Authentic Modeling of Human Respiratory Virus Infection in Human Pluripotent Stem Cell-Derived Lung Organoids

Author:

Porotto M.123,Ferren M.12,Chen Y.-W.4567,Siu Y.128,Makhsous N.910,Rima B.11,Briese T.1213,Greninger A. L.910,Snoeck H.-W.4568,Moscona A.12814

Affiliation:

1. Department of Pediatrics, Columbia University Medical Center, New York, New York, USA

2. Center for Host-Pathogen Interaction, Columbia University Medical Center, New York, New York, USA

3. Department of Experimental Medicine, University of Campania, Caserta, Italy

4. Columbia Center for Human Development, Columbia University Medical Center, New York, New York, USA

5. Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA

6. Department of Medicine, Columbia University Medical Center, New York, New York, USA

7. Hastings Center for Pulmonary Research and Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA

8. Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, USA

9. Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA

10. Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

11. Center for Experimental Medicine, Queen's University, Belfast, Northern Ireland, United Kingdom

12. Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, USA

13. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA

14. Department of Physiology & Cellular Biophysics, Columbia University Medical Center, New York, New York, USA

Abstract

Respiratory viruses are among the first pathogens encountered by young children, and the significant impact of these viral infections on the developing lung is poorly understood. Circulating viruses are suited to the environment of the human lung and are different from those of viruses grown in cultured cells. We modeled respiratory virus infections that occur in children or infect the distal lung using lung organoids that represent the entire developing infant lung. These 3D lung organoids, derived from human pluripotent stem cells, develop into branching airway and alveolar structures and provide a tissue environment that maintains the authentic viral genome. The lung organoids can be genetically engineered prior to differentiation, thereby generating tissues bearing or lacking specific features that may be relevant to viral infection, a feature that may have utility for the study of host-pathogen interaction for a range of lung pathogens.

Funder

HHS | National Institutes of Health

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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