Infectious Disease
H5N1 bird flu mutation may not be as lethal as feared
By Kathy Jones
Aug 1, 2006 - 12:16:00 PM

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1 Aug, (foodcosnumer.org) - A bird flu pandemic may not be develop too easily and even if the H5N1 virus does mutate, it may not be as lethal as feared, government researchers reported. Scientists created a new virus using strains of the H5N1 bird flu virus and that of human influenza.

They found that the new virus thus developed is not as dangerous as feared even if it results in a bird flu pandemic. The researchers combined human flu strain, H3N2, and the H5N1 bird flu strain that emerged in Hong Kong in 1997. They found that the new virus lacks "the key property that predicts pandemic spread."

However the H5N1 bird flu strain used in the experiment is an earlier version and is not the same one that is presently causing havoc in Asia, parts of Europe and Africa. In fact the researchers admit that other gene combinations may trigger a lethal mutation.

"We are far from out of the woods in H5N1 on a global scale," said Julie Gerberding, director of the Centers for Disease Control and Prevention. "These data do not mean that H5N1 cannot convert to be transmissible from one person to another person. They mean that it's probably not a simple process and more than simple genetic exchanges are necessary."

The CDC researchers conducted four experiments using reverse genetics to create a virus with both bird flu and human flu genes. This hybrid strain was then injected into ferrets, which has similar respiratory tract cells as man.

Researchers found the virus containing genes from both bird and human flu strains was weaker than either parent virus and caused milder illness and didn't spread easily. "Simple combinations of genes from both parent viruses have not led to enhanced transmissibility in the ferret," Dr. Julie Gerberding stressed.

The findings of the study are published in this week's issue of the Proceedings of the National Academy of Sciences.

The existing H5N1 bird flu strain has raised fears of a pandemic since it is highly virulent and due to the ease of transmission among flocks of domestic birds. Dr Gerberding said that for a mutation to be lethal, three conditions must be met.
* The mutation must create a virus for which humans have no antibodies
* It must be a virus that can cause infection and disease
* Person-to-person transmission must be easily accomplished.

While the current H5N1 strain fulfils the first two criteria, the third and arguably the most dangerous has not yet happened. For the flu virus to transmit easily between persons, genetic changes need to take place over time that would make the virus progressively more transmissible. Or there could be a sudden change as witnessed with the 1957 and 1968 pandemics, Gerberding said.

"We assessed the more sudden approach," said the CDC's Jacqueline Katz, a co-author of the study. "The research was undertaken to better understand what changes are needed for H5N1 to acquire the properties of efficient transmissibility."

Katz said that the one positive that had emerged from their experiments was that the mutation if it does occur would not be a simple process. "We chose to use some that had what we believed the greatest likelihood of being a good virus that grew well and was viable and therefore had the potential for transmission. But there are many other combinations that we could investigate in the future," Katz said.

The ferret model used in the study is a viable one and researchers can continue their work on possible mutations. "We need to continue these studies, and the first study has shown that we now have a good model for continued assessment of more recent strains for their ability to re-assort with human strains, and that is work that is ongoing at the moment," Katz confirmed.

The bird flu virus affects the lower respiratory tract and that is why to date it has not transmitted easily between persons. For the virus to do this it must mutate into a upper respiratory tract virus. If that does happen then the pandemic that is feared could result.

Till date, H5N1 bird flu virus has affected 234 people and killed 134 of them, according to the World Health Organization Most of the deaths have occurred in Asia, mainly in Indonesia and Vietnam. In May, the WHO confirmed limited person-to-person transmission in an Indonesian family cluster, but that has not resulted in any further cases.

A new study appearing last month in Nature suggested that many mutations had taken place in the H5N1 bird flu virus. However the significance of these mutations remains unclear.

The current study says that any mutation may not be as bad as feared since the virus needs to undergo complex processes. But as Dr Katz said, "We've got strains emerging probably as we speak. Let's not use the word 'reassuring' in terms of what might happen with H5N1."