A novel neuraminidase deletion mutation conferring resistance to oseltamivir in clinical influenza A/H3N2 virus

Abstract

Neuraminidase (NA) mutations responsible for influenza resistance to oseltamivir vary according to the NA subtype; in influenza A/H3N2 viruses, NA-gene mutations occur predominantly at codons E119 and R292. In an oseltamivir-resistant influenza A/H3N2 virus isolated from an immunocompromised child after 107 days of cumulative treatment, the NA gene contained 3 aa substitutions (N146K, S219T, and A272V) and a 4-aa deletion (Del245-248); reversion mutation experiments using recombinant NA proteins determined that the deletion was the sole change responsible for resistance to oseltamivir. This study highlights the diversity of mechanisms of resistance to oseltamivir in clinical settings, reinforcing the need for novel anti-influenza strategies.