Lancet: Tropism Of H7N9 In the Human Respiratory Tract

 

ex vivo bronchus culture – Credit University Of Hong Kong

 

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An important new study from researchers at the University of Hong Kong appears today in The Lancet Respiratory Medicine, that finds that China’s emerging H7N9 virus infects and replicates in the cells of the human respiratory tract about as well as the 2009 H1N1 virus.

 

While we’ve seen a welcome reduction in human H7N9 infections over the summer, this is the latest in a series of studies that suggests this virus may have substantial pandemic potential (for more see Science: H7N9 Transmissibility Study In Ferrets).

 

In today’s study, researchers led by Dr. Malik Peiris inoculated in-vitro and ex-vivo cultures representing human bronchus and lung tissues with six different virus strains (H5N1, H1N1, 2 Human-derived H7N9 strains, 1 duck-derived H7N9, and the H7N7 2003 Netherlands outbreak stain)  and compared how well they infected and replicated within the cells. 

While the duck-derived H7N9 failed to replicate, both human H7N9 viruses replicated efficiently, far better than H5N1, and on a par with the 2009 H1N1 pandemic virus. 

 

We’ve three stops this morning for this paper, after which I’ll return with a bit more. 

 

First, a link to the abstract in the Lancet, then a companion piece by Jessica A Belser & Terrence M Tumpey of the CDC’s NCIRD, and finally a press release from the University of Hong Kong on this research.

 

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

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

ABSTRACT (Excerpt)

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

 

 

In a companion article, Belser and Tumpey explore these findings further (full access with free registration) in:

 

Tropism of H7N9 influenza viruses in the human respiratory tract

Jessica A Belser a, Terrence M Tumpey a

 

While referring to the `remarkable ability of this low pathogenic avian influenza virus to cause severe human disease’  the authors caution that this study leaves a good many questions unanswered.

And our last stop is a press release from the University of Hong Kong (excerpts below).

 

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

25 Jul 2013

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. 

<SNIP>

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.

 

 

This latest research, along with a number of other recent studies, continue to show that the H7N9 virus has many of the qualities we would expect to find in an pandemic strain of influenza:

 

• it is a novel strain to which humans appear to have little or no immunity
• it can infect human (a2,6) receptor cells
• it replicates efficiently in human tissue;
• and it is capable of producing severe disease.

 

Yet, despite these worrisome traits in the lab, we’ve not seen sustained human-to-human transmission of the virus in the field. 

 

Exactly why that is, and whether or not this virus can gain the necessary changes to overcome that limitation, remain unanswered.

 

About the only thing we can say with any certainty is that none of the studies we’ve seen  over the summer have done anything to lower the level of concern over this emerging virus.

 

Which is why all eyes will be on China later this year to see if, and with how much vigor, this virus returns in the fall or winter.

H7N9: Malik Peiris Video Interview

 

 

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Malik Peiris is the Chair Professor of Microbiology at The University of Hong Kong, a Virologist at the Queen Mary Hospital and the Scientific Director of the HKU-Pasteur Research Centre at Hong Kong.

 

And if that weren’t enough, Peiris was also one of the genuine heroes of the SARS outbreak in 2003. He and his team were the first to identify the causative agent  (coronavirus) behind that epidemic.

 

 

Today we’ve a 7 minute video interview with Professor Peiris, courtesy of the Wall Street Journal (follows a brief commercial).

 

 

Could H7N9 Become the World’s Next Flu Pandemic?

The World Health Organization warns that birds seem not be the only means of H7N9 transmission. Professor Malik Peiris, a key investigator of the virus, tells us what we need to know about prevention.

Malik Peiris Newspaper Interview

 

 

 

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Malik Peiris is the Chair Professor of Microbiology at The University of Hong Kong, a Virologist at the Queen Mary Hospital and the Scientific Director of the HKU-Pasteur Research Centre at Hong Kong.

 

And if that weren’t enough, he was also one of the genuine heroes of the SARS outbreak in 2003. Peiris and his team were the first to identify the causative agent  (coronavirus) behind that epidemic.

 

You can read a brief profile of Peiris, and Guan Yi -another famed researcher and hero of that crisis - HERE written by Karl Taro Greenfeld.

 

And since I mentioned him, there is probably no better narrative of the SARS outbreak than Karl Taro Greenfeld’s  The China Syndrome: The True Story of the 21st Century's First Great Epidemic.

 

Today we’ve a long, and informative interview with Professor Peiris appearing in The Hindu newspaper.   It is well worth reading in its entirety.

 

Among the subjects discussed, Peiris argues that trying to make severity a criteria for declaring a pandemic is ill advised.  That it is virtually impossible to gauge the virulence of an influenza virus during the opening months of an outbreak.

 

He also warns that we need to do a better job of surveillance in animals for reassortant viruses, and explains that H5N1 probably has some ways to go before it could ever become adapted to humans. 

 

A hat tip to @CP_Branswell on Twitter for sending this link out.

 

 

Severity should not be part of pandemic criterion

July 29, 2010

 

At a time when the World Health Organisation (WHO) is being criticised for over-reacting and declaring a pandemic of the basis of only geographical spread of a novel flu virus, a leading virologist has argued that severity should not be included as a criterion.

 

Long before WHO's declaration, there was no doubt that this was a pandemic, observed J.S. Malik Peiris. He leads a multi-disciplinary research programme at the University of Hong Kong, studying emerging viral diseases, including influenza, which spread from animals to humans.

 

“It was a new virus, which we didn't know about, and [it] swept across the world,” he pointed out at a recent conference on the current pandemic organised by the University of Hong Kong's Journalism and Media Studies Centre.

 

“If it had been just marginally more severe, we would have been shouting a different tune right now,” he remarked when this correspondent met him after the conference.

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