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UW scientists unravel critical genetic puzzle for flu virus replication

one cell and go on to infect other cells.

What Kawaoka found was that the viruses were assembling their infectious genetic elements in a systematic fashion. Virologists have long debated whether the RNA segments in flu viruses assembled at random into the virions or were somehow incorporated into the infectious particle in an organized way.

The RNA segments, according to Kawaoka, form in a distinct pattern abutting the membrane of the virus. They are always arranged in a circle of seven surrounding another segment for a total of eight RNA fragments.

"It was not really known whether the fragments were coming as a set," explains Kawaoka, whose team conducted the work using a long-studied influenza A virus, the family responsible for regular influenza outbreaks, including such medical calamities as the 1918 influenza pandemic.

The fact that the virus requires a systematic -- as opposed to a random -- method of assembly opens the door to the development of new antiviral drugs and the harnessing of benign influenza viruses as gene vectors to optimize vaccine production, Kawaoka says.

"We need to have more antivirals for influenza," according to Kawaoka, "and as these segments get incorporated into the particle as a set, it suggests these elements could be a target for disruption. There must be a genetic element in each of the eight segments that allows them to interact."

What's more, scientists have been exploring the possibility of using strains of influenza to ferry genes from one virus to another to speed and optimize vaccine production. More efficient methods of vaccine production will be critical should a global outbreak such as the "Spanish " flu pandemic of 1918 recur. That pandemic killed an estimated 30-50 million people.

Knowing how influenza A viruses package their genetic contents, and knowing that they do so systematically, suggests it may be possible, by manipulating key genetic elements, to quickly
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Source:University of Wisconsin-Madison


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