Once they selected the isolates for study, the researchers used powerful supercomputers to analyze the evolution of these proteins and their various mutations. The computational power allows them to match similar regions on the proteins and put the mutation data into context in time and geography.
One result of these computations is called a phylogenetic tree, which documents the history of mutations including those that cause drug resistance. Phylogenetics is the study of the evolutionary relationships and features among various biological species, genes or proteins that share a common ancestor.
In tracing the history of neuraminidase in pandemic and seasonal H1N1, the group found that mutations in the same amino acid position in both seasonal and pandemic H1N1 drove the viruses toward resistance to antivirals.
"Basically a change in the amino acid changes how the neuraminidase protein folds, and the molecule in Tamiflu no longer has the ability to interfere with the virus," Janies said.
The researchers also used a technique in which they compared different types of mutations those that do cause antiviral resistance and others that don't have that effect to see which type of mutation is more common.
"We look at the ratio of mutations that do confer resistance vs. those that don't, and if the ratio is higher than 1, it means that change is being promoted by natural selection rather than chance. Something is driving the evolution of drug resistance," Janies said. "We could see that happening in seasonal influenza and in the data we have so far for pandemic influenza, as well.
"A Darwinian would say that something changed that made the Tamiflu-resistant strain more fit than the wild type," he said.
The group also examined mutations that alter these two strains of H1N1 viruses' responses to Relenza. Resistance to that drug is relatively rare, Janies said, which could be attributed to l
|Contact: Daniel Janies|
Ohio State University