Saturday, June 20, 2015

J. Virol: Emergence Of AN HPAI H5N9 Virus In China

Avian Reassortment

# 10,239


Up until a couple of  years ago we had essentially only one highly pathogenic avian flu virus of real concern; H5N1.  It emerged in 1996 in Hong Kong, was believed eradicated in 1997, but returned in 2003.  Since then it has become been the scourge of poultry producers in Asia and the Middle East, infected and killed hundreds of people, and has been a perennial pandemic concern for the rest of us.

Recently, however, we’ve seen the emergence of a bevy of new avian flu subtypes; H5N1, H5N2, H5N3, H5N5, H5N6, H5N8 . . .  along with H6N1, H7N9, and H10N8 – all as a product of reassortment.


Reassortment (or Shift )occurs when two viruses infect the same host, and one virus swap out chunks of their genetic code with gene segments from the other (see graphic above).   While far less common than antigenic drift, shift can produce abrupt, dramatic, and sometimes pandemic inducing changes to the virus (see NIAID Video: How Influenza Pandemics Occur).


Influenza A viruses are subtyped by their surface HA and NA proteins. There are currently 18 known HA subtypes and 11 known NA subtypes, which makes many combinations possible.


A  bit confusingly, you can have two (or more) viruses called by the same name, but describing very different viruses.  Hence the venerable Asian H5N1 subtype and the recently emerged North American H5N1 – while related – are different viral entities.


While the reasons behind this sudden explosion in avian flu subtypes isn’t entirely clear, the emergence of a highly promiscuous LPAI H9N2 virus in 2010 (G57) – one that effectively evaded the poultry vaccines in use – seems to have been a major factor (see PNAS: Evolution Of H9N2 And It’s Effect On The Genesis Of H7N9).


There are two broad categories of avian influenza; LPAI (Low Pathogenic Avian Influenza) and HPAI (Highly Pathogenic Avian Influenza).

  • LPAI viruses are quite common in wild birds, cause little illness, and only rarely death.  They are not considered to be a serious health to public health. The concern is (particularly with H5 & H7 strains) that LPAI viruses have the potential to mutate into HPAI strains.
  • HPAI viruses are more dangerous, can produce high morbidity and mortality in wild birds and poultry, and can sometimes infect humans with serious result. The type of bird flu scientists have been watching closely for the past decade has been HPAI H5N1 (and to a lesser extent HPAI H7s & H9s).


Before the middle of the last decade, there was no uniform requirement to report or track LPAI infections.  That changed in 2006 when the OIE made reporting of LPAI H5 & H7 viruses mandatory.  H9N2, however, is not a reportable infection.


Whether it has been H7N9, H5N8, or H10N8, the ubiquitous LPAI H9N2 virus seems to have been a factor in its creation.

This week we are informed of the detection of a new, HPAI avian flu virus in China; H5N9.    (Note: A different H5N9 virus was reported in an outbreak among Ontario Turkeys in 1966)


Like many of the other recent arrivals, it carries gene contributions from H5N1 and H9N2 . . . plus the NA from H7N9.   Whether this virus poses a threat to humans isn’t yet clear, but it does show that the evolution – and expansion – of HPAI H5 viruses continues in China.


After watching the damage wrought by H5N8 – and the reassortants (H5N2, H5N3) it has spawned - another HPAI H5 entry in the bird flu sweepstakes is more than of just passing interest. 



Newly-emergent highly pathogenic H5N9 subtype avian influenza A virus

Yang Yua, Xingbo Wanga, Tao Jinb, Hailong Wanga, Weiying Sia, Hui Yanga, Jiusheng Wua, Yan Yana, Guang Liub, Xiaoyu Sangc, Yuwei Gaoc, Xianzhu Xiac, Xinfen Yud, Jingcao Pand, George F. Gaoa,e and Jiyong Zhoua 


The Novel H7N9 avian influenza virus (AIV), was demonstrated to cause severe human respiratory infections in China. Here, we examined poultry specimens from live bird markets linked to human H7N9 infection in Hangzhou, China. Metagenomic sequencing revealed mixed subtypes (H5, H7, H9, N1, N2 and N9). Subsequently AIV subtypes H5N9, H7N9 and H9N2 were isolated. Evolutionary analysis showed that the hemagglutination and neuraminidase genes of the novel H5N9 virus originated from A/Muscovy duck/Vietnam/LBM227/2012 (H5N1) belonging to Clade and human-infective A/Hangzhou/1/2013 (H7N9), six internal genes were similar to those of the H5N1, H7N9 and H9N2 viruses.

The virus harbored the PQRERRRKR/GL motif characteristic of highly pathogenic AIVs at the HA cleavage site. Receptor-binding experiments demonstrated that the virus binds α-2,3 sialic acid, but not α-2,6 sialic acid. Identically, pathogenicity experiment also showed that the virus caused low mortality rates in mice. This newly isolated H5N9 virus is a highly pathogenic reassortant virus originating from H5N1, H7N9 and H9N2 subtypes. Live bird markets represent a potential transmission risk to public health and the poultry industry.

IMPORTANCE This investigation confirm that the novel H5N9 subtype avian influenza A virus is a reassortant strain originating from H5N1, H7N9 and H9N2 subtypes, which is totally different from those H5N9 viruses reported before. The novel H5N9 virus got a highly pathogenic H5 gene and an N9 gene from human-infecting H7N9, but caused low mortality rates in mice. Whether this novel H5N9 virus will cause human infections from its avian host and become a pandemic subtype, is not known yet. So it is interesting to assess the risk of the emergence of novel reassortant virus with potential transmissibility to public health.