Scientists Show Deadly Bird Flu Strain Is Evolving Toward Human To Human Form

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Main Category: Bird Flu / Avian Flu
Also Included In: Genetics;  Veterinary
Article Date: 08 Oct 2007 - 4:00 PDT

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US scientists have shown that the deadly strain of bird flu H5N1 that has so far killed 201 of the 329 people it has infected worldwide since 2003 is gradually evolving to a pandemic form that will spread easily from human to human.

In a study published in the journal Public Library of Science Pathogens, researchers from the University of Wisconsin-Madison (UW-Madison) reported that one key evolutionary step has already been achieved in new forms of the virus that are circulating in Africa and Europe.

Led by virologist Yoshihiro Kawaoka of the UW-Madison School of Veterinary Medicine, the team has identified a single change in a protein on the surface of the virus that enables it to get a foothold in the cells of the upper respiratory system of mammals. The upper respiratory system is the nose and throat.

This step is important because it gives the virus the ability to infect a wider range of cell types and also to spread via coughs and sneezes. However, it is not enough to make it fully contagious from mammal to mammal; other, as yet unknown, mutations would be necessary for that to happen. But Kawaoka and his team suspect that too is just a matter of time.

Kawaoka, an internationally recognized expert on influenza, said in a prepared statement that the viruses that are in circulation today are more mammalian-like than the ones that were circulating in 1997.

"The viruses that are circulating in Africa and Europe are the ones closest to becoming a human virus," he explained.

Bird flu, also called avian influenza, is primarily a virus that infects chickens, ducks, and other birds. There are a number of strains, but the one that also infects humans who come into contact with infected birds is the highly pathogenic H5N1.

Scientists believe that the more opportunity the virus has to infect and populate humans and other mammals the greater the chance it will evolve into a form that is spread easily from human to human. This process may take years because it results from the accumulation of lots of very small changes. This is said to have happened in the case of the Spanish flu of 1918 that killed 30 million people worldwide.

Kawaoka and colleagues isolated two strains of the virus from a single infected patient. One strain was found in the lungs and the other in the upper respiratory system. They then carried out a study on the two strains in mice and found one difference in a surface protein.

The researchers examined position 627 of the PB2 viral protein and found that viruses that had the amino acid Lys (lysine) at this point replicated efficiently in both the lower and upper respiratory systems, and in a wide range of cells, even at temperatures as low as 33 degrees C (91.4 degrees F, the temperature in the human nose and throat).

Viruses that had the amino acid Glu (glutamine) at this point however, did not do so well in the upper respiratory system.

The researchers said this move to the upper respiratory system "may provide a platform for the adaptation of avian H5N1 viruses to humans and for efficient person-to-person virus transmission."

This change enables the virus to replicate more easily at lower temperatures, said the researchers.

Birds have a higher body temperature than humans, so to move to humans the virus was more likely to survive in the lower respiratory system, where it is warmer. However, now it has had a chance to evolve in human hosts, it has taken the next step, and can survive in the nose and throat, where it enters the body, and where it is cooler.

Speculating on whether this step is enough to take the virus to the human to human stage Kawaoka explained that:

"This change is needed, but not sufficient."

"There are other viral factors needed to cause a viral pandemic," he said.

How long it will be before the virus mutates again and takes these other steps is anybody's guess, but the researchers confirmed their view that it will happen and it is just a matter of time.

"Growth of H5N1 Influenza A Viruses in the Upper Respiratory Tracts of Mice."
Hatta M, Hatta Y, Kim JH, Watanabe S, Shinya K, et al.
PLoS Pathogens Vol. 3, No. 10, e133
doi:10.1371/journal.ppat.0030133

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Written by: Catharine Paddock
Copyright: Medical News Today
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