通过改变干扰素α/β受体功能水平,调整C57BL/6小鼠对正黄病毒的敏感性,以评估抗病毒药物。

IF 2.2 4区 医学 Q3 BIOCHEMICAL RESEARCH METHODS
John D. Morrey, Venkatraman Siddharthan
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引用次数: 0

摘要

本研究的目的是通过使用具有完整干扰素反应的野生型小鼠、1型干扰素α/β受体敲除小鼠或向野生型C57BL/6小鼠注射不同剂量的抗1型干扰素受体抗体(MAR1-5A3)来优化四种不同的正黄病毒在小鼠体内的感染性,以评估抗病毒药物。西尼罗河病毒能有效感染野生型 C57BL/6 小鼠并导致致死,而乌苏图病毒则要求 1 型干扰素受体功能完全缺失。鹿蜱病毒(2系Powassan病毒)和日本脑炎病毒需要通过调整MAR1-5A3抗体注射剂量来抑制1型干扰素反应。如果用 MAR1-5A3 抑制 1 型干扰素反应,就能观察到这两种病毒的挑战剂量反应死亡率、体重减轻和病毒滴度。相反,如果不注射 MAR1-5A3,这些疾病表型则不具有病毒挑战剂量反应性。通过这些不同的干扰素反应模型,确定了适当的致死率,从而确定 7-脱氮-2'-C-甲基腺苷对西尼罗河病毒和乌苏图病毒有很高的疗效,而对鹿蜱病毒和日本脑炎病毒的疗效较低。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Adjusting susceptibilities of C57BL/6 mice to orthoflaviviruses for evaluation of antiviral drugs by altering the levels of interferon alpha/beta receptor function
The purpose of this study was to optimize the infectivity of four different orthoflaviviruses in mice for evaluating antiviral drugs by using wild-type mice with intact interferon responses, type 1 interferon alpha/beta receptor knockout mice, or by injecting wild type C57BL/6 mice with varying doses of anti-type 1 interferon receptor antibody (MAR1-5A3) to optimize the infectivity and lethality. West Nile virus productively infected wild-type C57BL/6 mice to cause lethality, whereas Usutu virus required a complete absence of type 1 interferon receptor function. Deer tick virus (lineage 2 Powassan virus) and Japanese encephalitis viruses required a dampening of type 1 interferon responses by adjusting the doses of MAR1-5A3 antibody injections. Challenge dose-responsive mortality, weight loss, and viral titers of these two viruses were observed if the type 1 interferon responses were dampened with MAR1-5A3. Conversely, without MAR1-5A3 injections, these disease phenotypes were not viral challenge dose-responsive. From these different interferon-responsive models, the appropriate lethality was identified to determine that 7-deaza-2’-C-methyladenosine has high efficacy for West Nile and Usutu viruses, and low efficacy for deer tick and Japanese encephalitis viruses.
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来源期刊
CiteScore
5.80
自引率
0.00%
发文量
209
审稿时长
41 days
期刊介绍: The Journal of Virological Methods focuses on original, high quality research papers that describe novel and comprehensively tested methods which enhance human, animal, plant, bacterial or environmental virology and prions research and discovery. The methods may include, but not limited to, the study of: Viral components and morphology- Virus isolation, propagation and development of viral vectors- Viral pathogenesis, oncogenesis, vaccines and antivirals- Virus replication, host-pathogen interactions and responses- Virus transmission, prevention, control and treatment- Viral metagenomics and virome- Virus ecology, adaption and evolution- Applied virology such as nanotechnology- Viral diagnosis with novelty and comprehensive evaluation. We seek articles, systematic reviews, meta-analyses and laboratory protocols that include comprehensive technical details with statistical confirmations that provide validations against current best practice, international standards or quality assurance programs and which advance knowledge in virology leading to improved medical, veterinary or agricultural practices and management.
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