Saturday, December 03, 2016

Cell Host Microbe: Genesis, Evolution and Prevalence of HPAI H5N6 In China


Almost from the time it was first observed in a Sichaun poultry dealer in the spring of 2014, HPAI H5N6 - a reassortment of H5N1 and H6N6 - had the ring of becoming the heir apparent to the venerable and long-ruling H5N1 virus.

During the summer of 2014, the virus appeared sporadically in China, Vietnam and Laos, killing poultry, but with only the one human infection reported from the spring.

A little over six months after it emerged, with just a hand full of studies on the new virus, we looked at the FAO-EMPRES Report On The Emergence And Threat Of H5N6  which somewhat presciently warned:
The epidemiological and genetic analysis described above show that the virus is still more adapted to avian-type than  human-type respiratory receptors. However, with winter season approaching in eastern Asia, the prevalence of the virus in poultry is expected to rise, increasing both chances for human exposure and opportunities for mutation or reassortment, especially considering the location of circulation of this virus: in endemic regions with H5N1, H9N2 and H7N9 for China. The latter could change the viruses’ transmissibility to humans. H5N6 therefore remains a public health threat, which requires close monitoring in the same way as for H5N1 HPAI and H7N9. 

While H5N6 was slower off the mark than H5N8, it has blossomed in the past 12 months, sparking at least a dozen human infections in the past year (see map above), and recently spreading out of China and into South Korea and Japan.

Last night Lisa Schnirring, writing for CIDRAP News, looked at a study released this week in Cell Host Microbe on the evolution of the H5N6 virus in her article H5N8 expands in France as H5N6 strikes more Korean farms, in which she writes:

The virus has become one of the dominant subtype in southern China, especially in ducks, replacing H5N1, the group wrote. Their genetic analysis showed 34 distinct H5N6 genotypes, including 4 that have infected people. One of the 4 was linked to five human illnesses.

"These findings combined with our results demonstrate that H5N6 viruses pose a considerable threat to public health despite the limited number of human cases," they concluded.

Lisa does her always terrific job of summarizing the report, so I'll not duplicate her efforts here. If you aren't reading CIDRAP's excellent coverage of infectious disease threats, you really should.

The full article is behind a pay wall, but the Abstract is at the link below:


•Live poultry markets in China surveyed for avian influenza viruses during 2014–2016
•H5N6 has replaced H5N1 as a dominant AIV subtype in southern China, especially in ducks
•The HA and NA genes of H5N6 show apparent lineage-specific matching patterns
•At least 34 distinct H5N6 genotypes noted, one responsible for five human infections

Constant surveillance of live poultry markets (LPMs) is currently the best way to predict and identify emerging avian influenza viruses (AIVs) that pose a potential threat to public health. Through surveillance of LPMs from 16 provinces and municipalities in China during 2014–2016, we identified 3,174 AIV-positive samples and isolated and sequenced 1,135 AIVs covering 31 subtypes.

Our analysis shows that H5N6 has replaced H5N1 as one of the dominant AIV subtypes in southern China, especially in ducks. Phylogenetic analysis reveals that H5N6 arose from reassortments of H5 and H6N6 viruses, with the hemagglutinin and neuraminidase combinations being strongly lineage specific. H5N6 viruses constitute at least 34 distinct genotypes derived from various evolutionary pathways.

Notably, genotype G1.2 virus, with internal genes from the chicken H9N2/H7N9 gene pool, was responsible for at least five human H5N6 infections. Our findings highlight H5N6 AIVs as potential threats to public health and agriculture.

With at least 34 distinct genotypes of the virus in circulation (and undoubtedly more to come), H5N6 is embarked on multiple evolutionary pathways with unpredictable results.

Some - perhaps most - will eventually fall by the wayside, overtaken by more biologically `fit' viruses. But it only takes one to succeed. 

This growing diversity of genotypes also means that the behavior (or threat from) H5N6 in one location may not match what we've seen elsewhere or in the past.   Influenza viruses - particularly those as promiscuous as clade H5 viruses - are a constantly moving target.
Last May, in J. Virology: H5N6 Receptor Cell Binding & Transmission In Ferrets, we looked at a report on H5N6 isolates collected from Chinese waterfowl in 2013-2014, that found them not only `fully infective and highly transmissible by direct contact in ferrets', but that they also had a `high affinity' to binding to human α2-6 receptor cells.

Only time will tell if H5N6 becomes the next big pandemic threat. But one trend does seem obvious; the number and diversity of avian flu threats is increasing each and every year.

Since 2013 we've seen scores of new of genotypes of H7N9, H5N8, H5N2, H5N6, and others. And it seems the more of them in circulation, the more `spare parts' and opportunities for  reassortment that are available.

The one thing all of these studies show is that HPAI, like time, marches on. 

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