Differential susceptibility of immunodeficient mice to MPXV infection and the impact of various inoculation routes

Xiaohan Wang; Shaowen Shi; Xiaoxuan Nie; Yongyang Sun; Jinglei Hu; Manlin He; Wenhao Ren; Yuxing Wang; Zhendong Guo; Gonghe Li; Changbo Ou; Xiao Li; Zongzheng Zhao

doi:10.1016/j.virs.2025.04.001

June 2025

. doi: 10.1016/j.virs.2025.04.001

Citation: Xiaohan Wang, Shaowen Shi, Xiaoxuan Nie, Yongyang Sun, Jinglei Hu, Manlin He, Wenhao Ren, Yuxing Wang, Zhendong Guo, Gonghe Li, Changbo Ou, Xiao Li, Zongzheng Zhao. Differential susceptibility of immunodeficient mice to MPXV infection and the impact of various inoculation routes .VIROLOGICA SINICA, 2025, 40(3) : 333-339. http://dx.doi.org/10.1016/j.virs.2025.04.001

不同免疫缺陷小鼠对MPXV感染的易感性及不同接种途径的影响

王笑焓 ^a,b ,
师少文 ^b,c ,
聂小萱 ^b,c ,
孙雍阳 ^b,d ,
胡静雷 ^b ,
何曼琳 ^b,c ,
任文浩 ^b,d ,
王玉星 ^b,d ,
郭振东 ^b ,
李恭贺 ^a ,
欧长波 ^a,, ,
李霄 ^b,, ,
赵宗正 ^b,,

a 广西大学;
b 中国农业科学院长春兽医研究所;
c 河北农业大学;
d 吉林农业大学

通讯作者： 欧长波, ouchangbo@gxu.edu.cn; 李霄, lixiao06@mails.jlu.edu.cn; 赵宗正, 329517286@qq.com
收稿日期： 2025-01-17
录用日期： 2025-04-02

摘要

猴痘病毒(MPXV)是正痘病毒属的一员，在2022年引起了全球大规模的爆发。开发MPXV感染的小鼠模型对于推进疫苗和治疗干预的研究至关重要。为了解决这个问题，我们对六种小鼠品系——严重联合免疫缺陷(SCID)小鼠、裸鼠、遗传性糖尿病(db/db)和肥胖(ob/ob)小鼠、C57BL/6J小鼠和BALB/c小鼠——对MPXV感染的易感性进行了比较研究。通过鼻内接种用MPXV感染小鼠品系，并在感染后监测体重变化和死亡率。此外，研究还评估了MPXV的组织分布和感染小鼠肺组织中的病理变化。结果表明，在感染MPXV后，SCID小鼠和裸鼠表现出显著的体重减轻，在SCID小鼠中观察到100%的死亡率，而在裸鼠中没有出现死亡。相比之下，其他小鼠品系没有显示出显著的体重减轻或死亡率。值得注意的是，SCID和裸鼠肺组织中的病毒载量在所有小鼠品系中最高。此外，我们研究了不同接种途径, I.N.: 滴鼻, I.P.: 腹腔注射, I.V.: 静脉注射对小鼠MPXV致病性的影响。结果显示，与鼻内和腹膜内途径相比，静脉内途径诱导了更显著的致病作用。这项研究为MPXV感染小鼠模型的发展提供了有价值的见解，为进一步研究MPXV的发病机制和治疗药物的开发提供了基础。
- 猴痘病毒
- , 小鼠
- , 易感性
- , 感染途径
- , 致病性

Differential susceptibility of immunodeficient mice to MPXV infection and the impact of various inoculation routes

Xiaohan Wang ^a,b ,
Shaowen Shi ^b,c ,
Xiaoxuan Nie ^b,c ,
Yongyang Sun ^b,d ,
Jinglei Hu ^b ,
Manlin He ^b,c ,
Wenhao Ren ^b,d ,
Yuxing Wang ^b,d ,
Zhendong Guo ^b ,
Gonghe Li ^a ,
Changbo Ou ^a,, ,
Xiao Li ^b,, ,
Zongzheng Zhao ^b,,

a. Guangxi University, Nanning, 530004, China;
b. Changchun Veterinary Research Institute, Chinese Academy of Agriculture Sciences, Changchun, 130122, China;
c. Hebei Agricultural University, Baoding, 071000, China;
d. Jilin Agricultural University, Changchun, 130118, China

Corresponding author: Changbo Ou, ouchangbo@gxu.edu.cn Xiao Li, lixiao06@mails.jlu.edu.cn Zongzheng Zhao, 329517286@qq.com
Received Date: 17 January 2025
Accepted Date: 02 April 2025

Abstract

Monkeypox virus (MPXV), a member of the Orthopoxvirus genus, caused a large-scale global outbreak in 2022. Developing mouse models for MPXV infection is crucial for advancing research on vaccines and therapeutic interventions. To address this, we conducted a comparative study on the susceptibility of six mouse strains—severe combined immune-deficiency (SCID), nude, genetically diabetic (db/db) and obese (ob/ob), C57BL/6J, and BALB/c—to MPXV infection. Mouse strains were infected with MPXV via intranasal inoculation, and body weight changes and mortality were monitored post-infection. Additionally, the tissue distribution of MPXV and the pathological changes in the lung tissues of the infected mice were evaluated. The results demonstrated that SCID and nude mice exhibited significant weight loss following MPXV infection, with 100 % mortality observed in SCID mice, while no mortality occurred in nude mice. In contrast, the other mouse strains showed no significant weight loss or mortality. Notably, the viral load in the lung tissues of SCID and nude mice was the highest among the tested strains. Furthermore, we investigated the impact of different inoculation routes—intranasal (I.N.), intraperitoneal (I.P.), and intravenous (I.V.)—on the pathogenicity of MPXV in mice. The results revealed that the intravenous route induced more pronounced pathogenic effects compared to the intranasal and intraperitoneal routes. In summary, this study provides valuable insights into the development of MPXV-infected mouse models, offering a foundation for further research on MPXV pathogenesis and therapeutic drug development.
- Monkeypox virus (MPXV)
- , Mouse
- , Susceptibility
- , Infection routes
- , Pathogenicity

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