The Infection of the Japanese Encephalitis Virus SA14-14-2 Strain Induces Lethal Peripheral Inflammatory Responses in IFNAR Deficiency Mice.
The Infection of the Japanese Encephalitis Virus SA14-14-2 Strain Induces Lethal Peripheral Inflammatory Responses in IFNAR Deficiency Mice.
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DOI：
10.3389/fmicb.2021.823825
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发表时间：
2021
影响因子：
5.2
通讯作者：
Jing Z
中科院分区：
文献类型：
--
作者：
Liu J;Jing W;Fang Y;He X;Chen G;Jia H;Wang J;Jing Z
日本脑炎病毒（JEV）是世界范围内蚊媒病毒性脑炎的主要原因。另一方面，脑炎以外的临床症状在JEV感染中更为普遍，这表明了外周病理生理学的相关性。本研究以SA 14 -14-2株感染IFNAR-/-小鼠，在BSL-2下研究了JEV的外周免疫发病机制。感染IFNAR-/-小鼠的体重和存活率显著降低。IFNAR-/-小鼠的肝脏和脾脏表现出明显的组织损伤和炎性细胞浸润。在器官中也有广泛的病毒复制。IFN-α/β蛋白表达在外周组织和血清中显著升高，尽管相关的干扰素刺激基因（ISG）在感染IFNAR-/-动物的脾脏和肝脏中保持较低水平。结果表明，脾组织中IL-6、TNF-α、MCP-1等炎性细胞因子表达上调，IFN-γ等炎性细胞因子表达上调。在SA 14 -14-2感染的IFNAR-/-小鼠的脾和肝中巨噬细胞和嗜中性粒细胞的浸润显著升高。然而，在组织损伤、病毒增殖或脑中IFNα/β和炎性细胞因子的产生方面没有显著差异。感染JEV SA 14 -14-2株导致IFNAR-/-小鼠出现致命的外周炎症反应和器官损伤，但无脑炎。我们的研究结果可能有助于阐明与临床JEV感染相关的外周免疫发病机制，并有助于开发治疗方案。
The Japanese encephalitis virus (JEV) is a leading cause of mosquito-borne viral encephalitis worldwide. Clinical symptoms other than encephalitis, on the other hand, are substantially more prevalent with JEV infection, demonstrating the relevance of peripheral pathophysiology. We studied the peripheral immunopathogenesis of JEV using IFNAR deficient (IFNAR–/–) mice infected with the SA14-14-2 strain under the BSL-2. The body weight and survival rate of infected-IFNAR–/–mice decreased significantly. Infected-IFNAR–/–mice’s liver and spleen demonstrated obvious tissue damage and inflammatory cell infiltration. There was also extensive viral replication in the organs. IFN-α/β protein expression was dramatically elevated in peripheral tissues and serum, although the related interferon-stimulated genes (ISGs) remained low in the spleen and liver of infected-IFNAR–/–animals. Consistently, the differentially expressed genes (DEGs) analysis using RNA-sequencing of spleens showed inflammatory cytokines upregulation, such as IL-6, TNF-α, and MCP-1, and IFN-γ associated cytokine storm. The infiltration of macrophages and neutrophils in the spleen and liver of SA14-14-2-infected IFNAR–/– mice was dramatically elevated. However, there was no significant difference in tissue damage, viral multiplication, or the production of IFNα/β and inflammatory cytokines in the brain. Infection with the JEV SA14-14-2 strain resulted in a lethal peripheral inflammatory response and organ damage without encephalitis in IFNAR–/– mice. Our findings may help shed light on the peripheral immunopathogenesis associated with clinical JEV infection and aid in developing treatment options.