Wednesday, February 26, 2014

The Lancet: H9N2’s Role In Evolution Of Novel Avian Influenzas


Schematic Diagram of Novel A(H7N9) Generation- Credit Eurosurveillance


# 8329


The three novel avian flu strains that currently worry scientists the most – H5N1, H7N9, and the recently observed H10N8 – all share several important features,  which we’ve discussed previously.


  1. They all first appear to emanate from Mainland China
  2. They all appear to have come about through viral reassortment in poultry
  3. And most telling of all, while their HA and NA genes differ - they all carry the internal genes from the avian H9N2 virus


The avian H9N2 virus – unlike the H5 and H7 avian viruses – is not considered a `reportable’ disease by the OIE since it is viewed as a relatively stable LPAI (Low Pathogenic Avian Influenza), not prone to evolving into a more dangerous HPAI form.  It is, however:


  1. Believed ubiquitous across much of Asia’s poultry population
  2. Has occasionally infected humans (see Hong Kong: Isolation & Treatment Of An H9N2 Patient)
  3. And is viewed as having at least some `pandemic potential’ (see H9N2: The Other Bird Flu Threat)


As the diagram at the top of this blog shows, the H7N9 virus is a combination (reassortment) of several different avian flu viruses – with six of its eight genes contributed by the H9N2 virus ( shown in green).  An evolutionary pathway similar to that followed by the H5N1 virus in the mid-1990s, and the recently emerging H10N8 virus in China.

Although categorized by their two surface proteins (HA & NA) Influenza A viruses have 8 gene segments (PB2, PB1, PA, HA, NP, NA, M1, M2, NS1, NS2).


Shift, or reassortment, happens when two different influenza viruses co-infect the same host swap genetic material.  New hybrid viruses may be the result of multiple reassortments, with gene contributions coming from several parental viruses.


In the past, we’ve looked at the propensity of the H9N2 virus to reassort with other avian flu viruses (see PNAS: Reassortment Of H1N1 And H9N2 Avian viruses &  PNAS: Reassortment Potential Of Avian H9N2) which have shown the H9N2 capable of producing `biologically fit’ and highly pathogenic reassortant viruses.


In 2010 (see Study: The Continuing Evolution Of Avian H9N2) we looked at computer modeling (in silica) that warned the H9N2 virus has been slowly evolving towards becoming a `more humanized’ virus.


All of which serves as prelude to a brief report appearing today in The Lancet, where Chinese researchers warn of the threat posed by the H9N2 virus, and call for prompt and bold action to prevent the `next pandemic virus’ from emerging from China’s poultry industry. 


The report is a short one, well worth reading,  and quite to the point. I’ve  only excerpted its conclusions (bolding mine).  Follow the link below to read it in its entirety.



Poultry carrying H9N2 act as incubators for novel human avian influenza viruses

Di Liu a, Weifeng Shi b, George F Gao a c 


Although the contribution of H9N2 genes to infection in human beings needs to be determined, these genes probably enable H7N9 virus to survive and be transmitted within poultry, because dynamic reassortments of H7N9 with H9N2 genes have been observed,5 suggesting that H7N9 virus evolved in poultry to become a virus that infects human beings. Hence, reassortment between the prevalent poultry H9N2 viruses (providing genetic segments) and the influenza virus from wild birds could make the influenza evolve to adapt to domestic hosts. Poultry, especially in live markets, would have a pivotal role during the emergence of a novel influenza virus of avian origin.


Several subtypes of avian influenza viruses in poultry are capable of infecting human beings, and the next avian influenza virus that could cause mass infections is not known. Therefore, slaughter of poultry carrying H9N2—the incubators for wild-bird-origin influenza viruses—would be an effective strategy to prevent human beings from becoming infected with avian influenza.


We call for either a shutdown of live poultry markets or periodic thorough disinfections of these markets in China and any other regions with live poultry markets.


The shutdown of live poultry markets has been a stated goal by Chinese authorities for many years due to the H5N1 threat, but thus far, only limited (and usually temporary) shutdowns have been orchestrated. Despite pretty good evidence that the shutdown of live markets last spring helped quell China’s H7N9 outbreak (see The Lancet: Poultry Market Closure Effect On H7N9 Transmission), there remains strong public pressure to keep them open.


Even more problematic is their call to cull H9N2 infected chickens.  


As most infected poultry are asymptomatic, it would require extensive (and expensive) surveillance and testing just to identify these birds. And of course, given the likely incidence of the virus in Asian poultry,  the economic losses would be substantial. 


At least in China, the MOA (Ministry of Agriculture’s) policy has seemed to revolve around deflecting concerns over avian flu in their poultry supply, rather than addressing it in an organized and substantive manner (see  China’s MOA Disputes Poultry As Source Of H7N9 Infections). 

As we saw last year in  EID Journal: Predicting Hotspots for Influenza Virus Reassortment, China ranks as one of the globe’s top breeding grounds for new flu strains. Which makes the control of these emerging viruses in all the more important. 


For more on reassortment risks, you may wish to revisit:


Eurosurveillance:The Evolving Threat From New, Reassorted H7N9 Viruses
Lancet: Clinical & Epidemiological Characteristics Of A Fatal H10N8 Case
Viral Reassortants: Rocking The Cradle Of Influenza