Palermo1, L.M., Porotto1, M., Yokoyama1, C.C., Palmer1, S.G., Mungall1,2, B.A., Greengard1,4, O., Niewiesk3, S., Moscona1, A. 1Department of Pediatrics and of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021. 2Australian Animal Health Laboratory, CSIRO Livestock Industries, 5 Portarlington Road, Geelong, Australia 3220. 3Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210. 4Department of Pediatrics, Mount Sinai Hospital, NY.

This study by researchers at Weill Medical College of Cornell University, the Australian Animal Health Laboratory/CSIRO, Ohio State University College of Veterinary Medicine and Mount Sinai Hospital demonstrated that MatTek’s EpiAirway in vitro human tracheal/bronchial tissue equivalent provides an ideal system for assessing the interplay of host cell and viral factors in pathogenesis (human parainfluenza virus infection of airway epithelium), and for screening for inhibitory molecules that would be effective in vivo. Three discrete activities of the paramyxovirus hemagglutinin-neuraminidase (HN) protein — receptor binding, receptor cleaving (neuraminidase), and triggering of the fusion protein — each affect the promotion of viral fusion and entry. For human parainfluenza virus 3 (HPIV3), the effects of specific mutations that alter these functions of the receptor-binding protein have been well-characterized in cultured monolayer cells, and have identified steps potentially relevant to pathogenesis. In the present study, proposed mechanisms relevant to pathogenesis were tested in natural host cell cultures — a model of the human airway epithelium (EpiAirway™, MatTek Corp.) in which primary human airway epithelium are cultured at an air-liquid interface and retain functional properties. Infection of human airway epithelium with wt HPIV3 and variant viruses closely reflects that seen in an animal model, the cotton rat, suggesting that human airway epithelium provide an ideal system for assessing the interplay of host cell and viral factors in pathogenesis, and for screening for inhibitory molecules that would be effective in vivo. Both the HN’s receptor avidity, and the function and timing of F-activation by HN, require a critical balance for establishment of ongoing infection in the human airway epithelium, and these HN functions independently modulate production of active virions. Alterations in HN’s F-triggering function lead to release of non-infectious viral particles, and failure of virus to spread. The finding that dysregulation of F-triggering prohibits successful infection in human airway epithelium suggests that antiviral strategies targeted to HN’s F-triggering activity may have promise in vivo.


AIR-100, EpiAirway, F-activation, F-triggering, Flu virus, Fusion protein activation, HPIV3, Hemagglutinin-neuraminidase, Human parainfluenza virus, Inhibitory molecules, Neuraminidase, Paramyxovirus hemagglutinin-neuraminidase, Pathogenesis, Receptor avidity, Receptor binding, Receptor binding protein, Receptor cleaving, Viral collection, Viral infection, Viral pathogenesis, Viral shedding

Materials Tested

C. Perfiringens neuraminidase, Human parainfluenza 3 (HPIV3), Zanamivir

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