# 5255
The only constant about flu viruses is that they are always changing. Among the world’s viruses, influenza are some of the most adept at reinventing themselves in order to get around mankind’s acquired immunity.
Since influenza strains spread amazingly well, herd immunity can build rapidly. Without the ability to evade this immunity, influenza viruses would soon run out of susceptible hosts.
The two methods that influenza viruses use to evolve are antigenic drift (small mutations, sometimes single amino acid substitutions) and antigenic shift (large, often dramatic changes due to viral reassortment).
Drift happens slowly, and incrementally, and is the reason why the flu vaccine must be updated and changed every year or two.
Shift, or reassortment, happens abruptly when two different influenza viruses co-infect the same host and 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.
Which brings us to a new study, which appears today in the CDC’s EID Journal, that looks at the potential for the 2009 H1N1 virus to reassort with other currently circulating flu viruses and create a more virulent flu strain.
You’ll, no doubt, recognize some of the authors of this paper, notably Ab Osterhaus and Ron Fouchier. I’ve reproduced the link, and the abstract (slightly reformatted for readability) below.
Volume 17, Number 2–February 2011
Research
Possible Increased Pathogenicity of Pandemic (H1N1) 2009 Influenza Virus upon Reassortment
Eefje J.A. Schrauwen, Sander Herfst, Salin Chutinimitkul, Theo M. Bestebroer, Guus F. Rimmelzwaan, Albert D.M.E. Osterhaus, Thijs Kuiken, and Ron A.M. Fouchier
Abstract
Since emergence of the pandemic (H1N1) 2009 virus in April 2009, three influenza A viruses—seasonal (H3N2), seasonal (H1N1), and pandemic (H1N1) 2009—have circulated in humans. Genetic reassortment between these viruses could result in enhanced pathogenicity.We compared 4 reassortant viruses with favorable in vitro replication properties with the wild-type pandemic (H1N1) 2009 virus with respect to replication kinetics in vitro and pathogenicity and transmission in ferrets.
Pandemic (H1N1) 2009 viruses containing basic polymerase 2 alone or in combination with acidic polymerase of seasonal (H1N1) virus were attenuated in ferrets.
In contrast, pandemic (H1N1) 2009 with neuraminidase of seasonal (H3N2) virus resulted in increased virus replication and more severe pulmonary lesions.
The data show that pandemic (H1N1) 2009 virus has the potential to reassort with seasonal influenza viruses, which may result in increased pathogenicity while it maintains the capacity of transmission through aerosols or respiratory droplets.
Since you could wait a very long time indeed for reassortments like these to occur naturally - in order to study them – man made flu viruses must be created in the laboratory using reverse genetics.
To simplify matters, these researchers only looked at four laboratory generated reassortments out hundreds of possible combinations, selecting those that replicated well in vitro.
While some of these hybrid viruses were weaker that the original 2009 H1N1 virus, reassortants incorporating the NA (neuraminidase) gene from the seasonal H3N2 virus proved more pathogenic (at least in ferrets).
All of these tested reassortants retained `biological fitness’ and could be transmitted among ferrets through aerosol or respiratory droplets.
The authors state:
We conclude that the pandemic (H1N1) 2009 virus has the potential to reassort with seasonal influenza virus A (H1N1) and influenza virus A (H3N2) and that such reassortment events could result in viruses with increased pathogenicity in ferrets.
Although increased pathogenicity in ferrets cannot be extrapolated directly to increased pathogenicity in humans, ferrets are susceptible to natural infection and respiratory disease and lung pathology develop in a manner similar to that in humans infected with seasonal, avian, or pandemic influenza viruses.
Follow the above link to read about how the tests were conducted, some of the limitations on these sorts of experiments, and additional details on the results.
If all of this sound vaguely familiar, last November we saw another study (see mBio: A/H1N1 Potential For Mutation) that looked at the potential for the 2009 H1N1 virus to become more pathogenic through the more common process; antigenic `drift’.
Their conclusion read, in part:
We report that the emergence of an A/H1N1 pandemic strain of higher virulence is possible and that, despite their lack of detection thus far in humans, viable seasonal/pandemic virus reassortants can be generated.
While both of these studies point to the potential for the 2009 H1N1 virus to either drift or shift to a more virulent strain, when – or even if – that might ever happen is impossible to say.
But they do serve as reminders of how quickly flu strains can change, and of the pressing need to increase our global surveillance capabilities so that we can spot these emerging strains as early as possible.
