Tuesday, January 09, 2018

J. Infect.: Pathogenicity & Transmissibility of 3 Avian H5N6 Viruses Isolated From Wild Birds


While it is self-evident to most of my readers, it is worth repeating: because of unceasing evolution - viruses are works in progress.  What we observe today in terms of their genetics, and their behavior, is subject to change over time.
Some viruses are relatively stable, taking a long time to evolve,  while others can mutate at a dizzying speed.
Influenza A viruses, because they can evolve both by antigenic drift (see NIAID video Influenza: Get the (Antigenic) Drift), and by antigenic shift (reassortment) (see NIAID Video: How Influenza Pandemics Occur), are particularly adept at the evolution game.

When you add in a diverse host range (humans, birds, pigs, horses, etc.), 18 (known) HA types and 11 (known) NA types, and anthropogenic factors like live bird markets, and large commercial poultry flocks, and you have the ingredients for rapid, sometimes explosive evolutionary change.
With these evolutionary steps comes considerable diversity, even within individual influenza subtypes.
When we talk about H3N2 seasonal flu, there are at least 7 distinct genetic groups in circulation since 2009 (see The Enigmatic, Problematic H3N2 Influenza Virus), all jostling for dominance on the world stage.  New clades and subclades of H1N1 and H3N2 are continually evolving.

The number of novel flu viruses is even greater, with some subtypes sporting dozens of genotypes, all following their own evolutionary path in the wild.  More than a year ago there were at least 34 known genotypes of H5N6 (see Cell Host Microbe: Genesis, Evolution and Prevalence of HPAI H5N6 In China) - four of which had infected humans.
Some of these genotypes are evolutionary failures - appearing only briefly - only to be replaced by more `biologically fit' and competitive viruses. 
But enough of them co-circulate so that whenever we see a study on the transmissibility and pathogenicity of a particularly influenza subtype (as we did last Friday in mSphere: Human Clade A/H5N6 Influenza Virus Lacks Mammalian Adaptation Markers) we have to remind ourselves we are looking at a snapshot in time of a particular isolate from a much larger, fairly complex array of similar viruses. 
Hence, their findings and conclusions don't always concur.
Today we've another series of snapshots of the Asian H5N6 avian flu virus taken in 2014-2015, published in the Journal of Infection, that finds a progression in replication and pathogenicity of H5N6 viruses isolated from wild birds in Southern China over time. 
Pathogenicity and transmissibility of three avian influenza A (H5N6) viruses isolated from wild birds

Yinfeng Kang, Xuejuan Shen, Runyu Yuan, Bin Xiang, Zhixin Fang, Robert W. Murphy, Ming Liao , Yongyi Shen,  Tao Ren

 DOI: http://dx.doi.org/10.1016/j.jinf.2017.12.012

    •Ducks can carry and shed the three H5N6 HPAIVs, but show no ill effects.
    •These H5N6 HPAIVs can efficiently infect, transmit and cause death in chickens.
    •These viruses are highly pathogenic to mice.
    •These viruses may pose a potential threat to poultry industry and public health.


Since 2013, highly pathogenic H5N6 avian influenza viruses (AIVs) have emerged in poultry and caused sporadic human infections in Asia. The recent discovery of three new avian H5N6 viruses – A/oriental magpie-robin/Guangdong/SW8/2014 (H5N6), A/common moorhen/Guangdong/GZ174/2014 (H5N6) and A/Pallas's sandgrouse/Guangdong/ZH283/2015 (H5N6) – isolated from apparently healthy wild birds in Southern China in 2014–2015 raises great concern for the spread of these highly pathogenic AIVs (HPAIVs) and their potential threat to human and animal health.

In our study, we conducted animal experiments and tested their pathogenicity in ducks, chickens and mice. Ducks can carry and shed the H5N6 HPAIVs, but show no ill effects. On the other hand, these H5N6 HPAIVs can efficiently infect, transmit and cause death in chickens. Due to the overlap of habitats, domestic ducks play an important role in circulating AIVs between poultry and wild birds.
Our results raise the possibility that wild birds disseminate these H5N6 HPAIVs to poultry along their flyways and thus pose a great threat to the poultry industry.

These viruses are also highly pathogenic to mice, suggesting they pose a potential threat to mammals and, thus, public health. One virus isolated in 2015 replicates much more efficiently and is more lethal in these animals than the two other viruses isolated in 2014. It seems that the H5N6 viruses tend to be more lethal as time passes. Therefore, it is necessary to vigilantly monitor H5N6 HPAIVs in wild birds and poultry.

It should be noted that this study deals with the Asian H5N6 virus which emerged in late 2013 and has caused at least 18 human infections in China, and is not the same lineage as the H5N6 viruses reported this fall in South Korea, Japan, and the Netherlands.

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