Wednesday, January 14, 2015

Study: H5N5 Receptor Binding


Flu Virus binding to Receptor Cells – Credit CDC


# 9576


Lost in shadow of higher profile H5N1, H5N2, H5N8, and H5N6 viruses is the H5N5 avian virus, which first came to light in a 2011 report (see EID Journal: Novel H5N5 Avian Influenza Detected In China), which described the isolation of two novel reassortant HPAI H5N5 viruses from apparently healthy domestic ducks in Eastern China.


The author’s wrote:

In our study, the 2 reassortant influenza viruses (008 [H5N5] and 031 [H5N5]) and their 3 possible parent viruses (108 [H5N1], 909 [H5N1], and 013 [H6N5]) were all isolated from apparently healthy domestic ducks.

We speculate that domestic ducks may serve as reassortant vessels for creating new subtypes of influenza viruses. In view of the practice of raising ducks in a free-range system, these novel strains could be transmitted to other domestic poultry and even humans.


Several of the same authors wrote about additional isolates of the H5N5 virus in the journal Veterinary Microbiology  (see Characterization of three H5N5 and one H5N8 highly pathogenic avian influenza viruses in China), that were isolated in China in 2009-10, suggesting that the first detection wasn’t a fluke.   


Now the authors of both reports are back with additional information on the receptor binding traits of the H5N5 viruses they’ve isolated, which they published late last month in the journal Veterinary Microbiology.


Novel reassortant H5N5 viruses bind to a human-type receptor as a factor in pandemic risk

Qunhui Lia, Xuan Wanga, Zhao Gaoa, Zhongtao Suna, Zhu Cuia, Zhiqiang Duana, Juan Lia, Min Gua, Xiaoquan Wanga, b, Jiao Hua, b, Xiaowen Liua, b, Xiufan Liua, b,



• H5 viruses continue to spread geographically and evolve rapidly.

• Various NA subtypes of H5 HPAIVs have been detected in different domestic poultry.

• Some natural reassortant H5N5 HPAIVs were isolated from poultry in China.

• These H5N5 viruses bound to both α-2,3 and α-2,6 receptors.

• 031 virus replicated and transmitted efficiently in guinea pigs.


Highly pathogenic avian influenza A(HPAI) H5N1 viruses pose a serious pandemic threat due to their virulence and high mortality in humans, and their increasingly expanding host range and significant ongoing evolution could enhance their human-to-human transmissibility. Recently, various reassortant viruses were detected in different domestic poultry, with the HA gene derived from the A/goose/Guangdong/1/96-like (Gs/GD-like) lineage and the NA gene from influenza viruses of other subtypes. It is reported that some natural reassortant H5N5 highly pathogenic avian influenza viruses were isolated from poultry in China. And their HA genes were belonged to a new clade We evaluated the receptor binding property and transmissibility in guinea pigs of these reassortant H5N5 HPAIVs.

The results showed that these viruses bound to both avian-type (α-2,3) and human-type (α-2,6) receptors. In addition, we found that one of these viruses, 031, not only replicated but also transmitted efficiently in guinea pigs. Therefore, such reassortant influenza viruses may pose a pandemic threat.

In a bit of serendipitous timing, as I was pondering the unusual clade designation of mentioned in the above study, ProMed Mail carried an announcement of a new WHO/OIE/FAO statement creating this new clade (see WHO/FAO/OIE Announce A New H5 Clade (, which I quickly posted.


While not `new’ in the sense of just recently appearing, this clade is now just formally being recognized as a separate branch off the H5 family tree.


Despite binding to both a2,3 and a2,6 receptor cells and (at least one strain) replicating well in guinea pigs, the fact that we aren’t already hip-deep in H5N5 infections tells us regardless of its potential, it isn’t yet ready for prime time. 


Influenza evolution may be inevitable, but random selection takes its own sweet time.


And going from an avian virus to a mammalian virus is a pretty good leap. There may even be an as yet unidentified `species barrier’ that would  effectively keep an H5 or H7 avian virus from fully adapting to mammal hosts (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?). 


Few influenza researchers, however, are willing to bet our collective futures on our being that lucky.


Avian adapted flu viruses bind preferentially to the alpha 2,3 receptor cells found in the gastrointestinal tract of birds, while human-adapted influenza viruses bind to the alpha 2,6 receptor cells commonly found in the upper airway. 


Humans have some a2,3 cells deep in the lungs, which may help explain why avian influenza can sometimes jump to humans, and when it does, often causes severe pneumonia.


But birds run `hotter’ than mammals, and avian viruses replicate best in a bird’s gut, which is much warmer than the upper airway of humans.  Which means mammalian adapted viruses must also adapt to replicate at a lower temperature to be successful in humans.


These are just two examples of obstacles that must be overcome before an avian virus can successfully adapt to human (or mammalian) physiology.  There are undoubtedly more. 


Some we know about, some we probably don’t


Today’s report is a reminder that while the barriers to becoming a humanized flu are substantial, these avian viruses continue to re-invent themselves at a frantic pace, and their growing diversity only increases the odds that one will eventually hit the right genetic combination which could someday threaten mankind.


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