Characterization of tick-borne encephalitis virus isolated from a tick in central Hokkaido in 2017

Characterization of tick-borne encephalitis virus isolated from a tick in central Hokkaido in 2017
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DOI:
10.1099/jgv.0.001400
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发表时间:
2020-01-01
影响因子:
3.8
通讯作者:
Yoshii, Kentaro
Yoshii, Kentaro
中科院分区:
医学3区
文献类型:
--
作者:
Takahashi, Yuji;Kobayashi, Shintaro;Yoshii, Kentaro

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蜱传脑炎病毒(TBEV)是黄病毒科黄病毒属的一种人畜共患病毒。TBEV广泛分布于包括日本在内的欧亚大陆北方地区,可引起人类严重脑炎。蜱传脑炎(TBE)最近在北海道中部被报道,并且在北海道的大范围内检测到具有抗TBEV抗体的野生动物,尽管TBEV仅在北海道南部被分离。本研究以北海道中部地区的蜱为研究对象,进行了TBEV的分离调查。从札幌市收集的蜱(卵形硬蜱)中分离到一株,命名为札幌-17-Io 1。序列分析表明,分离株属于TBEV的远东亚型,并被归类为不同的亚群从大岛5-10,这是以前分离在南部北海道。札幌-17-Io 1在培养细胞和小鼠脑中显示出与Oshima 5-10相似的生长特性。脑内感染每种病毒的小鼠的死亡率相似,但接种札幌-17-Io 1的小鼠的存活时间显著长于接种Oshima 5-10的小鼠。这些结果表明,札幌-17-Io 1的神经毒力低于Oshima 5-10。使用感染性cDNA克隆,用来自札幌-17-Io 1的非结构基因编码基因替换来自Oshima 5-10的非结构基因,减弱了克隆病毒的神经致病性。这一结果表明,非结构蛋白决定了这两个菌株的神经毒力。我们的研究结果为评估北海道TBE流行地区的流行病学风险提供了重要的见解。
Tick-borne encephalitis virus (TBEV) is a zoonotic virus in the genus Flavivirus, family Flaviviridae. 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 (Ixodes ovatus) 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.