RSV infection of humanized lung-only mice induces pathological changes resembling severe bronchiolitis and bronchopneumonia.

Autor:	De C; International Center for the Advancement of Translational Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Pickles RJ; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Marsico Lung Institute, University of North Carolina, Chapel Hill, NC, USA., Yao W; International Center for the Advancement of Translational Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Liao B; International Center for the Advancement of Translational Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China., Boone A; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Marsico Lung Institute, University of North Carolina, Chapel Hill, NC, USA., Cleary RA; International Center for the Advancement of Translational Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Garcia JV; International Center for the Advancement of Translational Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA., Wahl A; International Center for the Advancement of Translational Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA.
Jazyk:	angličtina
Zdroj:	Frontiers in virology (Lausanne, Switzerland) [Front Virol] 2024; Vol. 4. Date of Electronic Publication: 2024 May 07.
DOI:	10.3389/fviro.2024.1380030
Abstrakt:	Respiratory syncytial virus (RSV) is a substantial cause of severe lower respiratory tract infections in infants, young children, older adults, and immunocompromised individuals. There is a vital need for effective therapeutics to prevent and/or treat severe RSV infection in these high-risk individuals. The development and pre-clinical testing of candidate RSV therapeutics could be accelerated by their evaluation in animals models that recapitulate bronchiolitis and bronchopneumonia; both hallmark features of severe RSV infection of humans. Previously, we demonstrated that implanted human lung tissue in humanized lung-only mice (LoM) can be infected with RSV resulting in a sustained virus replication. Here, we analyzed RSV-associated human lung pathology in the human lung implants of RSV-infected LoM. RSV infected epithelial cells lining the airway and alveolar regions of human lung implants resulting in hallmark histological features of RSV bronchiolitis and bronchopneumonia including distal airway and alveolar lumens clogged with 1) sloughed and necrotic RSV-infected epithelial cells, 2) neutrophil-containing inflammatory infiltrates, and 3) MUC5B dominated mucus secretions. We also show that treatment of LoM with a small molecule antiviral (ribavirin) or a neutralizing antibody (palivizumab) significantly suppressed and/or prevented RSV infection in vivo. Together, our data show that RSV infection of human lung implants in vivo has appropriate cellular tropism and results in hallmark pathological characteristics of severe bronchiolitis and bronchopneumonia in humans. They also offer proof-of-principle of the utility of this model to evaluate novel approaches for the prevention/treatment of RSV infection. Competing Interests: Conflict of interest statement: All authors declare they have no competing interests.
Databáze:	MEDLINE
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