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

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

doi:10.1016/j.micinf.2024.105344

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

Microbes Infect. 2024 Apr 24:105344. doi: 10.1016/j.micinf.2024.105344. Online ahead of print.

Authors

Yeqing Tu¹, Yitai Fang¹, Rui Zheng¹, Dan Lu¹, Xiaolan Yang¹, Liangyan Zhang¹, Deyu Li¹, Yakun Sun¹, Wenjing Yu¹, Deyan Luo¹, Hui Wang²

Affiliations

¹ State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.
² State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China. Electronic address: geno0109@vip.sina.com.

PMID: 38670218
DOI: 10.1016/j.micinf.2024.105344

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.

Keywords: DC-SIGN; Humanization; Infection; SARS-CoV-2.