MADISON -- By comparing influenza viruses found in birds with those of the avian virus that have also infected human hosts, researchers have identified key genetic changes required for pandemic strains of bird flu.

The new work, reported in the Nov. 16 issue of the journal Nature, illustrates the genetic changes required for the H5N1 avian influenza virus to adapt to easily recognize the receptors that are the gateway to human cells.

"We identified two changes that are important," says Yoshihiro Kawaoka, the senior author of the Nature paper and a virologist at the University of Wisconsin-Madison School of Veterinary Medicine. "Both changes are needed for the H5N1 virus to recognize human receptors."

The new report provides a molecular blueprint for the genetic changes required to transform a virus that only infects birds to a virus capable of easily recognizing human receptors. Receptors are molecules on the surface of cells that permit the virus to dock with the cell and commandeer it to initiate a cascade of infection. By knowing what genetic changes are required for the virus to easily infect human cells, it may be possible to detect the emergence of pandemic strains earlier, providing public health officials and vaccine manufacturers with precious time to prepare for a global outbreak of highly pathogenic influenza. To be successful, a virus must be able to recognize and attach to a host cell. But human and avian influenza viruses recognize different cell receptors. Avian flu viruses have demonstrated an ability to evolve to easily infect humans by exchanging genes with human viruses that subsequently permit them to recognize human receptor molecules and gain easy access to cells, typically in the human respiratory system.

The change is thought to occur when human patients are exposed at the same time to a human flu virus and an avian flu virus. Most viruses, including influenza, readily swap genes with one another.

In the new
'"/>

Contact: Yoshihiro Kawaoka
kawaokay@svm.vetmed.wisc.edu
608-265-4925
University of Wisconsin-Madison
15-Nov-2006