Mutations in H5N1 avian influenza viruses

Several recent media reports have included speculations about the significance of mutations in H5N1 avian influenza viruses. Some reports have suggested that the likelihood of another pandemic may have increased as a result of changes in the virus.

Since 1997, when the first human infections with the H5N1 avian influenza virus were documented, the virus has undergone a number of changes.

These changes have affected patterns of virus transmission and spread among domestic and wild birds. They have not, however, had any discernible impact on the disease in humans, including its modes of transmission. Human infections remain a rare event. The virus does not spread easily from birds to humans or readily from person to person.

Influenza viruses are inherently unstable. As these viruses lack a genetic proof-reading mechanism, small errors that occur when the virus copies itself go undetected and uncorrected. Specific mutations and evolution in influenza viruses cannot be predicted, making it difficult if not impossible to know if or when a virus such as H5N1 might acquire the properties needed to spread easily and sustainably among humans. This difficulty is increased by the present lack of understanding concerning which specific mutations would lead to increased transmissibility of the virus among humans.

Virtually all the known subtypes of influenza A viruses circulate in some wild birds, most notably wild waterfowl. In these birds, different viruses constantly mingle with each other and frequently exchange genetic material, resulting in a huge pool of constantly changing viruses. Mutations and reassortment events are commonly observed in the affected bird populations.

In animals, some recent evolutionary changes in the H5N1 virus appear to have made control efforts more difficult and further international spread of the virus in birds more likely. Such changes are fully understandable, particularly in view of the exceptionally large number of birds that have been infected with the H5N1 virus and the frequent interactions between infected free-ranging poultry and wild waterfowl.

Studies have shown that H5N1 viruses from the current outbreaks, when compared with viruses from 1997 and 2003, have become progressively more lethal in experimentally infected chickens and mice, and are also hardier, surviving several days longer in the environment. Other studies have shown that the virus is not yet fully adapted to poultry and is continuing to evolve.

Domestic ducks have acquired an ability to resist the disease caused by some strains, and are now capable of excreting large quantities of highly pathogenic virus without showing the warning signs of illness. In endemic countries, this altered role of domestic ducks is now thought to contribute to perpetuation of the transmission cycle. Research conducted in South-east Asia has recently shown that multiple distinct lineages of H5N1 virus have become established in poultry in different geographical regions, indicating the long- term endemicity of the virus in parts of Asia. That research also detected highly pathogenic H5N1 virus in apparently healthy migratory birds.