Identification of a permissive secondary mutation that restores the enzymatic activity of oseltamivir resistance mutation H275Y.
Abstract
The potential for influenza A virus (IAV) to cause pandemics makes understanding evolutionary mechanisms that impact drug resistance critical for developing surveillance and treatment strategies. Oseltamivir is the most widely used therapeutic strategy to treat IAV infections, but mutations in IAV can lead to drug resistance. The main oseltamivir resistance mutation, H275Y, occurs in the neuraminidase (NA) protein of IAV and reduces drug binding as well as NA function. Here, we identify a new helper mutation, Y276F that can rescue the functional defects of H275Y and contribute to the evolution of drug resistance in IAV.