Human CD46 humanized mice reveal interferon associated pulmonary immune remodeling during human adenovirus type 7 lung infection
4 affiliations
- 1Department of Respiratory Medicine, Children’s Hospital of Chongqing Medical University
- 2National Clinical Research Center for Children and Adolescents' Health and Diseases, Children's Hospital of Chongqing Medical University
- 3Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University
- 4Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children's Hospital of Chongqing Medical University
Abstract
Background: Human adenovirus type 7(HAdV-7) is a major cause of severe pediatric pneumonia, but the mechanisms linking viral infection to pulmonary immune remodeling and lung pathology remain incompletely understood. Progress has been limited by the lack of physiologically relevant animal models that recapitulate human susceptibility.
Methods: We generated human CD46 (hCD46) humanized mice and evaluated pulmonary viral burden, recoverable infectious virus, and lung pathology after HAdV-7 infection. Single-cell RNA sequencing was performed on lung tissues from wild type and hCD46 humanized mice under control and infected conditions to characterize cellular composition, transcriptional states, and intercellular communication. Human PBMC bulk transcriptomes from pediatric HAdV infection were further analyzed to assess the systemic relevance of mouse lung derived immune programs.
Results: hCD46 humanized mice showed increased pulmonary viral burden, recoverable infectious virions, and more severe lung pathology after HAdV-7 infection. Single-cell profiling revealed depletion of resident alveolar macrophages, pronounced expansion of inflammatory macrophage subsets, and remodeling of lymphoid transcriptional states in infected hCD46 lungs. These changes were accompanied by prominent type I/II interferon and interferon associated chemokine programs. B cells and CD4 ⁺ and CD8 ⁺ T cells showed prominent interferon stimulated genes (ISGs) associated transcriptional states, together with alterations in selected effector- and memory-associated programs and computationally inferred trajectories. Projection of mouse lung derived signatures onto transcriptomes of human peripheral blood mononuclear cell showed that selected interferon associated myeloid and lymphoid programs were also detectable systemically in pediatric HAdV infection.
Conclusions: HAdV-7 infection in hCD46 humanized mice was associated with an interferon enriched pulmonary inflammatory environment, prominent inflammatory myeloid remodeling, and altered lymphoid transcriptional states. This susceptible mouse model provides a useful experimental tool for studying HAdV-7 associated lung disease and for preclinical evaluation of antiviral, immunomodulatory, and vaccine strategies.
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BibTeX
@article{yang2026human,
title = {{Human CD46 humanized mice reveal interferon associated pulmonary immune remodeling during human adenovirus type 7 lung infection}},
author = {Zhongying Yang and Zijun Meng and Mingling Wan and Ying Lu and Lifen Rao and Hui Qu and Jianhua Wei and Jing Liao and Enmei Liu and Na Zang},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1919716},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1919716/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Human CD46 humanized mice reveal interferon associated pulmonary immune remodeling during human adenovirus type 7 lung infection
AU - Zhongying Yang
AU - Zijun Meng
AU - Mingling Wan
AU - Ying Lu
AU - Lifen Rao
AU - Hui Qu
AU - Jianhua Wei
AU - Jing Liao
AU - Enmei Liu
AU - Na Zang
PY - 2026
DA - 2026/10/13
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1919716
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1919716/full
AB - Background: Human adenovirus type 7(HAdV-7) is a major cause of severe pediatric pneumonia, but the mechanisms linking viral infection to pulmonary immune remodeling and lung pathology remain incompletely understood. Progress has been limited by the lack of physiologically relevant animal models that recapitulate human susceptibility. Methods: We generated human CD46 (hCD46) humanized mice and evaluated pulmonary viral burden, recoverable infectious virus, and lung pathology after HAdV-7 infection. Single-cell RNA sequencing was performed on lung tissues from wild type and hCD46 humanized mice under control and infected conditions to characterize cellular composition, transcriptional states, and intercellular communication. Human PBMC bulk transcriptomes from pediatric HAdV infection were further analyzed to assess the systemic relevance of mouse lung derived immune programs. Results: hCD46 humanized mice showed increased pulmonary viral burden, recoverable infectious virions, and more severe lung pathology after HAdV-7 infection. Single-cell profiling revealed depletion of resident alveolar macrophages, pronounced expansion of inflammatory macrophage subsets, and remodeling of lymphoid transcriptional states in infected hCD46 lungs. These changes were accompanied by prominent type I/II interferon and interferon associated chemokine programs. B cells and CD4 ⁺ and CD8 ⁺ T cells showed prominent interferon stimulated genes (ISGs) associated transcriptional states, together with alterations in selected effector- and memory-associated programs and computationally inferred trajectories. Projection of mouse lung derived signatures onto transcriptomes of human peripheral blood mononuclear cell showed that selected interferon associated myeloid and lymphoid programs were also detectable systemically in pediatric HAdV infection. Conclusions: HAdV-7 infection in hCD46 humanized mice was associated with an interferon enriched pulmonary inflammatory environment, prominent inflammatory myeloid remodeling, and altered lymphoid transcriptional states. This susceptible mouse model provides a useful experimental tool for studying HAdV-7 associated lung disease and for preclinical evaluation of antiviral, immunomodulatory, and vaccine strategies.
SN - 1664-3224
ER -