January 25, 2006

Scientists Solve Puzzle of Flu Virus Replication

By Patricia Reaney

LONDON (Reuters) - Scientists have solved the genetic puzzle of how influenza A viruses -- including the H5N1 bird flu -- replicate inside cells, which could help to speed up the development of new drugs to avert a pandemic.

As governments bolster efforts to halt the spread of avian flu which has killed 83 people since 2003, an international team of researchers has discovered that the flu virus infects cells by organizing its genetic material in a set of eight segments.

"We've found that the influenza virus has a specific mechanism that permits it to package its genetic materials," said Professor Yoshihiro Kawaoka, of Wisconsin-Madison School of Veterinary Medicine, who headed the research team.

"All influenza viruses have the same mechanism, including bird flu," he added in an interview on Wednesday.

Influenza A is the family of viruses responsible for seasonal flu as well pandemic strains such as the 1918 Spanish Flu that killed as many as 50 million people worldwide.

Scientists fear H5N1 could cause the next pandemic if it mutates on its own or mixes with a human virus to form a strain that can spread easily from person to person.

So far it has not shown it is highly infectious in humans but knowing how the virus replicates and the mechanism that controls it could provide new targets for antiviral drugs.

"If we can disrupt this interaction ... we may be able to stop the virus replication," said Kawaoka, who is also a professor at the University of Tokyo in Japan.

UNWRAPPING THE PACKAGE

Influenza A viruses enter cells and reproduce their own genetic material, or RNA, into infectious particles that are released and then infect other cells. How it manages to do it has been a mystery, until now.

With the help of an electron microscope, Kawaoka and a team of scientists from Japan, Sweden, and the United States used a technique that generates three-dimensional images to see how the virus packages the segments of RNA into the infectious particles.

They found the material is organized in a circle of seven RNA segments surrounding another segment to make a set of eight. Kawaoka said no one had identified that before.

"We need to have more antivirals for influenza," said Kawaoka, who reported his research in the journal Nature.

"And as these segments get incorporated into the particle as a set, it suggests these elements could be a target of disruption. There must be a genetic element in each of the eight segments that allows them to interact," he added.

The scientists are trying to identify what is important for the interaction among the eight segments and are looking for molecules that will inhibit it, to prevent the virus from replicating.