Award 16K15032)
  • Kentaro Yoshii , Japan Society for the Promotion of Science , (Award 17H03910)
  • Kentaro Yoshii , Japan Society for the Promotion of Science , (Award 19K22353)
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2020-03-05
2020-06-04
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