Scientists examine bird flu infections to monitor for 'pandemic' mutations

Scientists funded by the Wellcome Trust are to examine what is preventing the H5N1 avian influenza virus from causing a human pandemic and what mutations are required to realise its deadly potential. The research could hold the key to early identification of a potential influenza pandemic, and to developing drugs and a vaccine.

Since its reappearance in 1997, the H5N1 influenza virus has caused disease and death in millions of birds around the globe. The number of infections in humans is still relatively small, however: from 2003 to the end of June 2008 there had been 385 known cases in humans, 243 of them fatal(1). So far, there appear to have been very few cases of human-to-human transmission.

Professor Ten Feizi at Imperial College London believes one reason why H5N1 has not yet evolved into an effective pathogen capable of widespread transmission between humans lies in how the virus attaches itself to the respiratory tract. She is leading an international research project which has received over £720,000 from the Wellcome Trust to identify the receptor molecules in the human respiratory tract to which viruses attach and to look at how changes in the binding protein on the surface of the virus might increase its ability to attach to the tract and cause infection.

Professor Feizi will work with Professors Menno de Jong and Jeremy Farrar from the Wellcome Trust's South East Asia Programme in Vietnam, Dr Alan Hay and Dr Steve Gamblin at the Medical Research Council National Institute for Medical Research, London, and Dr Mikhail Matrosovich at the Philipps University of Marburg, Germany.

"Over the last few years particularly in Asia we have seen just how deadly the H5N1 virus can be," says Professor Farrar from the Oxford University Clinical Research Unit in Ho Chi Minh City, Vietnam, where a number of people have been treated for infection by the virus. "So far, we have been relatively fortunate and there has been only limited evidence of the virus transmitting from human to human. The more we understand about the virus, how it interacts with the body, the better we will be prepared for any serious mutations that may arise."

In humans, influenza infection occurs via the respiratory tract, or airway. In order to cause disease, the virus must enter the body's cells where it can replicate and spread, but it must first find a site to which it can attach, known as a receptor. The virus can only attach to and enter the cells if the receptor fits into the binding proteins, or haemagglutinins (the "H" in H5N1), on the surface of the virus.