The Lancet Resp Med. 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

[Giuseppe]

[Source: The Lancet Respiratory Medicine, full page: (LINK). 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.
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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


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[sharon sanders]

Re: The Lancet Resp Med. 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

Press Releases



July 25, 2013



HKU?s finding on avian influenza A (H7N9) virus well adapted to infect human respiratory tract reveals why numerous human infected cases in a short period of time
HKU research team reveals why the avian influenza (H7N9) virus led to over 130 human cases in a relatively short period of time. By using human respiratory tract tissues maintained in culture, the researchers discover that the avian influenza A (H7N9) virus is as efficient as the 2009 pandemic H1N1 virus, commonly known as swine influenza, in infecting the human respiratory tract. Compared to the avian influenza A (H5N1) virus, H7N9 virus might pose an even more important pandemic threat to human. The research has just been published online today in the international scientific journal, The Lancet Respiratory Medicine.
This research was led by Professor Malik Peiris, Tam Wah-Ching Professor in Medical Science and Chair Professor of Virology, School of Public Health and Professor John Nicholls, Clinical Professor of The Department of Pathology, The University of Hong Kong Li Ka Shing Faculty of Medicine. Professor Malik Peiris gives remarks, ?The research team has made use of a human respiratory tract ex vivo explant culture system to show that the H7N9 viruses are better adapted to infect and replicate in the human respiratory tract than other avian influenza viruses. The ability of avian influenza viruses to infect the human airways (trachea, bronchus) determines how readily these viruses can jump from birds to humans, to assess the adaptability of the virus in human and to potentially adapt to human-to-human transmission. Hence the findings are crucial for the future research.?



Research findings
The researchers used human respiratory tract tissues (bronchus and lung) maintained in culture to compare infection with the avian influenza A (H7N9) virus, the 2009 pandemic influenza A (H1N1) virus (commonly known as swine influenza) and highly pathogenic avian influenza A (H5N1) virus. They find that the H7N9 virus infects and replicates in both human bronchus as well as the H1N1 virus, and far more efficiently than the H5N1 virus.


These studies also identify the type II alveolar epithelial cells within the lung as a key target for H7N9 virus replication. This is the key cell type supporting regeneration and repair of damaged lung tissues. Thus infection and damage to these cells will prevent the repair processes that allow the lung to recover from injury or infection.

Taken together, this study demonstrates that the H7N9 viruses are better adapted to infect and replicate in the human airways and pose an important pandemic threat, perhaps even more so than H5N1 virus.
Research background
Since February 2013, there have been 134 laboratory-confirmed human influenza A (H7N9) virus infections reported. There have been 43 deaths so far. The source of human infection appears to be poultry. There is so far no evidence of sustainable human-to-human transmission within the community.

http://www.med.hku.hk/v1/press-releases/hku%E2%80%99s-finding-on-avian-influenza-a-h7n9-virus-well-adapted-to-infect-human-respiratory-tract-reveals-why-numerous-human-infected-cases-in-a-short-period-of-time/