Maxence Frétaud1, Delphyne Descamps1, Daphné Laubreton1,2, Marie-Anne Rameix-Welti3,4, Jean-François Eléouët1, Thibaut Larcher5, Marie Galloux1, Christelle Langevin1,6. 1. Université Paris-Saclay, INRAE, UVSQ, VIM, 78350 Jouy-en-Josas, France. 2. CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007 Lyon, France. 3. Université Paris-Saclay, INSERM, Université de Versailles St. Quentin, UMR 1173 (2I), 78000 Versailles, France. 4. Assistance Publique Hôpitaux de Paris, Université Paris Saclay, Hôpital Ambroise Paré, Laboratoire de Microbiologie, 92100 Boulogne-Billancourt, France. 5. INRAE, Oniris, UMR 703 APEX, 44307 Nantes, France. 6. INRAE, IERP, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
Abstract
BACKGROUND: Respiratory Syncytial Virus (RSV) is the major cause of severe acute respiratory tract illness in young children worldwide and a main pathogen for the elderly and immune-compromised people. In the absence of vaccines or effective treatments, a better characterization of the pathogenesis of RSV infection is required. To date, the pathophysiology of the disease and its diagnosis has mostly relied on chest X-ray and genome detection in nasopharyngeal swabs. The development of new imaging approaches is instrumental to further the description of RSV spread, virus-host interactions and related acute respiratory disease, at the level of the entire lung. METHODS: By combining tissue clearing, 3D microscopy and image processing, we developed a novel visualization tool of RSV infection in undissected mouse lungs. RESULTS: Whole tissue analysis allowed the identification of infected cell subtypes, based on both morphological traits and position within the cellular network. Furthermore, 3D imaging was also valuable to detect the cytoplasmic viral factories, also called inclusion bodies, a hallmark of RSV infection. CONCLUSIONS: Whole lung clearing and 3D deep imaging represents an unprecedented visualization method of infected lungs to allow insight into RSV pathophysiology and improve the 2D histology analyses.
BACKGROUND:Respiratory Syncytial Virus (RSV) is the major cause of severe acute respiratory tract illness in young children worldwide and a main pathogen for the elderly and immune-compromised people. In the absence of vaccines or effective treatments, a better characterization of the pathogenesis of RSV infection is required. To date, the pathophysiology of the disease and its diagnosis has mostly relied on chest X-ray and genome detection in nasopharyngeal swabs. The development of new imaging approaches is instrumental to further the description of RSV spread, virus-host interactions and related acute respiratory disease, at the level of the entire lung. METHODS: By combining tissue clearing, 3D microscopy and image processing, we developed a novel visualization tool of RSV infection in undissected mouse lungs. RESULTS: Whole tissue analysis allowed the identification of infected cell subtypes, based on both morphological traits and position within the cellular network. Furthermore, 3D imaging was also valuable to detect the cytoplasmic viral factories, also called inclusion bodies, a hallmark of RSV infection. CONCLUSIONS: Whole lung clearing and 3D deep imaging represents an unprecedented visualization method of infected lungs to allow insight into RSV pathophysiology and improve the 2D histology analyses.
Entities:
Keywords:
3D imaging of lungs; RSV infection; RSV tropism; inclusion bodies; tissue clearing; viral pathophysiology
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