This article is more than 5 years old. Information may no longer be current.
Study identifies mutations leading to influenza resistance
Click Here to Manage Email Alerts
Two mutations in the neuraminidase gene have been noted in oseltamivir-resistant strains of seasonal influenza, according to a study.
Researchers from the California Institute of Technology noted the molecular changes that led to resistance oseltamivir (Tamiflu, Genentech) among all strains of the seasonal influenza virus in Science magazine.
In 1998, it was first noted that a mutation, H274Y, was related to resistant strains of influenza. H274Y was initially relatively frail and grew poorly in both cultures and in animals. However, by 2007-2008, an outbreak of the H274Y mutation had spread worldwide.
The mutated neuraminidase protein was able to detect sialic acid from oseltamivir and replace amino acids, which caused a slight configurational change in a crucial region of the protein’s structure. The change of the neuraminidase protein’s formation caused the protein to no longer be able to bind to oseltamivir and thus permitted the escape of more viruses.
The researchers began their study by determining the power of the H274Y mutation upon the growth and spread of a virus. They hypothesized that the resistant mutation was an incidental effect preventing neuraminidase from reaching the cell membrane.
The assessment of the influenza sequences showed that two secondary mutations had appeared before the spread of the H274Y mutation. Researchers said that these preadaptive mutations enabled the survival and spread of the H274Y mutation.
The findings will be influential in the decision of which viral lineages should be closely monitored for signs of future drug-resistance, according to a press release.
Bloom JD. Science. 2010; 328:1272-1275.