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Risk assessment of the tropism & pathogenesis of the highly pathogenic avian influenza A/H7N9 virus using ex vivo & in vitro cultures of human respiratory tract

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  • Risk assessment of the tropism & pathogenesis of the highly pathogenic avian influenza A/H7N9 virus using ex vivo & in vitro cultures of human respiratory tract

    J Infect Dis. 2019 Apr 18. pii: jiz165. doi: 10.1093/infdis/jiz165. [Epub ahead of print]
    Risk assessment of the tropism & pathogenesis of the highly pathogenic avian influenza A/H7N9 virus using ex vivo & in vitro cultures of human respiratory tract.

    Chan LLY1, Hui KPY1, Kuok DIT1, Bui CHT1, Ng KC1, Mok CKP2,3, Yang ZF3,4, Guan W3, Poon LLM1, Zhong N3, Peiris JSM1, Nicholls JM5, Chan MCW1.
    Author information

    Abstract

    Highly pathogenic avian influenza (HPAI)-H7N9 virus arising from low pathogenic avian influenza (LPAI)-H7N9 virus with polybasic amino acid substitutions in the haemagglutinin was detected in 2017. We compared the tropism, replication competence and cytokine induction of HPAI-H7N9, LPAI-H7N9 and HPAI-H5N1 in ex vivo human respiratory tract explants and in vitro culture of human alveolar epithelial cells (AECs) and pulmonary microvascular endothelial cells (HMVEC-L). Replication competence of HPAI- and LPAI-H7N9 were comparable in ex vivo cultures of bronchus and lung. HPAI-H7N9 predominantly infected AECs, while 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 implying that endothelial tropism may involve in pathogenesis of HPAI-H7N9 disease.
    The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.


    KEYWORDS:

    H5N1; H7N9; HPAI; Risk assessment; alveolar epithelial cells; ex vivo; influenza; pathogenesis; pulmonary microvascular endothelial cells; tropism

    PMID: 31001638 DOI: 10.1093/infdis/jiz165
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