IL2rg-/-基因敲除大鼠支持人RSV病毒的长期感染
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1.中国食品药品检定研究院动物资源研究所;2.北京大学医学部基础医学院病原生物学系;3.中国食品药品检定研究院安全评价研究所

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The National Key Technologies R&D Program of China


IL2rg-/- knockout rats support human RSV a prolonged infection
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1.Institute for Laboratory Animal Resources, NIFDC;2.Department of Microbiology & Infectious Disease Center,School of Basic Medical Sciences,Peking University Health Science Center;3.National Center for Safety Evaluation of Drugs, Institute for Food and Drug Safety Evaluation, National Institutes for Food and Drug Control (NIFDC)

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National Science and Technology Major Projects of Infectious Disease funds

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    摘要:

    人类呼吸道合胞病毒 (human respiratory syncytial virus, hRSV)是引起全世界婴幼儿、老人及部分成人呼吸道疾病和死亡的主要病原体之一。动物模型在疫苗、治疗性药物评价中均发挥重要作用,包括黑猩猩等非人灵长类在内的多种动物均被用于构建hRSV的感染模型。但大多数动物模型的半受纳性特性及感染持续时间短等缺陷,阻碍了它们在 hRSV 发病机制和治疗开发中的应用。本文基于TALENs技术建立了IL2rg基因敲除的大鼠模型。 通过鼻内接种 hRSV 后,纯合的IL2rg敲除 (IL2rg?/?)大鼠的呼吸道内能保持较高的病毒载量,鼻腔中病毒的平均峰值滴度能快速升至 1?010 拷贝/g,至第5 周时,病毒依然能维持复制,病毒载量亦可达到 1?07拷贝/g。本文建立的可遗传的免疫缺陷大鼠模型,其性状稳定且易于生产,有利于疾病模型的标准化;较小鼠而言,大鼠具有体形较大、更利于采集足量临床样本的优势,该IL2rg?/?大鼠模型可用于hRSV传播和发病机制研究,是评估治疗方法的有用工具。

    Abstract:

    Human respiratory syncytial virus (hRSV) is the second leading aetiology of lower respiratory infection deaths in the world. Disease animal models play an important role in the development of vaccine and therapeutic drugs, and a variety of animals, including non-human primates such as chimpanzees, have been made to develop models of hRSV infection. However, the limitations such as semi-permissiveness and short duration of infection have impeded their applications in both the pathogenesis of hRSV and therapeutics development. Here, we presented an hRSV infection model based on IL2rg gene deficient rat using TALEN technology. IL2rg-/- knockout rats can sustain high viral loads in nasal cavity upon intranasal inoculation with hRSV. The average peak titer rapidly reached 1?010 copies/g in nasal tissue, as well as 1?07 copies/g up to 5 weeks post infection. Since IL2rg-/- knockout rats is genetically heritable, with stable traits and easy production, which facilitate the standardization of disease models. Compared with mice, rats have the advantages of being larger and more convenient for collecting sufficient samples. This IL2rg-/- rat model can be used to study the transmission and pathogenesis of hRSV and is a useful tool for evaluating therapies.

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  • 收稿日期:2023-07-06
  • 最后修改日期:2024-01-03
  • 录用日期:2024-01-16
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