DataVXAdvanced SciencePaper
journal article·2026-03Open access

A Lung‐Immune Dual‐Humanized Mouse Using Cryopreserved Tissue Enables Infection and Immune Profiling of Human Common Cold Coronaviruses

Chunyu Cheng, Jing Sun, Chun Lu, Qian Yu, Yiyun He, Bingqing Wu, Deshan Ren, Shuai Ding, Jincun Zhao, Yan Li

Advanced Science· Volume 13· Issue 16
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Source abstract

Abstract

Abstract Human common cold coronaviruses (CCCoVs, e.g., 229E, NL63, OC43, HKU1) hold critical yet underexplored significance in understanding coronavirus evolutionary dynamics and immune cross‐protection, offering insights for predicting emerging pathogens and developing pan‐coronavirus vaccines. However, research is hindered by the lack of animal models due to strict human‐specific tropism and the confounding effects of frequent co‐infections from clinical samples, which obscure virus‐specific pathogenesis. Although lung‐humanized mice have been used in SARS‐CoV‐2 studies, their application to CCCoVs remains unvalidated and relies on logistically challenging fresh human tissues. This study optimizes a transplantation strategy using cryopreserved human fetal lung tissue, achieving enhanced engraftment efficiency. And the refined model supports robust infection by all four major CCCoVs and demonstrates the therapeutic efficacy of Paxlovid against HKU1. Furthermore, comparative analysis reveals phenotypic distinctions in human immune cells between native mouse lungs and human lung implants in lung‐immune dual‐humanized mice. The model also enables validation of virus‐specific T cell responses and assessment of SARS‐CoV‐2 cross‐reactivity post‐HKU1 infection. Overall, this study establishes a scalable platform using cryopreserved tissues for respiratory virus research, overcoming prior limitations in modeling human‐specific tropism and dissecting immune‐pathogen interactions.
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Research context

Biomaterials

OpenAlex topics: SARS-CoV-2 and COVID-19 Research · Virus-based gene therapy research · Tissue Engineering and Regenerative Medicine

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

MOE Key Laboratory of Model Animal for Disease Study Model Animal Research Center Department of Oncology Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University Nanjing 210093 China

State Key Laboratory of Respiratory Disease National Clinical Research Centre for Respiratory Disease National Centre for Respiratory Medicine Guangzhou Institute of Respiratory Health the First Affiliated Hospital of Guangzhou Medical University Guangzhou Medical University Guangzhou Guangdong 510182 China

School of Basic Medical Sciences Guangzhou Medical University Guangzhou Guangdong 510182 China

Department of Rheumatology and Immunology Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School Nanjing 210008 China

Guangzhou National Laboratory Guangzhou International Bio Island Guangzhou Guangdong 510005 China

Shanghai Institute for Advanced Immunochemical Studies School of Life Science and Technology Shanghai Tech University Shanghai 201210 China

Chemistry and Biomedicine Innovation Center (ChemBIC) ChemBioMed Interdisciplinary Research Center Nanjing University Nanjing 210093 China

Wuxi Xishan NJU Institute of Applied Biotechnology Wuxi 214000 China

Funding

Fundamental Research Funds for the Central Universities · National Natural Science Foundation of China · Basic and Applied Basic Research Foundation of Guangdong Province · Ministry of Science and Technology of the People's Republic of China

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