Evidence of Mpox clade IIb infection in primary human alveolar epithelium
Issued Date
2025-01-01
Resource Type
eISSN
22221751
Scopus ID
2-s2.0-105000844514
Pubmed ID
40059759
Journal Title
Emerging Microbes and Infections
Volume
14
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Emerging Microbes and Infections Vol.14 No.1 (2025)
Suggested Citation
Namporn T., Manopwisedjaroen S., Ngodngamthaweesuk M., Pasomsub E., Jiravejchakul N., Saengfak R., Nealiga M.J., sea-be A., Basu A., Naruphontjirakul P., Hongeng S., Tetley T.D., Thitithanyanont A., Ruenraroengsak P. Evidence of Mpox clade IIb infection in primary human alveolar epithelium. Emerging Microbes and Infections Vol.14 No.1 (2025). doi:10.1080/22221751.2025.2477845 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/108606
Title
Evidence of Mpox clade IIb infection in primary human alveolar epithelium
Corresponding Author(s)
Other Contributor(s)
Abstract
Monkeypox virus (Mpox) has been recognized for causing distinct skin lesions and is primarily transmitted through skin and sexual contact. To date, the transmissibility and pathogenesis of the Mpox virus in distal human lung has never been completely explored. Here the transmission pathways and Mpox tropism on patient-derived air-liquid epithelium (ALE) model fabricated using isolated primary human alveolar epithelial cells (hAECs) were investigated. hAECs were cultured and exposed to the Mpox virus clade IIb isolated from the patient. DNA, proteins, and the tropism were elucidated using polymerase chain reaction (PCR), Western blot, and high-content fluorescent imaging. Transmission electron microscopy (TEM) was employed to systematically observe the cellular distribution of viral particles. Viral titres were determined by TCID50 assay. Innate immune response and inflammatory mediators were measured using Milliplex® multiplex and ELISA analysis. Pathology at alveolar barrier integrity was determined using transepithelial electrical resistance (TEER) analysis. The study included mock-infected cells as control. Mpox virus significantly infected 42.82% of total hAEC populations. The prominent observed pathology included a significant reduction in TEER values, loss of tight junction protein, presence of tunnelling nanotubes (TNTs), and syncytium morphology. Four stages of Mpox biogenesis were clearly observed without significant activation of IL-6, MIP1alpha, TNF-α, and Galectin-9, although IL-1β were subtly promoted. The developed patient-derived ALE is a versatile model for Mpox virus clade IIb infection reflecting respiratory transmission competence of the Mpox. Postinfection lung pathogenesis demonstrated alveolar barrier damage without significant inflammation, raising concerns about possible immune evasion by the virus.