Background: Influenza is a severe respiratory viral infection that causes significant morbidity and mortality, due to annual epidemics and unpredictable pandemics. At present, drugs used in influenza virus B infection treatment are mainly neuraminidase inhibitors (NAIs). With the extensive use of NAI drugs, the influenza virus B has carried different drug-resistant mutations. This study aims to analyze the drug resistance mutations of the NA sequence in Flu B and provide guidance for clinical medication.
Methods: Near full-length sequences of the NA region of all influenza B viruses from January 1, 2006 to December 31, 2018 were downloaded from public databases GISAID and NCBI. Multiple sequence alignments were performed using Clustal Omega 1.2.4 software. Subsequently, phylogenetic trees were constructed by FastTree 2.1.11 and clustered by ClusterPickergui_1.2.3.JAR. Then, the major drug resistance sites and surrounding auxiliary sites were analyzed by Mega-X and Weblogo (http://weblogo.threeplusone.com/) tools.
Results: Among the amino acid sequences of neuraminidase (NA) from 2006 to 2018, only Cluster 4 in 2018 carried D197N mutation of NA active site, while other drug resistance sites were conserved without mutation. According to the Weblogo analysis, a large number of N198, S295, K373, and K375 mutations were found in the amino acid residues at the auxiliary sites surround D197, N294, and R374 in the influenza B virus.
Conclusion: We found the D197N mutation in Cluster 4 of the 2018 influenza B virus, with a large number of N198, S295, K373, and K375 mutations in the helper sites around N197, N294, R374 from 2006 to 2018. NA inhibitors are currently the only kind of specific antiviral agent for the influenza B virus, although these mutations cause mild NAIs resistance.