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干扰素α/β受体基因敲除小鼠感染非洲马瘟病毒后的病理特征

Pathological features of African horse sickness virus infection in IFNAR mice.

作者信息

Jones Luke M, Hawes Phillippa C, Salguero Francisco J, Castillo-Olivares Javier

机构信息

The Pirbright Institute, Woking, United Kingdom.

United Kingdom Health Security Agency, UKHSA-Porton Down, Salisbury, United Kingdom.

出版信息

Front Vet Sci. 2023 Mar 30;10:1114240. doi: 10.3389/fvets.2023.1114240. eCollection 2023.

DOI:10.3389/fvets.2023.1114240
PMID:37065248
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10098166/
Abstract

African Horse Sickness (AHS) is a vector-borne viral disease of equids. The disease can be highly lethal with mortality rates of up to 90% in non-immune equine populations. The clinical presentation in the equine host varies, but the pathogenesis underlying this variation remains incompletely understood. Various small animal models of AHS have been developed over the years to overcome the financial, bio-safety and logistical constraints of studying the pathology of this disease in the target species. One of the most successful small animal models is based on the use of interferon-alpha gene knock-out (IFNAR) mice. In order to increase our understanding of African Horse Sickness virus (AHSV) pathogenesis, we characterised the pathology lesions of AHSV infection in IFNAR mice using a strain of AHSV serotype 4 (AHSV-4). We found AHSV-4 infection was correlated with lesions in various organs; necrosis in the spleen and lymphoid tissues, inflammatory infiltration in the liver and brain, and pneumonia. Significant viral antigen staining was only detected in the spleen and brain, however. Together these results confirm the value of the IFNAR mouse model for the study of the immuno-biology of AHSV infections in this particular system, and its usefulness for evaluating protective efficacy of candidate vaccines in preclinical studies.

摘要

非洲马瘟(AHS)是一种由媒介传播的马属动物病毒性疾病。该疾病具有高度致死性,在未免疫的马属动物群体中死亡率可达90%。马属动物宿主的临床表现各不相同,但其背后的发病机制仍未完全明确。多年来,人们开发了各种AHS的小动物模型,以克服在目标物种中研究该疾病病理学所面临的资金、生物安全和后勤方面的限制。最成功的小动物模型之一是基于使用干扰素-α基因敲除(IFNAR)小鼠。为了加深我们对非洲马瘟病毒(AHSV)发病机制的理解,我们使用一株4型AHSV(AHSV-4)对IFNAR小鼠中AHSV感染的病理损伤进行了特征描述。我们发现AHSV-4感染与多个器官的损伤相关;脾脏和淋巴组织出现坏死,肝脏和大脑有炎症浸润,以及肺炎。然而,仅在脾脏和大脑中检测到显著的病毒抗原染色。这些结果共同证实了IFNAR小鼠模型在该特定系统中研究AHSV感染免疫生物学的价值,以及其在临床前研究中评估候选疫苗保护效力的有用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbb9/10098166/e7eb73e4054a/fvets-10-1114240-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbb9/10098166/cb1a5320e018/fvets-10-1114240-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbb9/10098166/3fd260d8e05d/fvets-10-1114240-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbb9/10098166/6ef69d43e6d9/fvets-10-1114240-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbb9/10098166/e7eb73e4054a/fvets-10-1114240-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbb9/10098166/cb1a5320e018/fvets-10-1114240-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbb9/10098166/3fd260d8e05d/fvets-10-1114240-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbb9/10098166/6ef69d43e6d9/fvets-10-1114240-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbb9/10098166/e7eb73e4054a/fvets-10-1114240-g0004.jpg

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Apoptosis versus survival of African horse sickness virus serotype 4-infected horse peripheral blood mononuclear cells.
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Virulent African horse sickness virus serotype 4 interferes with the innate immune response in horse peripheral blood mononuclear cells in vitro.强毒型 4 型马传染性贫血病毒在体外干扰马外周血单核细胞的固有免疫反应。
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The immunogenicity of recombinant vaccines based on modified Vaccinia Ankara (MVA) viruses expressing African horse sickness virus VP2 antigens depends on the levels of expressed VP2 protein delivered to the host.基于表达非洲马瘟病毒 VP2 抗原的改良安卡拉痘苗病毒(MVA)的重组疫苗的免疫原性取决于递送到宿主的表达 VP2 蛋白的水平。
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