Friday, July 27, 2018

Frontiers Public Health: Live Poultry Trading Drives China's H7N9 Viral Evolution

Credit Frontiers Public Health


As we've discussed many times in the past (see here, here, and here for just a few), the `secret sauce' common across most of China's growing array of avian flu threats has been the donation of internal genes (via reassortment) from an endemic low path poultry virus - H9N2 - which is widely dispersed across Asia and making inroads in the Middle East and Africa.

Of the four avian flu viruses we currently watch with the most concern – H5N1, H7N9, H10N8 and H5N6 – all share several important features (see Study: Sequence & Phylogenetic Analysis Of Emerging H9N2 influenza Viruses In China):
    • They all first appeared in  Mainland China
    • They all  have come about through viral reassortment in poultry
    • And most telling of all, while their HA and NA genes may differ - they all carry some or all of the internal genes from the avian H9N2 virus
While H9N2's involvement can be traced back two decades to the emergence of H5N1, since 2013 we've seen a sudden surge in the number of new avian reassortants appearing in China - nearly all carrying the incriminating fingerprints of H9N2.
This increase in reassortant avian viruses appears to coincide with recent evolutionary changes in H9N2, which include increased mammalian adaptation.
In 2014, in PLoS Path: Genetics, Receptor Binding, and Transmissibility Of Avian H9N2 researchers found evidence of Chinese H9N2 viruses binding preferentially to alpha 2,6 receptor cells -  the type commonly found in the human upper respiratory tract - rather than to alpha 2,3 receptor cells which are found in the gastrointestinal tract of birds.
H9N2's reach extends beyond just avian flu subtypes, as we've also seen evidence of it reassorting with other influenza viruses, including A Canine H3N2 Virus With PA Gene From Avian H9N2 - Korea and PNAS: Reassortment Of H1N1 And H9N2 Avian viruses.
Aiding and abetting H9N2 in the creation of new viable avian reassortant viruses has been the common practice of housing together many different species of birds and poultry at live bird markets (LBMs), where viruses that might never meet up normally in the wild are provided an ideal environment to reassort. 

Add in transport and trade of poultry between markets (LPTs), and what might have remained local, isolated, outbreaks of a novel avian virus are provided additional opportunities to become regional - or even international - threats. 
We've a new study and analysis published yesterday in Frontiers of Public Health of the impact of both H9N2's genetic contributions, and the influence of LBMs and the poultry trade, on the evolution and geographic spread of H7N9 in China.
It's a long, and at times, technical read.  But well worth following the link to read in its entirety.  I've only posted a few excerpts below.

Live Poultry Trading Drives China's H7N9 Viral Evolution and Geographical Network Propagation
Ruiyun Li1†, Tao Zhang2, Yuqi Bai2, Haochuan Li3, Yong Wang4, Yuhai Bi5, Jianyu Chang6* and Bing Xu1,2*

The on-going reassortment, human-adapted mutations, and spillover events of novel A(H7N9) avian influenza viruses pose a significant challenge to public health in China and globally. However, our understanding of the factors that disseminate the viruses and drive their geographic distributions is limited.
We applied phylogenic analysis to examine the inter-subtype interactions between H7N9 viruses and the closest H9N2 lineages in China during 2010–2014. We reconstructed and compared the inter-provincial live poultry trading and viral propagation network via phylogeographic approach and network similarity technique. 

The substitution rates of the isolated viruses in live poultry markets and the characteristics of localized viral evolution were also evaluated. We discovered that viral propagation was geographically-structured and followed the live poultry trading network in China, with distinct north-to-east paths of spread and circular transmission between eastern and southern regions.
The epicenter of H7N9 has moved from the Shanghai–Zhejiang region to Guangdong Province was also identified. Besides, higher substitution rate was observed among isolates sampled from live poultry markets, especially for those H7N9 viruses. 
Live poultry trading in China may have driven the network-structured expansion of the novel H7N9 viruses. From this perspective, long-distance geographic expansion of H7N9 were dominated by live poultry movements, while at local scales, diffusion was facilitated by live poultry markets with highly-evolved viruses.
Recent analyses demonstrated that the novel H7N9 virus was a reassortant, with surface and internal gene segments originating from wild birds and the H9N2 lineage in poultry, respectively.
This indicates that wild birds were the most likely source of infection, introducing the virus into domestic ducks and chickens through sequential reassortment events, with a consequent spillover to humans by means of live poultry exposure (29).
The resulting multiple H7N9 lineages and genotypes suggest that the evolution of H9N2 has facilitated the genesis of the internal segments of this novel reassortant (4, 10, 11).
It has therefore exhibited greater genetic diversity compared with the surface genes (4, 12). As our preliminary researches have pointed out, this interaction at the wild birds–poultry–humans interface was common in the spread of infectious diseases on various scales (1317).

In the perspective of live poultry trading network in the spatially-structured spread of AIVs presented here, additional interventions should be jointly implemented to restrict viral expansion along LPTs paths and targeted at live poultry workers.
Despite the effectiveness in reducing the daily number and growth rate of new human cases (21, 22) and the amount and detection rate of viable viruses (37) the mandatory closure of LBMs alone was unlikely to eliminate the zoonotic threat (38) accounting for the LPTs as the pathway with the highest likelihood of viral spread2. It is also reported that humans who engaged in the transportation work of live chickens and ducks was particularly susceptible to infections from AIVs (39).
These facts ascertained the role of live poultry trading in the spillover to humans at avian–human interface and the occurrence of H7N9 human cases. Therefore, a multi-sector, cost-effective approach and even international collaboration will be essential for the substantial reduction in the risk of disease spread and the build of a safer trade in animals3.

(Continue . . . )

While H7N9 activity has been greatly suppressed over the past year due to a combination of the introduction and nationwide deployment of a new H5+H7 poultry vaccine - and greater restrictions on live bird markets - the avian flu threat has not gone away. 
H5 and H7 viruses continue to circulate (along with H9N2) in wild bird and poultry, and earlier this year we saw the emergence of a novel H7N4 virus in Jiangsu Province (see UK PHE Guidance & Risk Assessment On Human H7N4 In China).
And despite government interventions, live bird markets continue to operate across much of China, often outside the law.  Add in the transport of live poultry  - identified as a significant threat by this study - and this respite in China's avian flu activity may prove temporary.

But the greater truth is, avian influenza viruses (AIVs) can reassort into human threats anywhere in the world.  The next big avian threat could easily come from Egypt, Indonesia, West Africa, India, or even the United States or Europe.

Because Nature's laboratory is open 24/7, and never takes a break.

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