A murine model of DC-SIGN humanization exhibits increased susceptibility against SARS-CoV-2

IF 2.6 4区医学 Q3 IMMUNOLOGY Microbes and Infection Pub Date : 2024-07-01 DOI:10.1016/j.micinf.2024.105344

Yeqing Tu , Yitai Fang , Rui Zheng , Dan Lu, Xiaolan Yang, Liangyan Zhang, Deyu Li, Yakun Sun, Wenjing Yu, Deyan Luo, Hui Wang

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Abstract

To generate a new murine model for virus, DC-SIGN gene in murine was humanized. In this study, we successfully generated a humanized C57BL/6N mouse model expressing human DC-SIGN (hDC-SIGN) using CRISPR/Cas9 technology, and evaluated its characters and susceptibility to virus. The humanized mice could survival as usual, and with normal physiological index just like the wild-type mice. Whereas, we found significant differences in the intestinal flora and metabolic profiles between wild-type mice and humanized mice. Following intranasal infection with SARS-CoV-2, hDC-SIGN mice exhibited significantly increased viral loads in the lungs and nasal turbinates, along with more severe lung damage. This phenomenon may be associated with differential lipid metabolism and Fcγ receptor-mediated phagocytosis in two mouse models. This study provides a useful tool for investigating the mechanisms of coronavirus infection and potential drug therapies against novel coronavirus.

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小鼠 DC-SIGN 人源化模型对 SARS-CoV-2 的易感性增强

为了产生一种新的小鼠病毒模型，我们对小鼠的 DC-SIGN 基因进行了人源化处理。本研究利用CRISPR/Cas9技术成功构建了表达人DC-SIGN（hDC-SIGN）的人源化C57BL/6N小鼠模型，并对其特征和对病毒的敏感性进行了评估。结果表明，人源化小鼠与野生型小鼠一样能正常生存，生理指标正常。但我们发现，野生型小鼠和人源化小鼠的肠道菌群和代谢谱存在明显差异。经鼻内感染SARS-CoV-2后，hDC-SIGN小鼠肺部和鼻甲中的病毒载量明显增加，肺部损伤更为严重。这一现象可能与两种小鼠模型中不同的脂质代谢和 Fcγ 受体介导的吞噬作用有关。这项研究为研究冠状病毒感染机制和针对新型冠状病毒的潜在药物疗法提供了有用的工具。

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来源期刊

Microbes and Infection 医学-病毒学

CiteScore

12.60

自引率

1.70%

发文量

审稿时长

40 days

期刊介绍： Microbes and Infection publishes 10 peer-reviewed issues per year in all fields of infection and immunity, covering the different levels of host-microbe interactions, and in particular: the molecular biology and cell biology of the crosstalk between hosts (human and model organisms) and microbes (viruses, bacteria, parasites and fungi), including molecular virulence and evasion mechanisms. the immune response to infection, including pathogenesis and host susceptibility. emerging human infectious diseases. systems immunology. molecular epidemiology/genetics of host pathogen interactions. microbiota and host "interactions". vaccine development, including novel strategies and adjuvants. Clinical studies, accounts of clinical trials and biomarker studies in infectious diseases are within the scope of the journal. Microbes and Infection publishes articles on human pathogens or pathogens of model systems. However, articles on other microbes can be published if they contribute to our understanding of basic mechanisms of host-pathogen interactions. Purely descriptive and preliminary studies are discouraged.