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Open AccessArticle

Infection of Human Tracheal Epithelial Cells by H5 Avian Influenza Virus Is Regulated by the Acid Stability of Hemagglutinin and the pH of Target Cell Endosomes

1
Department of Infectious Diseases, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
2
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Current affiliations: Laboratory of Ultrastructural Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
Viruses 2020, 12(1), 82; https://doi.org/10.3390/v12010082
Received: 24 December 2019 / Revised: 4 January 2020 / Accepted: 5 January 2020 / Published: 9 January 2020
(This article belongs to the Special Issue Evolution and Pathogenesis of Avian and Animal Influenza Viruses)
Despite the possible relationships between tracheal infection and concomitant infection of the terminal part of the lower respiratory tract (bronchioles/alveoli), the behavior of avian influenza viruses (AIVs), such as H5N1, in the conducting airways is unclear. To examine the tropism of AIVs for cells lining the conducting airways of humans, we established human tracheal epithelial cell clones (HTEpC-Ts) and examined their susceptibility to infection by AIVs. The HTEpC-Ts showed differing susceptibility to H5N1 and non-zoonotic AIVs. Viral receptors expressed by HTEpC-Ts bound all viruses; however, the endosomal pH was associated with the overall susceptibility to infection by AIVs. Moreover, H5N1 hemagglutinin broadened viral tropism to include HTEpC-Ts, because it had a higher pH threshold for viral–cell membrane fusion. Thus, H5N1 viruses infect human tracheal epithelial cells as a result of their higher pH threshold for membrane fusion which may be one mechanism underlying H5N1 pathogenesis in human airway epithelia. Efficient replication of H5N1 in the conducting airways of humans may facilitate infection of the lower respiratory tract. View Full-Text
Keywords: avian influenza virus; tracheal epithelial cells; hemagglutinin; endosomal pH avian influenza virus; tracheal epithelial cells; hemagglutinin; endosomal pH
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MDPI and ACS Style

Daidoji, T.; Kajikawa, J.; Arai, Y.; Watanabe, Y.; Hirose, R.; Nakaya, T. Infection of Human Tracheal Epithelial Cells by H5 Avian Influenza Virus Is Regulated by the Acid Stability of Hemagglutinin and the pH of Target Cell Endosomes. Viruses 2020, 12, 82.

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