A novel I221L substitution in neuraminidase confers high-level resistance to oseltamivir in influenza B viruses.

ABSTRACT:

Unlabelled

Influenza B viruses with a novel I221L substitution in neuraminidase (NA) conferring high-level resistance to oseltamivir were isolated from an immunocompromised patient after prolonged oseltamivir treatment.

Methods

Enzymatic characterization of the NAs (Km, Ki) and the in vitro fitness of viruses carrying wild-type or mutated (I221L) NA genes were evaluated. Proportions of wild-type and mutated NA genes were directly quantified in the patient samples. Structural characterizations by X-ray crystallography of a wild-type and I221L variant NA were performed.

Results

The Km and Ki revealed that the I221L variant NA had approximately 84 and 51 times lower affinity for oseltamivir carboxylate and zanamivir, respectively, compared with wild-type NA. Viruses with

SUBMITTER: Escuret V 

PROVIDER: S-EPMC4176448 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature