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Study: Excessive use of antiviral drugs could aid deadly flu
Date:1/7/2009

rotein called the membrane ion channel, or the M2 protein. According to the computational comparison of the avian flu genomes, upwards of one-third of the strains contained a key mutation that changed the M2 protein in a way that allowed the virus to escape the inhibiting effects of adamantanes. To evade adamantanes, mutations can occur at several positions on the protein, suggesting that influenza can evolve in many ways to resist the drug.

The researchers also were able to demonstrate that the resistance developed as a result of natural selection, because the avian flu virus strains experienced mutations that changed the M2 protein to evade the drug more often than one would expect by chance. Sometimes, dramatic changes to the genetic code occur when diverse strains of viruses shuffle whole genes among themselves in a process called reassortment. The analysis determined that any reassortment that occurred in the H5N1 strains studied did not lead to drug resistance.

The study also showed that the mutation-mediated cases of drug resistance didn't start in just one strain of avian flu. One resistant strain originated in China and spread through Southeast Asia, while another strain that was originally susceptible to adamantanes spread to Indonesia and then independently developed resistance in that country. The Google Earth map offers a vivid visualization of exactly where in the world these resistant lineages originated and where they are spreading.

At the height of their popularity in China and Russia, adamantanes were added to over-the-counter cold medicines and were also given to animals in some agricultural settings.

"We don't have hard data on how it was used or whether it was appropriately or inappropriately used, but in general, people are putting a lot of antimicrobials into the environment now," Janies said. "When people do that, they change the selective landscape. The virus would rather remain in its wild type form, but
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Contact: Daniel Janies
Daniel.Janies@osumc.edu
614-292-1202
Ohio State University
Source:Eurekalert

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