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Team of researchers advances effort to find drugs to thwart evolving viruses
(Milwaukee Journal Sentinel, The (KRT) Via Acquire Media NewsEdge) MILWAUKEE, Wis. _ A team from the University of Wisconsin-Madison is one step ahead of a quickly evolving influenza virus that's been threatening the planet with pandemic disease for the past five years.
The team, under Yoshihiro Kawaoka, is leading the charge to find new drugs and weapons to fight a virus that has evolved to resist the only drugs known to beat it.
Using a novel approach to screen for genes that aid and abet flu viruses, Kawaoka's team has opened the door for the rapid development of new anti-viral drugs _ drugs needed to combat quickly evolving viruses, such as avian flu, that threaten to cause widespread sickness and economic devastation.
The paper is published Thursday in the journal Nature.
"This is an imaginative and creative team that has consistently impressed me with their approach" to combating and understanding viruses, said William Schaffner, a flu expert at Vanderbilt University, who was not involved in the research.
"This was a really clever proof-of-concept paper," he said. "I think it's a preview of coming attractions, so stay tuned."
For several years, Kawaoka and his colleagues had been searching for ways to identify those genes in human cells that the flu virus requires to replicate.
Viruses work by hijacking genes, proteins and carbohydrates from their victims' cells.
"Viral infection is like classic guerrilla warfare," said Paul Ahlquist, a microbial virologist at UW who was part of the team. "All the steps in viral infection require host factors. The question is what are they and what do they do?"
Kawaoka, Ahlquist and an international team that included scientists from Japan and Indonesia turned to the fruit fly.
"We know an incredibly large amount about the genetics of the fruit fly," Schaffner said.
So, it seemed a natural model for identifying genes involved in influenza infection.
Because fruit flies aren't natural hosts of avian or human flu, the team had to alter the viruses so that they could infect fly cells. Once the cells were infected, the team screened more than 13,000 genes to see which ones responded to the virus.
After several rounds of screening, the researchers focused on just over 100 genes.
Then the team chose the human counterparts of three interesting genes for further testing
To test whether these genes were used by influenza to infect cells, the researchers turned each of the genes off. If the cell resisted infection, the scientists knew the gene was involved.
In all three cases, the team discovered that the genes were essential for viral infection.
Kawaoka says the team is now testing the other hundred or so genes in human cells to see what their role in the infection process is.
The screening process allows the researchers to identify the needs of the virus. In so doing, scientists can tinker in the formulation of new drugs that will stop a virus from commandeering a cell.
For viruses such as avian H5N1 influenza, which has already evolved to resist the anti-viral drugs used to stop it, such knowledge is vital.
But as Kawaoka pointed out, the new approach will "allow others to do the same thing for different viruses."
He said the new system could speed the development of drugs for many different viral diseases, including AIDS.
Kawaoka last year founded FluGen Inc., a Madison company that develops influenza vaccines and treatments. The company last month signed licensing agreements with the Wisconsin Alumni Research Foundation for a technology it says could significantly improve the way flu vaccines are manufactured.
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(Milwaukee Journal Sentinel correspondent Kathleen Gallagher contributed to this report.)
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(c) 2008, Milwaukee Journal Sentinel.
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Copyright ? 2008 Milwaukee Journal Sentinel
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