Tropism and innate host responses of a novel avian influenza A H7N9 virus: an analysis of ex-vivo and in-vitro cultures of the human respiratory tract (The Lancet Resp Med., abstract, edited) 2013

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2013 2013 2013 [Source: The Lancet Respiratory Medicine, full page: (<a href="http://www.thelancet.com/journals/lanres/article/PIIS2213-2600(13)70138-3/abstract">LINK</a>). Abstract, edited.] The Lancet Respiratory Medicine, Early Online Publication, 25 July 2013 doi:10.1016/S2213-2600(13)70138-3 Copyright © 2013 Elsevier Ltd All rights reserved. Tropism and innate host responses of a novel avian influenza A H7N9 virus: an analysis of ex-vivo and in-vitro cultures of the human respiratory tract Original Text Michael CW Chan PhD a †, Renee WY Chan PhD a †, Louisa LY Chan BSc a †, Chris KP Mok PhD a †, Kenrie PY Hui PhD a, Joanne HM Fong MSc a, Kin P Tao PhD a, Leo LM Poon DPhil a b, Prof John M Nicholls FRCPA c, Prof Y Guan PhD a b d, Prof JS Malik Peiris DPhil a b   Summary Background Since March, 2013, an avian-origin influenza A H7N9 virus has caused severe pneumonia in China. The aim of this study was to investigate the pathogenesis of this new virus in human beings. Methods We obtained ex-vivo cultures of the human bronchus, lung, nasopharynx, and tonsil and in-vitro cultures of primary human alveolar epithelial cells and peripheral blood monocyte-derived macrophages. We compared virus tropism and induction of proinflammatory cytokine responses of two human influenza A H7N9 virus isolates, A/Shanghai/1/2013 and A/Shanghai/2/2013; a highly pathogenic avian influenza H5N1 virus; the highly pathogenic avian influenza H7N7 virus that infected human beings in the Netherlands in 2003; the 2009 pandemic influenza H1N1 virus, and a low pathogenic duck H7N9 virus that was genetically different to the human disease causing A H7N9 viruses. Findings Both human H7N9 viruses replicated efficiently in human bronchus and lung ex-vivo cultures, whereas duck/H7N9 virus failed to replicate in either. Both human A H7N9 viruses infected both ciliated and non-ciliated human bronchial epithelial cells and replicated to higher titres than did H5N1 (p<0·0001 to 0·0046) and A/Shanghai/1/2013 replicated to higher titres than did H7N7 (p=0·0002—0·01). Both human A H7N9 viruses predominantly infected type II alveolar epithelial cells and alveolar macrophages in the human lung and replicated to higher titres than did H5N1 (p<0·0001 to 0·0078); A/Shanghai/1/2013 replicated to higher titres than did H1N1 (p=0·0052—0·05) and H7N7 (p=0·0031—0·0151). Human H7N9 viruses were less potent inducers of proinflammatory cytokines compared with H5N1 virus. Interpretation Collectively, the results suggest that the novel H7N9 viruses are better adapted to infect and replicate in the human conducting and lower airways than are other avian influenza viruses, including H5N1, and pose an important pandemic threat. Funding Area of Excellence Scheme of the University Grants Committee (AoE/M-12/96), Hong Kong Special Administrative Region. ______ a Centre of Influenza Research and School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China; b State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China; c Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong SAR, China; d Joint Influenza Research Centre (SUMC/HKU), Shantou University Medical College/Hong Kong University, Shantou, China Correspondence to: Prof J S Malik Peiris, Centre of Influenza Research, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China † Equal contributors - ------- 2013 2013 2013 [Source: The Lancet Respiratory Medicine, full page: (<a href="http://www.thelancet.com/journals/lanres/article/PIIS2213-2600(13)70138-3/abstract">LINK</a>). Abstract, edited.] The Lancet Respiratory Medicine, Early Online Publication, 25 July 2013 doi:10.1016/S2213-2600(13)70138-3 Copyright © 2013 Elsevier Ltd All rights reserved. Tropism and innate host responses of a novel avian influenza A H7N9 virus: an analysis of ex-vivo and in-vitro cultures of the human respiratory tract Original Text Michael CW Chan PhD a †, Renee WY Chan PhD a †, Louisa LY Chan BSc a †, Chris KP Mok PhD a †, Kenrie PY Hui PhD a, Joanne HM Fong MSc a, Kin P Tao PhD a, Leo LM Poon DPhil a b, Prof John M Nicholls FRCPA c, Prof Y Guan PhD a b d, Prof JS Malik Peiris DPhil a b   Summary Background Since March, 2013, an avian-origin influenza A H7N9 virus has caused severe pneumonia in China. The aim of this study was to investigate the pathogenesis of this new virus in human beings. Methods We obtained ex-vivo cultures of the human bronchus, lung, nasopharynx, and tonsil and in-vitro cultures of primary human alveolar epithelial cells and peripheral blood monocyte-derived macrophages. We compared virus tropism and induction of proinflammatory cytokine responses of two human influenza A H7N9 virus isolates, A/Shanghai/1/2013 and A/Shanghai/2/2013; a highly pathogenic avian influenza H5N1 virus; the highly pathogenic avian influenza H7N7 virus that infected human beings in the Netherlands in 2003; the 2009 pandemic influenza H1N1 virus, and a low pathogenic duck H7N9 virus that was genetically different to the human disease causing A H7N9 viruses. Findings Both human H7N9 viruses replicated efficiently in human bronchus and lung ex-vivo cultures, whereas duck/H7N9 virus failed to replicate in either. Both human A H7N9 viruses infected both ciliated and non-ciliated human bronchial epithelial cells and replicated to higher titres than did H5N1 (p<0·0001 to 0·0046) and A/Shanghai/1/2013 replicated to higher titres than did H7N7 (p=0·0002—0·01). Both human A H7N9 viruses predominantly infected type II alveolar epithelial cells and alveolar macrophages in the human lung and replicated to higher titres than did H5N1 (p<0·0001 to 0·0078); A/Shanghai/1/2013 replicated to higher titres than did H1N1 (p=0·0052—0·05) and H7N7 (p=0·0031—0·0151). Human H7N9 viruses were less potent inducers of proinflammatory cytokines compared with H5N1 virus. Interpretation Collectively, the results suggest that the novel H7N9 viruses are better adapted to infect and replicate in the human conducting and lower airways than are other avian influenza viruses, including H5N1, and pose an important pandemic threat. Funding Area of Excellence Scheme of the University Grants Committee (AoE/M-12/96), Hong Kong Special Administrative Region. ______ a Centre of Influenza Research and School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China; b State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China; c Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong SAR, China; d Joint Influenza Research Centre (SUMC/HKU), Shantou University Medical College/Hong Kong University, Shantou, China Correspondence to: Prof J S Malik Peiris, Centre of Influenza Research, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China † Equal contributors - ------- 2013 2013 2013 <a href="http://www.matrixar.com/" title="Matrix ">المصفوفة : أجمل الخلفيات والصور</a>