title: Characterization of Nipah virus infection in a model of human airway epithelial cells cultured at an air-liquid interface.
abstract: Nipah virus (NiV) is an emerging paramyxovirus that can cause lethal respiratory illness in humans. No vaccine/therapeutic is currently licensed for humans. Human-to-human transmission was previously reported during outbreaks and NiV could be isolated from respiratory secretions, but the proportion of cases in Malaysia exhibiting respiratory symptoms was significantly lower than that in Bangladesh. Previously, we showed that primary human basal respiratory epithelial cells are susceptible to both NiV-Malaysia (M) and -Bangladesh (B) strains causing robust pro-inflammatory responses. However, the cells of the human respiratory epithelium that NiV targets are unknown and their role in NiV transmission and NiV-related lung pathogenesis is still poorly understood. Here, we characterized NiV infection of the human respiratory epithelium using a model of the human tracheal/bronchial (B-ALI) and small airway (S-ALI) epithelium cultured at an air-liquid interface. We show that NiV-M and NiV-B infect ciliated and secretory cells in B/S-ALI, and that infection of S-ALI, but not B-ALI, results in disruption of the epithelium integrity and host responses recruiting human immune cells. Interestingly, NiV-B replicated more efficiently in B-ALI than did NiV-M. These results suggest that the human tracheal/bronchial epithelium is favourable to NiV replication and shedding, while inducing a limited host response. Our data suggest that the small airways epithelium is prone to inflammation and lesions as well as constituting a point of virus entry into the pulmonary vasculature. The use of relevant models of the human respiratory tract, such as B/S-ALI, is critical for understanding NiV-related lung pathogenesis and identifying the underlying mechanisms allowing human-to-human transmission.
authors.affiliation: Department of Pathology at University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Olivier
authors.initials: O
authors.lastname: Escaffre
authors.affiliation: Department of Pathology at University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Viktoriya
authors.initials: V
authors.lastname: Borisevich
authors.affiliation: Center for Biomedical Engineering at University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Leoncio A
authors.initials: LA
authors.lastname: Vergara
authors.affiliation: Department of Pathology at University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Julie W
authors.initials: JW
authors.lastname: Wen
authors.affiliation: Rocky Mountain Veterinary Branch, Microscopy Unit, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Long
authors.affiliation: Department of Rare and Emerging Viral Infections and Response (EID), Centre for Infectious Disease Control (CIb), National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands.|Department of Pathology at University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Rockx
mesh_terms: D018929:Cell Culture Techniques; D002478:Cells, Cultured; D002923:Cilia; D004847:Epithelial Cells / Q000821:virology*; D006801:Humans; D045405:Nipah Virus / Q000145:classification / Q000502:physiology*; D020545:Respiratory Mucosa / Q000166:cytology*; D014779:Virus Replication / Q000502:physiology