Friday, April 28, 2017

J. Virology: Molecular Evolution and Emergence of Avian H5N6

















#12,414


While H7N9 has been the big overachiever this winter, producing the largest and deadliest avian flu outbreak on record, avian H5N6 - despite jumping to South Korea, Japan, and Taiwan - has not been reported as a human infection since November of 2016.

 This respite in human cases, while welcome, is not guaranteed to last.

As with all influenza subtypes, when we talk about H5N6, we're aren't talking about a single viral threat, but rather an expanding array of related viruses sharing similar HA and NA genes. Viruses which can vary considerably in their behavior and the threat they pose (see Differences In Virulence Between Closely Related H5N1 Strains).
Influenza A viruses are broadly categorized by two proteins they carry on their surface; their HA (hemagglutinin) and NA (neuraminidase), producing subtypes like H5N1, H7N9, or H5N6.
Within each subtype there are genetic groupings called clades, and often within each clade - subclades – and within each of these, many genotypes and variants may exist.  Proving that above all else, influenza viruses are both promiscuous and prolific. 



Last December, in Cell Host Microbe: Genesis, Evolution and Prevalence of HPAI H5N6 In China, we saw a report that found that H5N6 had become the dominant HPAI H5 virus in Chinese ducks (replacing H5N1), with 34 distinct H5N6 genotypes, including 4 that have infected people.

The common denominator across all of these genotypes had been that all these H5N6 strains belonged to H5 clade 2.3.4.4.  The same H5 clade that produced the H5N8 outbreaks in Korea in 2014, the North American epizootic of 2015, and this winter's outbreaks across Europe.  
Today we've a new study out of China which confirms the diversity among H5N6 viruses, including one sample that belongs not to clade 2.3.4.4.  -  but is unexpectedly derived from H5N1 clade 2.3.2.

Clade 2.3.2 emerged in central China in 2009 (see 2011 EID Journal New Avian Influenza Virus (H5N1) in Wild Birds, Qinghai, China), and quickly began to appear in migratory birds and poultry from Japan to India, supplanting the old 2.2 clade in many regions.

 It, in turn, has now been largely supplanted by clade 2.3.2.1. (see 2015's Novel H5N1 Reassortment Detected In Migratory Birds - China).

Today's report reaffirms just how diverse the constellation of H5N6 viruses circulating in China really are, and reinforces the need to monitor these viruses closely.  We've the abstract, along with a news release from the Chinese Academy of Sciences to provide additional context.

Molecular Evolution and Emergence of H5N6 Avian Influenza Virus in Central China
Yingying Du1, Mingyue Chen1,Jiayun Yang1,Yane Jia1, Shufang Han1, Edward C. Holmes2 and Jie Cui1 
ABSTRACT

H5N6 avian influenza virus (AIV) has posed a potential threat to public health since its emergence in China in 2013. To understand the evolution and emergence of H5N6 in the avian population we performed molecular surveillance of live poultry markets (LPMs) in Wugang prefecture, Hunan province, in central China during 2014-2015. Wugang prefecture is located on the Eastern Asian-Australian migratory bird flyway and a human death due to an H5N6 virus was reported in the prefecture on 21th November 2016. 


In total, we sampled and sequenced the complete genomes of 175 H5N6 AIVs. Notably, our analysis revealed that H5N6 contains at least six genotypes arising from segment reassortment, including a rare variant that possesses an HA gene derived from H5N1 clade 2.3.2 and a novel NP gene that has its origins with H7N3 viruses. 

In addition, phylogenetic analysis revealed that genetically similar H5N6 AIVs tended to cluster according to their geographic region of origin. These results help reveal the evolutionary behavior of influenza viruses prior to their emergence in humans. 
  
Researchers Reveal a Complex Pattern of the Evolution and Emergence of H5N6 Avian Influenza Virus in central China
Apr 28, 2017    


Since H5N6 avian influenza virus first emerged in China in 2013, it has caused more than ten human deaths in China, which poses potential risks to human health.

In order to further understand the evolutionary behavior of H5N6 prior to its emergence in humans, the research group led by Prof. CUI Jie from Wuhan Institute of Virology of the Chinese Academy of Sciences developed the studies on the evolution and emergence of H5N6 avian influenza virus in central China. 

To better understand the complex molecular evolution and emergence of H5N6 at the local level, the researchers took surveys in the live poultry markets in Wugang prefecture in Hunan province in central China, and tried to reveal the diversity and genomic origins of H5N6 in birds.

Notably, WHO reported and confirmed a human death caused by H5N6 in these live poultry markets on 21th November 2016 in this prefecture. 

During 2014-2015, cloacal swabs and fecal samples from ducks, geese and environmental samples in the live poultry markets in Wugang prefecture were collected and screened for avian influenza virus by the researchers.

Then the complete genomes of 175 H5N6 avian influenza viruse were sampled and sequenced. Their surveillance of H5N6 revealed that at least six types of reassortant H5N6 have circulated in that region, including a rare variant that possesses an HA gene derived from H5N1 clade 2.3.2 and a novel NP gene that has its origins with H7N3 viruses.

As all currently reported H5N6 avian influenza viruses are members of H5N1 clade 2.3.4.4, their observation that one H5N6 virus seemingly carried an HA gene directly derived from H5N1 clade 2.3.2 is of importance.

They suggest that a careful monitoring of H5N6 viruses in the live poultry markets and wild birds is evidently necessary to help prevent the virus from establishing itself in the human population.

In sum, the researchers have revealed a complex pattern of evolution and emergence of H5N6 in a single locality in central China over a two-year period.

The results have been published in Journal of Virology entitled "Molecular Evolution and Emergence of H5N6 Avian Influenza Virus in Central China". 

This work was supported by funding from the National Key Research and Development Program and the CAS Pioneer Hundred Talents Program. 

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