Avian Flu Diary: Eurosurveillance:The Evolving Threat From New, Reassorted H7N9 Viruses

The H7N9 Reassortment – Credit Eurosurveillance

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If there is one constant with influenza viruses, it is their propensity to continually change and evolve.

As a virus that leaves behind a degree post-infection immunity, were it not to change over time, it would quickly run out of susceptible hosts.

And without a constant supply of hosts, it cannot survive.

Sometimes change comes about gradually, through a process called antigenic drift.

This is the evolutionary process that creates small, incremental changes in the virus over time. Drift is the standard evolutionary process of influenza viruses, and comes about due to replication errors that are common with single-strand RNA viruses (see NIAID Video: Antigenic Drift).

More abrupt changes come from antigenic shift, also called reassortment. For shift to happen, a host (human, swine, bird) must be infected by two influenza different viruses at the same time.

And the H7N9 virus which emerged last spring, sprung forth out of a series of reassortments between H7 avian viruses and avian H9N2.

While successful reassortment is relatively rare, as any virologist will tell you . . . Shift happens.

Shift occurs when one virus swap out chunks of their genetic code with gene segments from another virus. While far less common than drift, shift can produce abrupt, dramatic, and sometimes pandemic inducing changes to the virus (see NIAID Video: How Influenza Pandemics Occur).

And so one of the things we have been watching for with the H7N9 virus are any signs that it continues to reassort with the H9N2 virus. Recent studies (see PNAS: Reassortment Of H1N1 And H9N2 Avian viruses) have confirmed this virus’s ability to swap genes with many other flu strains.

Which brings us to a new Rapid Communications from Chinese scientists, published today in the journal Eurosurveillance, that describes at least three new reassortments of the H7N9 virus.

Eurosurveillance, Volume 19, Issue 6, 13 February 2014

Rapid communications

Possible pandemic threat from new reassortment of influenza A(H7N9) virus in China

Z Meng¹, R Han², Y Hu¹, Z Yuan¹, S Jiang¹, X Zhang¹^,3, J Xu

Avian influenza A(H7N9) virus re-emerged in China in December 2013, after a decrease in the number of new cases during the preceding six months. Reassortment between influenza A(H7N9) and local H9N2 strains has spread from China's south-east coast to other regions. Three new reassortments of A(H7N9) virus were identified by phylogenetic analysis: between A(H7N9) and Zhejiang-derived strains, Guangdong/Hong Kong-derived strains or Hunan-derived A(H9N2) strains. Our findings suggest there is a possible risk that a pandemic could develop.

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Although you’ll want to read the entire report, the discussion section nicely sums up their findings, including the discovery of new reassortants in both Guangdong & Zhejiang Provinces, the areas which have reported (by far) the greatest number of cases during this second wave.

Discussion

Our analysis revealed dynamic reassortments between influenza A(H7N9) and A(H9N2) viruses since the outbreak of A(H7N9) virus infection in March 2013.To some extent, the continuous transmission of H7N9 in Chinese poultry has led to increasing diversity and new reassortment of A(H7N9) with local A(H9N2) strains. Our findings suggest that the re-emerged H7N9 infections may be triggered by new reassortment strains, such as those in the Guangdong/Hong Kong transmission of Cluster 3. In this regard, these infections may have implications for the traditional strategies of drug and vaccine development targeted against HA and NA genes [15].In particular, the new reassortments generated by A(H7N9) and local A(H9N2) strains may produce avian influenza virus strains that are more adaptive and have a higher pathogenicity in humans [16], emphasising the importance of continuously monitoring the A(H7N9) epidemic.

To date, 127 cases of A(H7N9) virus infections have been reported in January 2014, almost the same number as reported in the spring of 2013 (n=133) [5,6]. Notably, Zhejiang and Guangdong provinces and the Shanghai metropolitan area, where new reassortment of A(H7N9) strains is being identified, have been the worst affected regions in China in 2014 [1,17,18]. Although the case-fatality rate in January 2014 (24%, 31/127) is not higher than that seen in the spring of 2013 (29%, 39/133) [5,6], the rapidly increasing number of cases of A(H7N9) virus infection in these three regions may raise concerns as to whether there is an association between circulation of the new A(H7N9) reassortment strains identified and accelerated transmission of A(H7N9) virus in humans. Therefore, it is of the utmost importance to monitor the risk of a potential pandemic initiated by various influenza virus strains.

While most reassortant viruses are evolutionary failures, and are ultimately unable to compete with the existing wild viruses, every once in awhile a new one will appear that is both biologically fit, and capable of sparking an epidemic or even a pandemic.

While the H7N9 virus hasn’t yet gained the ability to transmit efficiently from human to human, as long as it continues to circulate widely in poultry along side H9N2 (or any other compatible flu strains), it will continue to get more free rolls with the genetic dice.

Although it may make thousands of unsuccessful rolls, it only has to get `lucky’ once, to be a game changer.

For more on the evolution of the H7N9 virus, you may wish to revisit: