[2008] Three genes can turn normal flu into a killer, University of Wisconsin-Madison researchers find

http://www.madison.com/wsj/topstories/429890

TUE., DEC 30, 2008 - 11:18 PM

By DAVID WAHLBERG 608-252-6125
dwahlberg@madison.com

Three key genes can turn a regular flu virus into a super killer like the strain that devastated the world 90 years ago and one that could come again, University of Wisconsin-Madison researchers found in a study involving ferrets.

The discovery by a team led by virologist Yoshihiro Kawaoka could help scientists better recognize new flu strains capable of causing a global epidemic, or pandemic, and develop drugs to ward off any kind of flu, the researchers said.

"These findings may help us identify virulence factors in other emerging pandemic viruses and could accelerate the development of new antiviral drugs," the scientists wrote in a report on their findings in Monday's online edition of the journal Proceedings of the National Academy of Sciences.

Graphic on reconstructing the 1918 flu virus:
http://www.madison.com/wsj/media/flu/flu.jpg

Kawaoka said the goal was to find out why the 1918 flu virus, known as the Spanish flu, was so deadly, killing up to 50 million people. Many of those who died were young adults who developed pneumonia from infections that penetrated deep into their lungs, something regular flu viruses normally don't do.

In 2004, Kawaoka identified a gene that enables the 1918 virus to latch on to cells in mice, but that wasn't enough to explain the germ's deadly power.

In the new study, he mixed a regular flu virus with the 1918 virus, gene by gene, testing the combinations in ferrets, which have responses to flu that mimic those in humans. One of the resulting viruses, containing a three-gene sequence that produces a virus-replication protein, infected the lower respiratory tracts of the animals, like the 1918 virus did in humans.

"This is a very definitive study," said Peter Palese, chairman of microbiology at Mount Sinai School of Medicine in New York. "It's important to analyze the virus gene by gene."

Kawaoka and other scientists, including Palese, previously reconstructed the 1918 virus from tissue samples extracted from victims of the flu, whose bodies were preserved in Alaska in the permafrost. They used a technique Kawaoka helped develop, called reverse genetics, that has also proven useful in searching for better flu vaccines.

Joining Kawaoka in the new research was lead author Tokiko Watanabe of UW-Madison; Shinji Watanabe, Jin Hyun Kim and Masato Hatta, also of UW-Madison; and Kyoko Shinya of Kobe University.

A bird flu virus known as H5N1 gained significant attention worldwide in 2005 and 2006 because of the threat of it causing a potential pandemic. Though fewer human cases have been reported recently, the virus continues to circulate.

This year, 30 of 40 people known to be infected with H5N1 died, mostly in Indonesia. In 2006, 79 of 155 people reported to be infected died.