Helping the Resistance

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Science  04 Jun 2010:
Vol. 328, Issue 5983, pp. 1243-1244
DOI: 10.1126/science.1190994

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The evolution of antiviral drug resistance sounds like a simple Darwinian story. The high mutation rate that characterizes RNA viruses ensures that drug-resistant mutations are generated continuously, and the global use of antivirals provides the selection pressure for these mutations to sweep through viral populations. In some cases, however, reality is more complex. The mutations that confer antiviral resistance may have a detrimental effect on viral fitness in the absence of the drug so that secondary fitness-restoring mutations must occur to enable the large-scale spread of resistance. More puzzling, drug resistance can also occur in the absence of the main agent of selection—the widespread use of antiviral drugs. Both of these evolutionary conundrums are apparent in one of the most important cases of antiviral resistance in recent years—the global spread of resistance to oseltamivir in seasonal H1N1 influenza A virus. On page 1272 of this issue, Bloom et al. (1) show that in a “permissive” genetic background, seasonal H1N1 virus avoids the fitness costs normally associated with oseltamivir resistance.