Genomic analysis of database might point to deadly mutations
By Susan Brown (email@example.com) | January 27, 2006
By sequencing genes from a large and historic sample of avian influenza viruses, scientists say they have found a genetic marker that may determine which strains of bird flu are mild and which are deadly. The study, published online in this week?s Science, nearly doubles the amount of genetic information about the viruses, and introduces what the authors claim is a new approach to comparing genetic variation.
?They have created a resource for discovery,? David Lipman, director of the National Center for Biotechnology Information and an expert in comparative genomics and molecular evolution told The Scientist. ?There simply hasn?t been this much avian flu sequence available,? he said. ?This is a very important resource. It?s a huge jump for the entire community.?
During the study, Clayton Naeve and colleagues at St. Jude Children?s Research Hospital in Memphis, Tennessee looked at 336 viral samples from wild birds and domestic poultry. The group sequenced more than 2,000 influenza genes and deposited the data -- including 168 complete genomes -- in GenBank.
Naeve and his team also compared the sequences with existing genetic data for flu isolated from humans, birds, and other animals. In addition to constructing traditional phylogenetic trees, they used a new method they call proteotyping, which focuses on amino acid sequences that vary most between strains of the virus, to highlight potentially important regions of viral proteins. ?We?re able to identify viruses that share the same molecular signature,? said lead author John Obenauer.
The method pinpointed a protein signature for one gene, NS1, that is shared by the majority of flu viruses isolated from birds, but is not found in most strains isolated from humans-- suggesting this sequence may help explain why avian flu can be so lethal when it first infects humans.
?They show fairly convincingly the potential for signaling interactions between NS1 and several other genes important for cell function,? said Ruben Donis, head of the molecular genetics section at the Center for Disease Control?s influenza surveillance program. ?It really shows the promise of this approach.?
However, virologist Robert Krug of the University of Texas in Austin, who studies the structure and function of NS1 and other viral proteins, said he remains skeptical. ?They haven?t done the experiment,? he said, noting it would be a relatively simple matter to delete the suspect portion of the protein. If mammalian cells or animals infected with a modified virus became only mildly sick, he would be convinced, Krug noted.
Naeve admitted that the findings are preliminary. ?We have no physical evidence that that protein is responsible for virulence,? he said. ?We expect that the influenza community will jump on this and do lots of experiments to further define whether or not it does indeed contribute to virulence.?
The group at St. Jude?s also found large variation in viral surface proteins ? an expected finding, they said, given that influenza virus mutates rapidly to evade detection by the immune system.
Naeve noted that he and his group are continuing their sequencing work, and hopes that others will use their proteotyping approach to pinpoint genetic changes to watch out for when monitoring bird flu. ?I think we?ve just scratched the surface of what can be discovered in this data set.?
Links within this story
JC Obenauer et al. "Large scale sequence analysis of avian influenza isolates," Science Express, published online 26 January 2006.
National Center for Biotechnology Information
S. Pincock, ?UK sends flu mission to Asia,? The Scientist, October 21, 2005.
I.Ganguli, ?Flu genome sequenced,? The Scientist, October 6, 2005.
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