| Author | Vaswani, Chirag M. | |
| Author | Varkouhi, Amir K. | |
| Author | Gupta, Sahil | |
| Author | Ektesabi, Amin M. | |
| Author | Tsoporis, James N. | |
| Author | Yousef, Sadiya | |
| Author | Plant, Pamela J. | |
| Author | Silva, Adriana L. da | |
| Author | Cen, Yuchen | |
| Author | Tseng, Yi-Chieh | |
| Author | Batah, Sabrina S. | |
| Author | Fabro, Alexandre T. | |
| Author | Advani, Suzanne L. | |
| Author | Advani, Andrew | |
| Author | Leong-Poi, Howard | |
| Author | Marshall, John C. | |
| Author | Garcia, Cristiana C. | |
| Author | Rocco, Patricia R.M. | |
| Author | Albaiceta, Guillermo M. | |
| Author | Sebastian-Bolz, Steffen | |
| Author | Watts, Tania H. | |
| Author | Moraes, Theo J. | |
| Author | Capelozzi, Vera L. | |
| Author | Santos, Claudia. C. dos | |
| Access date | 2023-07-18T16:51:07Z | |
| Available date | 2023-07-18T16:51:07Z | |
| Document date | 2023 | |
| Citation | VASWANI, Chirag M. et al. Preventing occludin tight-junction disruption via inhibition of microRNA-193b-5p attenuates viral load and influenza-induced lung injury. Molecular Therapy, v. 31, n. 8, 2023. doi.org/10.1016/j.ymthe.2023.06.011 | en_US |
| ISSN | 1525-0016 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/59659 | |
| Language | eng | en_US |
| Publisher | Cell Press | en_US |
| Rights | open access | en_US |
| Title | Preventing occludin tight-junction disruption via inhibition of microRNA-193b-5p attenuates viral load and influenza-induced lung injury. | en_US |
| Type | Article | en_US |
| Abstract | Virus-induced lung injury is associated with loss of pulmonary epithelial-endothelial tight junction integrity. While the alveolar-capillary membrane may be an indirect target of injury, viruses may interact directly and/or indirectly with miRs to augment their replication potential and evade the host antiviral defense system. Here, we expose how the influenza virus (H1N1) capitalizes on host-derived interferon-induced, microRNA (miR)-193b-5p to target occludin and compromise antiviral defenses. Lung biopsies from patients infected with H1N1 revealed increased miR-193b-5p levels, marked reduction in occludin protein, and disruption of the alveolar-capillary barrier. In C57BL/6 mice, the expression of miR-193b-5p increased, and occludin decreased, 5–6 days post-infection with influenza (PR8). Inhibition of miR-193b-5p in primary human bronchial, pulmonary microvascular, and nasal epithelial cells enhanced antiviral responses. miR-193b-deficient mice were resistant to PR8. Knockdown of occludin, both in vitro and in vivo, and overexpression of miR-193b-5p reconstituted susceptibility to viral infection. miR-193b-5p inhibitor mitigated loss of occludin, improved viral clearance, reduced lung edema, and augmented survival in infected mice. Our results elucidate how the innate immune system may be exploited by the influenza virus and how strategies that prevent loss of occludin and preserve tight junction function may limit susceptibility to virus-induced lung injury. | en_US |
| Affilliation | Department of Physiology. Temerty Faculty of Medicine. University of Toronto. Toronto, ON, Canada/Keenan Research Centre for Biomedical Science. St. Michael’s Hospital. Toronto, ON, Canada | en_US |
| Affilliation | Department of Chemistry and Environmental Science. New Jersey Institute of Technology. Newark, NJ, USA | en_US |
| Affilliation | Keenan Research Centre for Biomedical Science. St. Michael’s Hospital. Toronto, ON, Canada/Institute of Medical Sciences. Faculty of Medicine. University of Toronto. Toronto, ON, Canada/Faculty of Medicine. School of Medicine. The University of Queensland. Herston, Australia | en_US |
| Affilliation | Keenan Research Centre for Biomedical Science. St. Michael’s Hospital. Toronto, ON, Canada/Institute of Medical Sciences. Faculty of Medicine. University of Toronto. Toronto, ON, Canada | en_US |
| Affilliation | Keenan Research Centre for Biomedical Science. St. Michael’s Hospital. Toronto, ON, Canada | en_US |
| Affilliation | Keenan Research Centre for Biomedical Science. St. Michael’s Hospital. Toronto, ON, Canada | en_US |
| Affilliation | Keenan Research Centre for Biomedical Science. St. Michael’s Hospital. Toronto, ON, Canada | en_US |
| Affilliation | Laboratory of Pulmonary Investigation. Carlos Chagas Filho Institute of Biophysics. Federal University of Rio de Janeiro. Rio de Janeiro, RJ, Brazil/COVID-19 Virus Network from Ministry of Science, Technology, and Innovation. Brazilian Council for Scientific and Technological Development. Foundation Carlos Chagas Filho Research Support of the State of Rio de Janeiro. Rio de Janeiro, RJ, Brazil | en_US |
| Affilliation | Program in Translational Medicine. SickKids Research Institute. Toronto, ON, Canada | en_US |
| Affilliation | Program in Translational Medicine. SickKids Research Institute. Toronto, ON, Canada | en_US |
| Affilliation | Department of Pathology and Legal Medicine. Ribeirão Preto Medical School. University of São Paulo. São Paulo, SP, Brazil | en_US |
| Affilliation | Department of Pathology and Legal Medicine. Ribeirão Preto Medical School. University of São Paulo. São Paulo, SP, Brazil | en_US |
| Affilliation | Keenan Research Centre for Biomedical Science. St. Michael’s Hospital. Toronto, ON, Canada | en_US |
| Affilliation | Keenan Research Centre for Biomedical Science. St. Michael’s Hospital. Toronto, ON, Canada | en_US |
| Affilliation | Keenan Research Centre for Biomedical Science. St. Michael’s Hospital. Toronto, ON, Canada/Institute of Medical Sciences. Faculty of Medicine. University of Toronto. Toronto, ON, Canada | en_US |
| Affilliation | Keenan Research Centre for Biomedical Science. St. Michael’s Hospital. Toronto, ON, Canada/Institute of Medical Sciences. Faculty of Medicine. University of Toronto. Toronto, ON, Canada | en_US |
| Affilliation | Laboratory of Respiratory. Exanthematic Viruses, Enterovirus and Viral Emergencies. Oswaldo Cruz Institute. Oswaldo Cruz Foundation. Rio de Janeiro, RJ, Brazil/Integrated Research Group on Biomarkers. René Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil | en_US |
| Affilliation | Laboratory of Pulmonary Investigation. Carlos Chagas Filho Institute of Biophysics. Federal University of Rio de Janeiro. Rio de Janeiro, RJ, Brazil/COVID-19 Virus Network from Ministry of Science, Technology, and Innovation. Brazilian Council for Scientific and Technological Development. Foundation Carlos Chagas Filho Research Support of the State of Rio de Janeiro. Rio de Janeiro, RJ, Brazil | en_US |
| Affilliation | Departamento de Biología Funcional. Instituto Universitario de Oncología del Principado de Asturias. Universidad de Oviedo. Oviedo, Spain/Unidad de Cuidados Intensivos Cardiológicos. Hospital Universitario Central de Asturias. Oviedo, Spain/CIBER-Enfermedades Respiratorias. Instituto de Salud Carlos III. Madrid, Spain | en_US |
| Affilliation | Department of Physiology. Temerty Faculty of Medicine. University of Toronto. Toronto, ON, Canada | en_US |
| Affilliation | Department of Immunology. Temerty Faculty of Medicine. University of Toronto. Toronto, ON, Canada | en_US |
| Affilliation | Program in Translational Medicine. SickKids Research Institute. Toronto, ON, Canada/Department of Pediatrics University of Toronto and Respirology. Hospital for Sick Children. Toronto, ON, Canada | en_US |
| Affilliation | Department of Pathology. University of São Paulo. São Paulo, SP, Brazil | en_US |
| Affilliation | Department of Physiology. Temerty Faculty of Medicine. University of Toronto. Toronto, ON, Canad/ Keenan Research Centre for Biomedical Science. St. Michael’s Hospital. Toronto, ON, Canada/Institute of Medical Sciences. Faculty of Medicine. University of Toronto. Toronto, ON, Canada/Laboratory Medicine and Pathobiology. Faculty of Medicine. University of Toronto. Toronto, ON, Canada/Interdepartmental Division of Critical Care. St Michael’s Hospital. University of Toronto. Toronto, ON, Canada | en_US |
| Subject | acute respiratory distress syndrome | en_US |
| Subject | acute lung injury | en_US |
| Subject | influenza virus | en_US |
| Subject | tight junctions | en_US |
| Subject | occludin | en_US |
| Subject | microRNA | en_US |
| Subject | miR-193b | en_US |
| Subject | interferon beta | en_US |
| Subject | alveolar-capillary membrane | en_US |
| Subject | antiviral immune response | en_US |
