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Pandemic Avian Influenza Evolution

Recombinomics Commentary
February 21, 2005

>> Nancy Cox is the head of the flu division of the United States Centre for Disease Control.

She says research now shows that bird flu is capable of mutating into a form that can spread from humans to humans.

"We found that for the 2003 virus, the virus had actually changed its receptive binding or its ability to bind to the receptors that are in human cells," she said.

"This shows that the virus can actually change in such a way, or has actually changed in the past in such a way, that might make it more easily transmitted from person to person." <<

The above comments on a human receptor binding capability in H5N1 are similar to earlier reports on H9N2 isolates being able to recognize human receptors.  There have been several reports on dual infections involving H9N2 and H5N1 viruses.  The reports of H5N1 human infections in 1997 described isolates that were H5N1, yet the genes for the internal proteins involved in the replication of the virus were of H9N2 or H6N1 origin.  More recently 2003 H9N2 isolates from Hong Kong had H5N1 internal genes.

Since H9N2 is the most common sub-type in Asia, finding reassortants with H9N2 and H5N1 genes is not surprising.  Moreover the genes themselves have changed via recombination.  In some cases the genes are half H5N1 and half H9N2.

Avian influenza changes its genes via recombination, so picking up a human receptor binding domain, or part of such a domain, is also not surprising. H5N1 is clearly evolving toward a pandemic virus with a broader host range, as demonstrated by its ability to infect mammals such as wild and domestic cats, as well as lab mice and ferrets.  Moreover, it can cause hind leg paralysis in ferrets and mice because its tissue tropism is also expanding.

All of this evolution is done in the absence of isolation of H5N1 avian and human reassortants.  The lack of human genes in H5N1 isolates is announced regularly by WHO, as they issue warnings about the expanded host range of H5N1.

The only recently reported avian / human reassortants are those isolated from swine in Korea.  These isolates have been actively ignored by the WHO.  Reporters are simply told that the WHO is aware of the situation in Korea, but there are no announcements or warnings. 

In Korea there are both H9N2 and H1N1 reassortants.  The H1N1 human genes come from the virulent human lab virus WSN/33 which has escaped from a lab and infected swine on farms.  The human virus has both recombined and reassorted with H9N2 avian isolates found in Korea.  Of the 8 genes, these isolates have 7, 5, 4, or 3 human genes.  Moreover, the PB2 gene in some isolates is half human and half avian, while the NA gene is a recombinant between two or more Korean avian genes.

Thus avian influenza has been achieving a pandemic potential on several fronts involving H5N1, H9N2 and human H1N1 genes.  However, the monitoring or even announcing the existence of such viruses remains scandalous.

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