Genetic characterization of influenza B virus and oseltamivir resistance in pediatric patients with acute respiratory infections: a cross-sectional study.

Abstract

Influenza virus neuraminidase inhibitors (NAIs) drug usage can result in NAI resistance, especially in children and individuals with weakened immune systems. The aim of the present study was to identify NAI-resistant variants of IBV and to introduce probable novel mutations, phylogenetic study, and its epitope mapping based on NA gene in patients from Shiraz, Iran. A cross-sectional study was conducted between 2017 and 2018 on symptomatic children. A real-time PCR was run for IBV screening. Then, making use of direct sequencing, amplified 1401 bases of NA gene and phylogenetic tree reconstructed. Epitopes were predicted using ABCpred server. From among a total of 235 specimens, 9.7% were identified with IBV infection. Of them, sequence of NA gene for 17 isolates were analyzed. Phylogenetic analysis showed that 15 isolates belonged to Yamagata clade 3 Wisconsin/01-like subclade and 2 were related to Victoria clade 1 Brisbane/60-like subclade (Vic-1A-2). NA gene sequence analysis showed a total of 52 substitutions in which 27 were for B_Vic and 37 were for B_Yam isolates and 19 were novel substitutions. Only one substitution (S198N) was found in NA active site and T49M, I120V, N198S, N219K, S295R, D320K N340D, E358K, D384G, and D463N were found as probable resistance variants to NAIs. Epitope mapping showed some major differences in our isolates NA gene. Present study was one of the rare comprehensive studies conducted in Shiraz/Iran on IBV resistant associated variants to NAIs. We reported 11.7% mutation in NA active site and some probable NAIs resistant mutations. Epitope mapping confirmed major changes in NA gene which needs broader studies to confirm.