Team Discovers Key Step In Flu Virus Replication

Yan Zhou and her team have discovered how a crucial pathway that supports the influenza A virus's ability to reproduce itself is activated, a finding that could pave the way for new drugs and vaccines.

The paper will appear in the January 2007 issue of the Journal of General Virology and recently has been given advance on-line publication.

"The work we are doing will be applicable to all influenza viruses, including influenza A virus subtype H5N1," said VIDO Director Lorne Babiuk.

Zhou says that although years of research remain to be done, this work provides novel insights for developing live vaccines and antiviral drugs for influenza epidemics and pandemics. A provisional patent has been filed on the findings.

"Given the health, economic and social consequences of influenza epidemics, the work of Dr. Zhou and her team demonstrates the importance of building influenza research capacity in Canada," said Dr. Bhagirath Singh, Scientific Director of the CIHR Institute of Infection and Immunity.

"Their research findings may help to develop new influenza treatments and prevent the disease, as well as add to global pandemic preparedness research."

To survive, the influenza virus hijacks the host animal or human's cellular machinery and forces it to make more copies of the virus. The researchers believe that the cellular events involved in this process are an excellent target for interventions against influenza.

The study revealed novel characteristics of a protein, called NS1, that activates a key pathway in the virus's reproduction. This information will help the researchers learn how to create harmless influenza viruses that can be used as live vaccines.

The pathway can be thought of as an assembly line with a switch to turn it on, says Zhou. "If the switch is turned on, the pathway enables efficient production of more viruses. But only the NS1 protein can turn on the switch."

The researchers are investigating genes and proteins of the influenza viruses of swine, horses and birds to see how they activate downstream cellular signalling pathways. To do this, they are using reverse genetics technology, where researchers begin with a gene and figure out its function.

These studies will allow the team to identify the genes that enable the virus to cause disease, laying the groundwork for antiviral drug development.

"Increasingly, new diseases involve both humans and animals," said Andrew Potter,VIDO's Associate Director (Research). "VIDO's background in veterinary research means that when diseases like avian influenza develop, we have the resources to begin studying the disease fairly quickly."

Support for Zhou and program members Yeun-Kyung Shin, Babiuk, Aleksandar Masic and Yang Li is provided by the Canadian Institutes of Health Research (CIHR) through a recently announced Pilot Project Grant for New Investigators in Infection and Immunity. The Saskatchewan Chicken Industry Development Fund and the Government of Saskatchewan are additional supporters. Shin is funded by the Veterinary Research and Quarantine Service of South Korea.

Background

According to World Health Organization estimates, influenza causes 36,000 deaths annually in the U.S. alone, and from 500,000 to one million around the world. The direct economic impact of influenza according to the U.S. Congress is an estimated $1 to 3 billion in the U.S., with as much as $15 billion in lost earnings. Avian influenza has raised the spectre of a new, potentially devastating human influenza pandemic in the future. In some countries, new strains of avian influenza are causing as much as 76 per cent mortality in humans.

VIDO (http://www.vido.org) is a world leader in the research and development of vaccine and immunotherapeutic technologies for livestock and humans. VIDO is a non-profit organization owned by the University of Saskatchewan. It collaborates extensively with external institutes and companies and provides a rich training environment.

The CIHR (http://www.cihr-irsc.gc.ca) is the Government of Canada's agency for health research with a mission is to create new scientific knowledge and to catalyze its translation into improved health, more effective health services and products, and a strengthened Canadian health care system. Composed of 13 institutes, CIHR provides leadership and support to more than 10,000 health researchers and trainees across Canada. The Institute of Infection and Immunity seeks to establish national leadership, priorities and programs that promote innovative research to reduce the global burden of infection and immune-based disease and improve quality of life.