Genetic Differences Between Potential Pandemic Influenza Strains

"As the virus continues its geographic expansion, it is also undergoing genetic diversity expansion," says Rebecca Garten, a researcher on the study. "Back in 2003 we only had one genetically distinct population of H5N1 with the potential to cause a human pandemic, now we have two."

Garten and her colleagues conducted a phylogenetic analysis of over 300 H5N1 virus samples taken from both avian and human sources from 2003 through the summer of 2005. They correlated the genetic makeup of viruses to the physical characteristics of viruses, including surface proteins and receptor sites, to determine where each virus should be placed on the H5N1 family tree.

Not all H5N1 viruses are genetically the same. Over the years researchers have identified different genetic groups called genotypes.

The majority of the viruses, including all the human cases, belonged to genotype Z. There were also small numbers of viruses isolated from avian populations that were genotype V or W or recently identified genotype G.

That is where the similarity between the two human strains ended. Previous research published by the World Health Organization has further classified genotype Z into subgroups called clades. In 2003 and 2004, clade 1 viruses were primarily responsible for outbreaks, including all infections in human, in Viet Nam, Cambodia and Thailand.

In 2005 a second strain of H5N1 began causing disease in humans in Indonesia. Analysis of the Indonesia strain found that it belongs to genotype Z clade 2, a subgroup of the virus that previously was not known to cause human disease. Clade 1 and clade 2 viruses may share the same ancestor but are different and can be be likened to cousins.

What this means, says Garten, is that the pool of H5N1 candidates with the potential to cause a human influenza pandemic is getting more genetically diverse, which makes studying the virus more complex and heightens the need for increased surveillance. She expects further continued diversity in the future.

"Change is the only constant. Only time will tell whether the virus evolves or mutates in such a way that it can be transmitted from human to human efficiently," says Garten.