Wednesday, July 09, 2008

Study: Human Adaptation Of The H5N1 Virus


# 2128



The receptor binding domain (RBD) of the H5N1 virus is that area of its genetic sequence that allows it to attach to, and infect, host cells.    Much like a key into a padlock, the RBD must `fit' the host cell in order for it to bind.


Different viruses have an affinity for different types of cells.  That is why most viruses are selective as to what organ systems they attack, or even what species are susceptible.  This explains why a virus might affect a dog, or a cat, or a bird, yet not affect humans. 


This species selectivity is known as a `host range'.  Viruses generally have a fairly narrow host range.


The H5N1 virus is adapted to attach itself to the type of receptor cells most commonly found in the intestinal and respiratory tract of birds.  


These avian receptor cells are called α-2,3 cells.  


Humans have relatively few of these α-2,3 receptor cells. Instead our respiratory tract's receptor cells are mostly of the α-2,6  variety.   


This is why the H5N1 virus doesn't readily infect humans. 


For a more detailed look at RBD's, you might want to read my essay  Looking for The Sweet Spot.


The fear has been that over time, the H5N1 virus would adapt to the human α-2,6 receptor cells, increasing significantly the chances of a pandemic. 



According to a study to be published in the August issue of the Journal of General Virology, scientists have documented how the H5N1 virus mutates once it infects a human body. 


Here is the press release for the upcoming article, then a little discussion.




Pandemic mutations in bird flu revealed


Contact: Lucy Goodchild
Society for General Microbiology


Scientists have discovered how bird flu adapts in patients, offering a new way to monitor the disease and prevent a pandemic, according to research published in the August issue of the Journal of General Virology.


Highly pathogenic H5N1 avian influenza virus has spread through at least 45 countries in 3 continents. Despite its ability to spread, it cannot be transmitted efficiently from human to human. This indicates it is not fully adapted to its new host species, the human. However, this new research reveals mutations in the virus that may result in a pandemic.


"The mutations needed for the emergence of a potential pandemic virus are likely to originate and be selected within infected human tissues," said Professor Dr Prasert Auewarakul from Mahidol University, Thailand. "We analyzed specific molecules called haemagglutinin on viruses derived from fatal human cases. Our results suggest new candidate mutations that may allow bird flu to adapt to humans."


Viruses with a high mutation rate such as influenza virus usually exist as a swarm of variants, each slightly different from the others. These are called H5N1 bird flu quasispecies. Professor Dr Auewarakul and his colleagues found that some mutations in the quasispecies were more frequent than others, which indicates they may be adaptive changes that make the virus more efficient at infecting humans. Most of these mutations were found in the area required for the virus to bind to the host cell.


"This study shows that the H5N1 virus is adapting each time it infects a human," said Professor Dr Auewarakul. "Such adaptations may lead to the emergence of a virus that can cause a pandemic. Our research highlights the need to control infection and transmission to humans to prevent further adaptations."


The research has provided genetic markers to help scientists monitor bird flu viruses with pandemic potential. This means they will be able to detect potentially dangerous strains and prevent a pandemic. The research also gives new insights into the mechanism of the genesis of a pandemic strain.


"Our approach could be used to screen for mutations with significant functional impact," said Professor Dr Auewarakul. "It is a new method of searching for changes in H5N1 viruses that are required for the emergence of a pandemic virus. We hope it will help us to prevent a pandemic in the future."




When a virus infects a host, such as a bird, or a mammal, it begins to replicate at an enormous rate.  It makes millions, and then billions, of copies of itself.    Influenza viruses have notoriously bad quality control when it comes to making copies, and often mistakes, or mutations are produced.



Many of these mutations will be evolutionary dead-ends, but with multiple mutations going on inside a body at the same time, the better adapted viruses will flourish and thrive.  



It is this host-driven evolution that worries scientists. 



Each human infection is viewed as another opportunity for the H5N1 virus to adapt to human receptor cells.  



This study, using virus samples from various organs removed during autopsies, showed the virus doing exactly that.   Adapting each time it infects a human host.



The good news is, the virus hasn't found the right combination to unlock our human receptor cells and unleash a pandemic. 



The bad news is, as long as it is out there infecting humans, is has another opportunity to try.