Volume 23, Number 4—April 2017
Antiviral Drug–Resistant Influenza B Viruses Carrying H134N Substitution in Neuraminidase, Laos, February 2016
|Virus name, passage history§
||Amino acid change in virus genes†
||Date specimen collected
HA, hemagglutinin; ILI, influenza-like illness; M1, matrix protein 1; NA, neuraminidase; NS1, nonstructural protein 1; SARI, severe acute respiratory illness; –, indicates same amino acid residue as in the consensus sequence of B-Victoria viruses that were circulating in Laos during the 2015‒16 influenza season.
†Strain-specific amino acid sequence numbering is used. Sequences for all 8 gene segments were generated using the MiSeq sequencing system (Illumina Inc., San Diego, CA, USA) (14) (Technical Appendix Table 1). Data are amino acid differences in protein-coded regions of NA, HA, M1, and NS1 genes compared with the consensus sequence. Not shown: synonymous nucleotide mutations that were common for the NA-H134N viruses: PB1-c93t, PB1-g1930a, and HA-g1520a. In addition, NA-H134N viruses differed from each other by the following synonymous nucleotide mutations: B/Laos/0406/2016 possessed NS1-g345a, B/Laos/0525/2016 possessed NA-t762a, NS1-a561g, and B/Laos/0654/2016 possessed NS2-g186a.
‡Corresponds to position 219 in NS1 protein numbering used by Ma et al. (15).
§Original indicates specimen collected from patient; C1 and C2 indicates virus propagated once or 2 times on MDCK cells.
¶Presence of the NA-H134N substitution in the original respiratory specimens was confirmed by a pyrosequencing assay (see Figure 1) (Technical Appendix Table 2).
- Burnham AJ, Baranovich T, Govorkova EA. Neuraminidase inhibitors for influenza B virus infection: efficacy and resistance. Antiviral Res. 2013;100:520–34.
- Budd A, Blanton L, Kniss K, Smith S, Mustaquim D, Davlin SL, et al. Update: influenza activity—United States and worldwide, May 22–September 10, 2016. MMWR Morb Mortal Wkly Rep. 2016;65:1008–14.
- Davlin SL, Blanton L, Kniss K, Mustaquim D, Smith S, Kramer N, et al. Influenza activity—United States, 2015–16 season and composition of the 2016–17 influenza vaccine. MMWR Morb Mortal Wkly Rep. 2016;65:567–75.
- Okomo-Adhiambo M, Mishin VP, Sleeman K, Saguar E, Guevara H, Reisdorf E, et al. Standardizing the influenza neuraminidase inhibition assay among United States public health laboratories conducting virological surveillance. Antiviral Res. 2016;128:28–35.
- World Health Organization. Meetings of the WHO working group on surveillance of influenza antiviral susceptibility – Geneva, November 2011 and June 2012. Wkly Epidemiol Rec. 2012;87:369–74.
- Colman PM, Hoyne PA, Lawrence MC. Sequence and structure alignment of paramyxovirus hemagglutinin-neuraminidase with influenza virus neuraminidase. J Virol. 1993;67:2972–80.
- Kawai N, Ikematsu H, Iwaki N, Maeda T, Satoh I, Hirotsu N, et al. A comparison of the effectiveness of oseltamivir for the treatment of influenza A and influenza B: a Japanese multicenter study of the 2003-2004 and 2004-2005 influenza seasons. Clin Infect Dis. 2006;43:439–44.
- Monto AS, McKimm-Breschkin JL, Macken C, Hampson AW, Hay A, Klimov A, et al. Detection of influenza viruses resistant to neuraminidase inhibitors in global surveillance during the first 3 years of their use. Antimicrob Agents Chemother. 2006;50:2395–402.
- Sugaya N, Mitamura K, Yamazaki M, Tamura D, Ichikawa M, Kimura K, et al. Lower clinical effectiveness of oseltamivir against influenza B contrasted with influenza A infection in children. Clin Infect Dis. 2007;44:197–202.
- Sheu TG, Deyde VM, Garten RJ, Klimov AI, Gubareva LV. Detection of antiviral resistance and genetic lineage markers in influenza B virus neuraminidase using pyrosequencing. Antiviral Res. 2010;85:354–60.
- Takashita E, Meijer A, Lackenby A, Gubareva L, Rebelo-de-Andrade H, Besselaar T, et al. Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2013-2014. Antiviral Res. 2015;117:27–38.
- Little K, Leang SK, Butler J, Baas C, Harrower B, Mosse J, et al. Zanamivir-resistant influenza viruses with Q136K or Q136R neuraminidase residue mutations can arise during MDCK cell culture creating challenges for antiviral susceptibility monitoring. Euro Surveill. 2015;20:30060.
- Centers for Disease Control and Prevention. Human influenza virus real-time RT-PCR detection and characterization panel. 510(k) summary. 2008. http://www.accessdata.fda.gov/cdrh_docs/pdf8/k080570.pdf.
- Zhou B, Donnelly ME, Scholes DT, St George K, Hatta M, Kawaoka Y, et al. Single-reaction genomic amplification accelerates sequencing and vaccine production for classical and Swine origin human influenza a viruses. J Virol. 2009;83:10309–13.
- Ma LC, Guan R, Hamilton K, Aramini JM, Mao L, Wang S, et al. A second RNA-binding site in the NS1 protein of influenza B virus. Structure. 2016;24:1562–72.