• Medientyp: E-Artikel
  • Titel: Risk Assessment of the Tropism and Pathogenesis of the Highly Pathogenic Avian Influenza A/H7N9 Virus Using Ex Vivo and In Vitro Cultures of Human Respiratory Tract
  • Beteiligte: Chan, Louisa L Y; Hui, Kenrie P Y; Kuok, Denise I T; Bui, Christine H T; Ng, Ka-chun; Mok, Chris K P; Yang, Zi-feng; Guan, Wenda; Poon, Leo L M; Zhong, Nanshan; Peiris, J S Malik; Nicholls, John M; Chan, Michael C W
  • Erschienen: Oxford University Press (OUP), 2019
  • Erschienen in: The Journal of Infectious Diseases, 220 (2019) 4, Seite 578-588
  • Sprache: Englisch
  • DOI: 10.1093/infdis/jiz165
  • ISSN: 0022-1899; 1537-6613
  • Schlagwörter: Infectious Diseases ; Immunology and Allergy
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  • Beschreibung: Abstract Background Highly pathogenic avian influenza (HPAI)-H7N9 virus arising from low pathogenic avian influenza (LPAI)-H7N9 virus with polybasic amino acid substitutions in the hemagglutinin was detected in 2017. Methods We compared the tropism, replication competence, and cytokine induction of HPAI-H7N9, LPAI-H7N9, and HPAI-H5N1 in ex vivo human respiratory tract explants, in vitro culture of human alveolar epithelial cells (AECs) and pulmonary microvascular endothelial cells (HMVEC-L). Results Replication competence of HPAI- and LPAI-H7N9 were comparable in ex vivo cultures of bronchus and lung. HPAI-H7N9 predominantly infected AECs, whereas limited infection was observed in bronchus. The reduced tropism of HPAI-H7N9 in bronchial epithelium may explain the lack of human-to-human transmission despite a number of mammalian adaptation markers. Apical and basolateral release of virus was observed only in HPAI-H7N9- and H5N1-infected AECs regardless of infection route. HPAI-H7N9, but not LPAI-H7N9 efficiently replicated in HMVEC-L. Conclusions Our findings demonstrate that a HPAI-H7N9 virus efficiently replicating in ex vivo cultures of human bronchus and lung. The HPAI-H7N9 was more efficient at replicating in human AECs and HMVEC-L than LPAI-H7N9 implying that endothelial tropism may involve in pathogenesis of HPAI-H7N9 disease.
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