Construction and validation of a mouse model for studying severe human adenovirus infections

Dingbin Chen; Yuqian Yan; Ting Mei; Peipei Yang; Siqi Deng; Yiqiang Li; Tie Zhao; Ning Xin; Biyan Duan; Weifeng Liang; Yuemei Yang; Wei Zhao; Donald Seto; Junxian Ou; Qiwei Zhang

doi:10.1016/j.virs.2024.11.001

December 2024

Citation: Dingbin Chen, Yuqian Yan, Ting Mei, Peipei Yang, Siqi Deng, Yiqiang Li, Tie Zhao, Ning Xin, Biyan Duan, Weifeng Liang, Yuemei Yang, Wei Zhao, Donald Seto, Junxian Ou, Qiwei Zhang. Construction and validation of a mouse model for studying severe human adenovirus infections .VIROLOGICA SINICA, 2024, 39(6) : 963-973. http://dx.doi.org/10.1016/j.virs.2024.11.001

Construction and validation of a mouse model for studying severe human adenovirus infections

Dingbin Chen ^a ,
Yuqian Yan ^b,c ,
Ting Mei ^a ,
Peipei Yang ^a ,
Siqi Deng ^a ,
Yiqiang Li ^a ,
Tie Zhao ^a ,
Ning Xin ^a ,
Biyan Duan ^a ,
Weifeng Liang ^a ,
Yuemei Yang ^d ,
Wei Zhao ^b ,
Donald Seto ^e ,
Junxian Ou ^{a,f,g
,,} ,
Qiwei Zhang ^{a,g
,,}

cstr: 32224.14.j.virs.2024.11.001

a. Institute of Medical Microbiology, Department of Immunology and Microbiology, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China;
b. BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China;
c. Department of Clinical Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510620, China;
d. South Yunnan Central Hospital (Honghe First People's Hospital), Mengzi, Yunnan, 661100, China;
e. Bioinformatics and Computational Biology Program, School of Systems Biology, George Mason University, Manassas, VA, 20110, USA;
f. The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510310, China;
g. Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education, Guangzhou, 510632, China

Corresponding author: Junxian Ou, junxianou1993@jnu.edu.cn
Qiwei Zhang, zhangqw@jnu.edu.cn
Received Date: 03 August 2024
Accepted Date: 29 October 2024
Available online: 06 November 2024

Abstract

Human adenoviruses (HAdVs) are highly contagious pathogens with various genotypes implicated in acute respiratory disease (ARD) and linked to fatality, especially in immunosuppressed patients, young children, and military recruits. Currently, no vaccines or specific drugs are approved for clinical use. The hosts of adenoviruses are strictly species-specific, which strongly limits the development of vaccines and drugs against HAdVs. In this study, immunocompetent BALB/c mice were challenged with different doses of human adenovirus type 5 (HAdV-5) via tail intravenous injection (i.v.). All mice challenged with a high dose of HAdV-5 (3.2 × 10¹⁰ TCID₅₀/kg) died within 3–5 days, while those receiving a low dose of HAdV-5 (8 × 10⁹ or 4 × 10⁹ TCID₅₀/kg) survived. Interestingly, among the mice receiving a medium dose of HAdV-5 (1.6 × 10¹⁰ TCID₅₀/kg), 60% (n = 3/5) of male mice died, while all female mice survived. This suggests that male mice may be more susceptible to HAdV-5 infection than female mice, consistent with clinical findings in children. HAdV-5 DNA was mainly distributed in the liver, followed by the spleen and lung. Pathological changes were observed in the lung, liver, and spleen, with severity increasing in correlation with the virus challenge dosage. Transcriptome and qPCR analyses of the liver indicated that the down-regulated expression of the H2-Aa, H2-Ea-ps, CD74, and H2-Eb1 genes in male mice, as well as the AHR gene in female mice, may contribute to the observed higher mortality rates in male mice. Therefore, this effective, feasible, and cost-efficient mouse model could serve as a candidate for evaluating HAdV vaccines and anti-adenovirus therapeutics.
- Human adenovirus type 5 (HAdV-5)
- , Animal model
- , BALB/c mice
- , Severe human adenovirus infections

Electronic Supplementary Material

10.1016j.virs.2024.11.001-ESM2.xlsx

10.1016j.virs.2024.11.001-ESM1.docx
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