Monday, February 28, 2011

PNAS: Reassortment Of H1N1 And H9N2 Avian viruses



# 5345



We’ve a study published today in PNAS that is shedding new light on the possibility of seeing a biologically `fit’ and virulent novel virus emerge from a reassortment between the H9N2 avian flu and the (former) pandemic H1N1 swine flu.


Researchers in China – using reverse genetics – created 127 hybrid viruses in the laboratory and tested them on mice for compatibility, replication ability, and virulence.


They found that half of the hybrid viruses were biologically `fit’ as far as replication goes, and 8 hybrids were significantly more pathogenic than either of their parental viruses.


A link to the study, followed by excerpt from the abstract, and then I’ll return with more.


High genetic compatibility and increased pathogenicity of reassortants derived from avian H9N2 and pandemic H1N1/2009 influenza viruses

Yipeng Sun,Kun Qin, Jingjing Wang, Juan Pu, Qingdong Tang, Yanxin Hu, Yuhai Bi,Xueli Zhao, Hanchun Yang, Yuelong Shu, and Jinhua Liu


H9N2 influenza viruses have been circulating worldwide in multiple avian species and repeatedly infecting mammals, including pigs and humans, posing a significant threat to public health. The coexistence of H9N2 and pandemic influenza H1N1/2009 viruses in pigs and humans provides an opportunity for these viruses to reassort.


Our results indicate that some avian H9-pandemic reassortants could emerge with a potentially higher threat for humans and also highlight the importance of monitoring the H9-pandemic reassortant viruses that may arise, especially those that possess the PA gene of H1N1/2009 origin.



When it comes to pathogenicity of flu viruses, mice are reasonably good test subjects  . . . but are not necessarily the best physiological surrogates for humans.


The authors of this study are quoted in the media as saying their next step is to repeat these experiments with ferrets and guinea pigs, lab animals that have more human-like respiratory systems.


We’ve discussed reassortment many times before, so those familiar with the concept may wish to skip ahead.


Shift, or reassortment, happens when two different influenza viruses co-infect the same host swap genetic material.


Influenza A viruses have 8 gene segments (PB2, PB1, PA, HA, NP, NA, M1, M2, NS1, NS2).


Which means that any two compatible influenza viruses could conceivably – and under the right conditions – generate more than 250 different combinations by swapping one or more of their 8 (potentially) interchangeable gene segments.


The key words being “under the right conditions”.


If it were easy, or a common occurrence, we’d be up to our hip boots in new, reassorted viruses all the time.


But it happens often enough that we recognize it as a real threat.   Shift is how new pandemic strains are born, and it was precisely the mechanism that created the 2009 `swine’ flu strain.



While the novel H1N1 `swine flu’ virus needs no introduction, the H9N2 avian virus is less well known. It is endemic in poultry across Asia, and while rare, we have seen a handful human infections. 


How often humans are really infected is unknown, since surveillance and testing among poultry farmers in China is practically non-existent.



A few notable H9N2 stories from the past include:


  • In December 2008 I ran a blog featuring an interview in which world famous Hong Kong virologist Malik Peiris cautioned that the H9N2 virus may be circulating far more commonly than we believe. Revisiting A Malik Peiris Interview On H9N2

  • A little over a year ago, in H9N2: The Other Bird Flu Threat, I wrote about the World Health Organization  recommending the creation of a candidate vaccine virus for H9N2. According to the latest vaccine update from the WHO, work continues on that candidate vaccine virus.


Today’s PNAS study, like many others before it  . . .


EID Journal: H1N1 Reassortment Possibilities

mBio: A/H1N1 Potential For Mutation

PNAS: H3N2 And H5N1 Reassortment)


. . .  point out the potential for nature’s laboratory to come up with new, and potentially devastating, flu strains through genetic reassortment. Granted, less virulent hybrid flu strains are also a possibility.


While we may not be able to stop the next pandemic from happening - knowing which dangerous hybrids to look for, and conducting aggressive global surveillance - may help us detect the next outbreak at the earliest possible moment.

And a few extra week’s warning could make all the difference between having a vaccine in time to mitigate the pandemic’s peak, or having it arrive after the worst had passed.