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Volume 23, Number 4—April 2017

Antiviral Drug–Resistant Influenza B Viruses Carrying H134N Substitution in Neuraminidase, Laos, February 2016

Tatiana Baranovich, Phengta Vongphrachanh, Pakapak Ketmayoon, Thongchanh Sisouk, Khampheng Chomlasack, Viengphone Khanthamaly, Ha Thuy Nguyen, Vasiliy P. Mishin, Henju Marjuki, John Barnes, Rebecca J. Garten, James Stevens, David Wentworth, and Larisa GubarevaComments to Author 
Author affiliations: Carter Consulting, Inc., Atlanta, Georgia, USA (T. Baranovich); World Health Organization Collaborating Center for Surveillance, Epidemiology and Control of Influenza, Atlanta (T. Baranovich, V. Khanthamaly, H.T. Nguyen, V.P. Mishin, H. Marjuki, J.R. Barnes, R.J. Garten, J. Stevens, D.E. Wentworth, L.V. Gubareva); Centers for Disease Control and Prevention, Atlanta (T. Baranovich, V. Khanthamaly, H.T. Nguyen, V.P. Mishin, H. Marjuki, J.R. Barnes, R.J. Garten, J. Stevens, D.E. Wentworth, L.V. Gubareva); National Center for Laboratory and Epidemiology, Vientiane, Laos (P. Vongphrachanh, P. Ketmayoon, T. Sisouk, K. Chomlasack); World Health Organization Emerging Disease Surveillance and Response Unit, Vientiane, Laos (P. Ketmayoon); Battelle Memorial Institute, Atlanta (H.T. Nguyen)

Main Article

Table 1

Neuraminidase inhibitor susceptibility of influenza B viruses isolated from human respiratory specimens. Laos, 2016*

Virus isolate
NA amino acid change§
Mean IC50 ± SD, nmol/L (fold change)†‡
Date specimen collected
GISAID accession no.
B/Laos/0080/2016 H134 1.09 ± 0.16 (1) 14.48 ± 1.76 (1) 0.36 ± 0.05 (1) 1.15 ± 0.02 (1) 14 Jan EPIISL 222862
B/Laos/0406/2016 H134N 148.36 ± 14.40 (129) 37.87 ± 1.96 (4) 31.09 ± 3.70 (74) 62.43 ± 4.66 (42) 9 Feb EPIISL 230596
B/Laos/0525/2016 H134N 176.03 ± 11.14 (158) 37.55 ± 5.60 (4) 30.25 ± 2.90 (72) 60.12 ± 2.38 (41) 15 Feb EPIISL 230599
B/Laos/0654/2016 H134N 151.95 ± 16.30 (138) 35.06 ± 5.08 (4) 31.29 ± 0.24 (75) 61.53 ± 1.03 (42) 25 Feb EPIISL 230600

*Viruses were isolated and propagated on MDCK cells. Susceptibility was determined using a fluorescence-based neuraminidase (NA) inhibition assay.
†IC50 values (NA inhibitor concentration needed to reduce NA activity by 50%) represent mean ± SD from 3 independent experiments.
‡Fold change compared with the median IC50 value determined for influenza B-Victoria lineage viruses (n = 430) that were circulating worldwide during the 2015‒16 influenza season. Median IC50 values are 1.11, 9.67, 0.42, and 1.47 nM for zanamivir, oseltamivir, peramivir, and laninamivir, respectively. Bold indicates fold increases that correspond to reduced inhibition (5- to 50-fold) or to highly reduced (>50-fold) inhibition by a NAI, as outlined by the World Health Organization Expert Working Group of the Global Influenza Surveillance and Response System for Surveillance on Antiviral Susceptibility (5).
§Amino acid residue 134 in influenza type B NA corresponds to residue Q136 in N1 and N2 NA amino acid numbering (6).
¶Oseltamivir carboxylate was used in NA inhibition assay.

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  1. Burnham  AJ, Baranovich  T, Govorkova  EA. Neuraminidase inhibitors for influenza B virus infection: efficacy and resistance. Antiviral Res. 2013;100:52034. DOIPubMedGoogle Scholar
  2. 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;65:100814. DOIPubMedGoogle Scholar
  3. 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;65:56775. DOIPubMedGoogle Scholar
  4. 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;128:2835. DOIPubMedGoogle Scholar
  5. 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;87:36974.PubMedGoogle Scholar
  6. Colman  PM, Hoyne  PA, Lawrence  MC. Sequence and structure alignment of paramyxovirus hemagglutinin-neuraminidase with influenza virus neuraminidase. J Virol. 1993;67:297280.PubMedGoogle Scholar
  7. 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;43:43944. DOIPubMedGoogle Scholar
  8. 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;50:2395402. DOIPubMedGoogle Scholar
  9. 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;44:197202. DOIPubMedGoogle Scholar
  10. 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;85:35460. DOIPubMedGoogle Scholar
  11. 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;117:2738. DOIPubMedGoogle Scholar
  12. 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. DOIPubMedGoogle Scholar
  13. Centers for Disease Control and Prevention. Human influenza virus real-time RT-PCR detection and characterization panel. 510(k) summary. 2008.
  14. 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;83:1030913. DOIPubMedGoogle Scholar
  15. 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;24:156272. DOIPubMedGoogle Scholar

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