A Mouse Model of MHV-1 Virus Infection for Study of Acute and Long COVID Infection.
A Mouse Model of MHV-1 Virus Infection for Study of Acute and Long COVID Infection.
复制标题
用于研究急性和长期新冠病毒感染的 MHV-1 病毒感染小鼠模型。
DOI：
10.1002/cpz1.896
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Paidas,MichaelJ
中科院分区：
文献类型：
--
作者：
Masciarella,AndrewD;DiGregorio,DibeM;Ramamoorthy,Rajalakshmi;Hussain,Hussain;Jayakumar,ArumugamR;Paidas,MichaelJ
由SARS-CoV-2引起的COVID-19对全球产生了重大影响。虽然疫苗和治疗减少了严重病例和死亡，但长期影响尚未得到充分了解。目前用于研究的模型，如非人类灵长类动物和转基因小鼠，价格昂贵，需要稀缺的生物安全3级（BSL-3）实验室，从而限制了它们的实用性。然而，小鼠肝炎病毒1（MHV-1）小鼠模型提供了一种有前途的替代方案。这种替代模型可以在更广泛的生物安全2级（BSL-2）实验室进行研究。此外，小鼠是负担得起的，易于处理，并利用MHV-1作为替代SARS-CoV-2消除了昂贵的转基因小鼠的需要。重要的是，MHV-1模型成功地重现了COVID-19相关的临床症状、体重减轻、急性期多器官病理变化和衰竭、不可逆的神经系统并发症和感染后的其他长期器官功能障碍，这些与COVID-19后的可用人体数据相似。为了帮助研究人员建立和使用MHV-1小鼠模型，该方案提供了全面的指导，包括动物准备，病毒感染诱导，临床观察，病理变化和组织分析的机制研究程序，从而对疾病机制和进展产生有价值的见解。通过采用MHV-1模型和提供的方案，研究人员可以有效地规避财政限制和BSL-3实验室的有限可用性，从而促进更容易获得和成本效益的方法来研究SARS-CoV-2病理生理学的潜在机制和探索潜在的治疗干预措施。© 2023 Wiley Periodicals LLC.基本方案：在A/J小鼠中诱导小鼠肝炎病毒1（MHV-1）感染支持方案1：组织学评价支持方案2：肝酶测量支持方案3：水通道蛋白表达的Western印迹分析支持方案4：mRNA测量支持方案5：免疫组织化学/免疫荧光支持方案6：组织水分测量
COVID‐19, caused by SARS‐CoV‐2, has had a significant global impact. While vaccines and treatments have reduced severe cases and deaths, the long‐term effects are not yet well understood. Current models used for research, such as non‐human primates and transgenic mice, are expensive and require scarce Biosafety Level‐3 (BSL‐3) laboratories, thereby limiting their practicality. However, the mouse hepatitis virus 1 (MHV‐1) mouse model offers a promising alternative. This surrogate model can be investigated in more widely available Biosafety Level‐2 (BSL‐2) laboratories. Furthermore, mice are affordable and easy to handle, and utilizing MHV‐1 as a surrogate for SARS‐CoV‐2 eliminates the need for costly transgenic mice. Importantly, the MHV‐1 model successfully recapitulates COVID‐19‐related clinical symptoms, weight loss, multiorgan pathological changes and failure in acute stages, irreversible neurological complications, and other long‐term organ dysfunction post‐infection, which are similar to available human data post‐COVID‐19. To assist researchers in establishing and using the MHV‐1 mouse model, this protocol offers comprehensive guidance encompassing procedures for animal preparation, induction of viral infection, clinical observation, pathological changes, and tissue analysis for mechanistic studies, thereby yielding valuable insights into disease mechanisms and progression. By adopting the MHV‐1 model and the provided protocols, researchers can effectively circumvent financial constraints and the limited availability of BSL‐3 laboratories, thus facilitating a more accessible and cost‐effective approach to investigating the underlying mechanisms of SARS‐CoV‐2 pathophysiology and exploring potential therapeutic interventions. © 2023 Wiley Periodicals LLC.Basic Protocol: Induction of mouse hepatitis virus 1 (MHV‐1) infection in A/J miceSupport Protocol 1: Histological evaluationSupport Protocol 2: Liver enzyme measurementSupport Protocol 3: Western blot analysis of aquaporin expressionSupport Protocol 4: mRNA measurementSupport Protocol 5: Immunohistochemistry/immunofluorescenceSupport Protocol 6: Tissue water measurement