Avian influenza viruses do not achieve replication efficiently in humans without first acquiring adaptive mutations. This study identified an amino acid residue in H5N1 avian influenza viruses that allows them to efficiently replicate in a mouse model system.

Whether H5N1 viruses can and will acquire the ability to efficiently transmit among humans is a key concern, because such adaptation could lead to a pandemic. For this reason, our discovery is of great interest.

  Could you summarize the significance of your paper in layman’s terms?

The risk to humans of being infected by avian influenza viruses is generally low, because these viruses usually do not infect humans. The H5N1 avian influenza virus is one of a few avian influenza viruses that have crossed the species barrier to infect humans, often with deadly consequences.

To date, H5N1 virus spread from person to person has been limited. However, since all influenza viruses have the ability to change, researchers are concerned that the H5N1 virus could, at some point, become capable of infecting humans more easily and spreading from person to person. In this event, a pandemic (worldwide outbreak of disease) could occur.

Through our research, we have identified a specific change in H5N1 viruses that allows them to grow well in humans. Identification of this change, and others like it, means that we can look for such changes in circulating H5N1 strains and other avian influenza viruses to see if they have the potential to grow well in humans and to cause a pandemic. Action can then be taken to limit the spread of such viruses.

  How did you become involved in this research, and were there any obstacles along the way?

We noticed that 17 H5N1 viruses isolated from humans during the 1997 outbreak in Hong Kong could be divided into two groups based on their virulence in mice and that the degree of virulence correlated with the severity of disease in patients from whom the viruses were isolated. This observation intrigued us and prompted our group to determine the molecular basis of this difference in virulence. Because the methodologies involved in these studies are well established in my laboratory, we did not encounter much difficulty with this work.

  Are there any social or political implications for your research?

An influenza pandemic would lead to a staggering human death toll and likely paralyze society. It is, therefore, critical to identify, as early as possible, any changes in H5N1 avian viruses that might suggest that the virus is acquiring the ability to efficiently grow in humans. Our research identified one such mutation.