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中国基因Ⅱ型赤羽病毒株(TJ2016)在小鼠模型中的致病性分析

Pathogenicity analysis of a Chinese Genogroup II Akabane virus strain (TJ2016) in mouse models.

作者信息

Wang Jingjing, Yu Ruyang, Wei Fang, Chen Dongjie, Wu Shaoqiang

机构信息

Institute of Animal Inspection and Quarantine, Chinese Academy of Quality and Inspection & Testing, Beijing, 100176, China.

出版信息

Virol J. 2025 Jun 7;22(1):186. doi: 10.1186/s12985-025-02819-2.

DOI:10.1186/s12985-025-02819-2
PMID:40483453
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12145599/
Abstract

BACKGROUND

Akabane virus (AKAV) is divided into five genogroups (I to V), and strains of different genogroups exhibit marked differences in pathogenicity. We isolated a genogroup II AKAV strain, TJ2016, in China in 2016, but its virulence remains unknown. The pathogenic potential of other genogroup II strains isolated in China also remains uncharacterized. The objectives of this study were to determine the pathogenicity of TJ2016.

METHODS

Kunming or Balb/c mice at 7 days or 8 weeks of age were inoculated with TJ2016 by intracerebral (IC), intraperitoneal (IP), subcutaneous (SC), or intramuscular (IM) routes. Clinical signs, pathological alterations, and AKAV distributions in the inoculated mice were monitored and analyzed.

RESULTS

Virus inoculations by the IC route resulted in 75% ~ 100% mortality of the inoculated mice regardless of the mouse strains or ages. Virus inoculations by the IP route killed 75% to 100% of the suckling mice but killed no adult mice. All the mice inoculated via SC and IM routes survived until the end of the trial. AKAV was detected only in the brains of the mice that died or were euthanized before the end of the experiment. The AKAV antigens were only identifiable within neuronal cells. Brain lesions such as proliferation and infiltration of microglial cells, perivascular cuffing (PVC) of lymphocytes and macrophages, neuronal degeneration/necrosis, vascular dilatation and congestion, etc., were observed only in the mice that died or were euthanized before the end of the experiment.

CONCLUSIONS

We characterized the virulence of TJ2016 by inoculating suckling and adult mice via different routes and established experimental mouse models, which holds significant implications for vaccine/drug development and further research on viral pathogenesis.

摘要

背景

赤羽病毒(AKAV)分为五个基因群(I至V),不同基因群的毒株在致病性上表现出显著差异。2016年我们在中国分离出一株基因群II的AKAV毒株TJ2016,但其毒力尚不清楚。在中国分离出的其他基因群II毒株的致病潜力也未得到表征。本研究的目的是确定TJ2016的致病性。

方法

对7日龄或8周龄的昆明小鼠或Balb/c小鼠通过脑内(IC)、腹腔内(IP)、皮下(SC)或肌肉内(IM)途径接种TJ2016。监测并分析接种小鼠的临床症状、病理变化和AKAV分布。

结果

无论小鼠品系或年龄如何,通过IC途径接种病毒导致接种小鼠的死亡率为75%至100%。通过IP途径接种病毒导致75%至100%的乳鼠死亡,但未导致成年小鼠死亡。所有通过SC和IM途径接种的小鼠存活至试验结束。仅在实验结束前死亡或被安乐死的小鼠大脑中检测到AKAV。AKAV抗原仅在神经元细胞内可识别。仅在实验结束前死亡或被安乐死的小鼠中观察到脑损伤,如小胶质细胞增殖和浸润、淋巴细胞和巨噬细胞的血管周围套袖样浸润(PVC)、神经元变性/坏死、血管扩张和充血等。

结论

我们通过不同途径接种乳鼠和成年小鼠来表征TJ2016的毒力,并建立了实验小鼠模型,这对疫苗/药物开发以及病毒发病机制的进一步研究具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/464f/12145599/4575c2695648/12985_2025_2819_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/464f/12145599/4575c2695648/12985_2025_2819_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/464f/12145599/68c70a782e46/12985_2025_2819_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/464f/12145599/fefd92aaa22c/12985_2025_2819_Fig5_HTML.jpg
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本文引用的文献

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A novel approach using IFNAR1 KO mice for assessing Akabane virus pathogenicity and vaccine efficacy.一种使用I型干扰素受体1基因敲除(IFNAR1 KO)小鼠评估赤羽病病毒致病性和疫苗效力的新方法。
Vaccine. 2025 Apr 19;53:127094. doi: 10.1016/j.vaccine.2025.127094. Epub 2025 Apr 11.
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Akabane virus isolated from biting midges and its infection in local domestic animal, Yunnan, China: a field and laboratory investigation.从云南中国当地家畜叮咬蠓中分离出的赤羽病毒及其感染情况:一项现场与实验室调查
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Investigating the reassortment potential and pathogenicity of the S segment in Akabane virus using a reverse genetics system.
利用反向遗传学系统研究赤羽病毒S基因片段的重配潜力和致病性。
BMC Vet Res. 2025 Jan 15;21(1):20. doi: 10.1186/s12917-024-04459-0.
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Generation of Stable Cell Lines Expressing Akabane Virus N Protein and Insight into Its Function in Viral Replication.表达赤羽病毒N蛋白的稳定细胞系的构建及其在病毒复制中功能的研究
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