Skip to main content
Top
Published in: Virology Journal 1/2015

Open Access 01-12-2015 | Research

Characteristics of oseltamivir-resistant influenza A (H1N1) pdm09 virus during the 2013–2014 influenza season in Mainland China

Authors: Weijuan Huang, Xiyan Li, Yanhui Cheng, Minju Tan, Junfeng Guo, Hejiang Wei, Xiang Zhao, Yu Lan, Ning Xiao, Zhao Wang, Dayan Wang, Yuelong Shu

Published in: Virology Journal | Issue 1/2015

Login to get access

Abstract

Background

In this study, we analyzed the characteristics of oseltamivir-resistant influenza A (H1N1) pdm09 virus isolated from patients in mainland China during the influenza season from September 2013 through March 2014, and provide guidance on which antiviral to be used for clinical treatment.

Methods

The all viruses collected from September 1, 2013 through March 31, 2014 were obtained from the Chinese National Influenza Surveillance Network. A fluorescence-based assay was used to detect virus sensitivity to neuraminidase inhibitors (NAIs). The hemagglutinin (HA) and neuraminidase (NA) gene of the oseltamivir-resistant viruses were sequenced.

Results

A total of 24 (2.14 %) influenza A (H1N1) pdm09 viruses that were resistant to oseltamivir were identified. These 24 viruses were isolated from 23 patients and no epidemiological link among them could be identified. Except for one virus with the H275H/Y mixture substitution, all the other 23 viruses had H275Y substitution in the NA protein. Sequence analysis revealed that the amino acid substitutions in the HA protein of influenza A (H1N1) pdm09 viruses with H275Y substitution isolated from mainland China were similar to the viruses from clustered cases reported in the United States, and the amino acid substitutions in the NA protein were similar to the viruses reported in Sapporo, Japan in 2013–2014. All of the oseltamivir-resistant viruses in mainland China and Japan possessed additional substitutions N386K, V241I and N369K in the NA protein, while most (>89 %) resistant-viruses from the United States during the same period possess V241I and N369K and did not have the N386K substitution. The N386K substitution was also exist in most sensitive viruses during the same period in mainland China. The amino acid substitutions in both HA and NA protein differed from the clustered cases from Australia reported in 2011 with additional substitutions. The drug-resistant influenza A(H1N1) pdm09 viruses were from patients without any known NAIs medication history prior to sampling.

Conclusions

During the influenza season from September 2013 through March 2014 in Mainland China, oseltamivir-resistant influenza A(H1N1)pdm09 viruses were much more frequently detected than ever since the appearance of the virus in 2009.
Appendix
Available only for authorised users
Literature
1.
go back to reference Ling LM, Chow AL, Lye DC, Tan AS, Krishnan P, Cui L, et al. Effects of early oseltamivir therapy on viral shedding in 2009 pandemic influenza A (H1N1) virus infection. Clin Infect Dis. 2010;50:963–9.PubMedCrossRef Ling LM, Chow AL, Lye DC, Tan AS, Krishnan P, Cui L, et al. Effects of early oseltamivir therapy on viral shedding in 2009 pandemic influenza A (H1N1) virus infection. Clin Infect Dis. 2010;50:963–9.PubMedCrossRef
2.
go back to reference Campbell CN, Mytton OT, McLean EM, Rutter PD, Pebody RG, Sachedina N, et al. Hospitalization in two waves of pandemic influenza A(H1N1) in England. Epidemiol Infect. 2010;139:1560–9.PubMedCrossRef Campbell CN, Mytton OT, McLean EM, Rutter PD, Pebody RG, Sachedina N, et al. Hospitalization in two waves of pandemic influenza A(H1N1) in England. Epidemiol Infect. 2010;139:1560–9.PubMedCrossRef
3.
go back to reference Meijer A, Rebelo-de-Andrade H, Correia V, Besselaar T, Drager-Dayal R, Fry A, et al. Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2012–2013. Antiviral Res. 2014;110:31–41.PubMedCrossRef Meijer A, Rebelo-de-Andrade H, Correia V, Besselaar T, Drager-Dayal R, Fry A, et al. Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2012–2013. Antiviral Res. 2014;110:31–41.PubMedCrossRef
4.
go back to reference Gubareva LV, Kaiser L, Hayden FG. Influenza virus neuraminidase inhibitors. Lancet. 2000;355:827–35.PubMedCrossRef Gubareva LV, Kaiser L, Hayden FG. Influenza virus neuraminidase inhibitors. Lancet. 2000;355:827–35.PubMedCrossRef
5.
go back to reference Takashita E, Kiso M, Fujisaki S, Yokoyama M, Nakamura K, Shirakura M, et al. Characterization of a large cluster of influenza A(H1N1)pdm09 virus cross-resistant to oseltamivir and peramivir during the 2013/2014 influenza season in Japan. Antimicrob Agents Chemother. 2015;59:2607–17. pii:AAC.04836-14.PubMedCrossRef Takashita E, Kiso M, Fujisaki S, Yokoyama M, Nakamura K, Shirakura M, et al. Characterization of a large cluster of influenza A(H1N1)pdm09 virus cross-resistant to oseltamivir and peramivir during the 2013/2014 influenza season in Japan. Antimicrob Agents Chemother. 2015;59:2607–17. pii:AAC.04836-14.PubMedCrossRef
6.
go back to reference WHO/Meetings of the WHO working group on surveillance of influenza antiviral susceptibility-Geneva. November 2011and June 2012. Wkly Epidemiol Rec (WER). 2012; 87: 369–374. WHO/Meetings of the WHO working group on surveillance of influenza antiviral susceptibility-Geneva. November 2011and June 2012. Wkly Epidemiol Rec (WER). 2012; 87: 369–374.
7.
go back to reference Okomo-Adhiambo M, Fry AM, Su S, Nguyen HT, Elal AA, Negron E, et al. Oseltamivir-resistant influenza A(H1N1)pdm09 viruses, United States, 2013–14. Emerg Infect Dis. 2015;21:136–41.PubMedCentralPubMedCrossRef Okomo-Adhiambo M, Fry AM, Su S, Nguyen HT, Elal AA, Negron E, et al. Oseltamivir-resistant influenza A(H1N1)pdm09 viruses, United States, 2013–14. Emerg Infect Dis. 2015;21:136–41.PubMedCentralPubMedCrossRef
8.
go back to reference Hurt AC, Hardie K, Wilson NJ, Deng YM, Osbourn M, Leang SK, et al. Characteristics of a widespread community cluster of H275Y oseltamivir-resistant A(H1N1)pdm09 influenza in Australia. J Infect Dis. 2012;206:148–57.PubMedCentralPubMedCrossRef Hurt AC, Hardie K, Wilson NJ, Deng YM, Osbourn M, Leang SK, et al. Characteristics of a widespread community cluster of H275Y oseltamivir-resistant A(H1N1)pdm09 influenza in Australia. J Infect Dis. 2012;206:148–57.PubMedCentralPubMedCrossRef
9.
10.
go back to reference Chutinimitkul S, Herfst S, Steel J, Lowen AC, Ye J, van Riel D, et al. Virulence-associated substitution D222G in the hemagglutinin of 2009 pandemic influenza A(H1N1) virus affects receptor binding. J Virol. 2010;84:11802–13.PubMedCentralPubMedCrossRef Chutinimitkul S, Herfst S, Steel J, Lowen AC, Ye J, van Riel D, et al. Virulence-associated substitution D222G in the hemagglutinin of 2009 pandemic influenza A(H1N1) virus affects receptor binding. J Virol. 2010;84:11802–13.PubMedCentralPubMedCrossRef
11.
go back to reference Liu Y, Childs RA, Matrosovich T, Wharton S, Palma AS, Chai W, et al. Altered receptor specificity and cell tropism of D222G hemagglutinin mutants isolated from fatal cases of pandemic A(H1N1) 2009 influenza virus. J Virol. 2010;84:12069–74.PubMedCentralPubMedCrossRef Liu Y, Childs RA, Matrosovich T, Wharton S, Palma AS, Chai W, et al. Altered receptor specificity and cell tropism of D222G hemagglutinin mutants isolated from fatal cases of pandemic A(H1N1) 2009 influenza virus. J Virol. 2010;84:12069–74.PubMedCentralPubMedCrossRef
12.
go back to reference Zhang Y, Zhang Q, Gao Y, He X, Kong H, Jiang Y, et al. Keymolecular factors in hemagglutinin and PB2 contribute to efficient transmission of the 2009 H1N1 pandemic influenza virus. J Virol. 2012;86:9666–74.PubMedCentralPubMedCrossRef Zhang Y, Zhang Q, Gao Y, He X, Kong H, Jiang Y, et al. Keymolecular factors in hemagglutinin and PB2 contribute to efficient transmission of the 2009 H1N1 pandemic influenza virus. J Virol. 2012;86:9666–74.PubMedCentralPubMedCrossRef
13.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
14.
go back to reference Ginting TE, Shinya K, Kyan Y, Makino A, Matsumoto N, Kaneda S, et al. Amino acid changes in hemagglutinin contribute to the replication of oseltamivir-resistant H1N1 influenza viruses. J Virol. 2012;86:121–7.PubMedCentralPubMedCrossRef Ginting TE, Shinya K, Kyan Y, Makino A, Matsumoto N, Kaneda S, et al. Amino acid changes in hemagglutinin contribute to the replication of oseltamivir-resistant H1N1 influenza viruses. J Virol. 2012;86:121–7.PubMedCentralPubMedCrossRef
15.
go back to reference Butler J, Hooper KA, Petrie S, Lee R, Maurer-Stroh S, Reh L, et al. Estimating the fitness advantage conferred by permissive neuraminidase mutations in recent oseltamivir-resistant A(H1N1)pdm09 influenza viruses. PLoS Pathog. 2014;10(4):e1004065.PubMedCentralPubMedCrossRef Butler J, Hooper KA, Petrie S, Lee R, Maurer-Stroh S, Reh L, et al. Estimating the fitness advantage conferred by permissive neuraminidase mutations in recent oseltamivir-resistant A(H1N1)pdm09 influenza viruses. PLoS Pathog. 2014;10(4):e1004065.PubMedCentralPubMedCrossRef
16.
go back to reference Abed Y, Pizzorno A, Bouhy X, Rhéaume C, Boivin G. Impact of potential permissive neuraminidase mutations on viral fitness of the H275Y oseltamivir-resistant influenza A(H1N1)pdm09 virus in vitro, in mice and in ferrets. J Virol. 2014;88:1652–8.PubMedCentralPubMedCrossRef Abed Y, Pizzorno A, Bouhy X, Rhéaume C, Boivin G. Impact of potential permissive neuraminidase mutations on viral fitness of the H275Y oseltamivir-resistant influenza A(H1N1)pdm09 virus in vitro, in mice and in ferrets. J Virol. 2014;88:1652–8.PubMedCentralPubMedCrossRef
17.
go back to reference Takashita E, Ejima M, Itoh R, Miura M, Ohnishi A, Nishimura H, et al. A community cluster of influenza A(H1N1)pdm09 virus exhibiting cross-resistance to oseltamivir and peramivir in Japan, November to December 2013. Euro Surveill. 2014;19:1. Takashita E, Ejima M, Itoh R, Miura M, Ohnishi A, Nishimura H, et al. A community cluster of influenza A(H1N1)pdm09 virus exhibiting cross-resistance to oseltamivir and peramivir in Japan, November to December 2013. Euro Surveill. 2014;19:1.
18.
go back to reference Nguyen HT, Sheu TG, Mishin VP, Klimov AI, Gubareva LV. Assessment of pandemic and seasonal influenza A(H1N1) virus susceptibility to neuraminidase inhibitors in three enzyme activity inhibition assays. Antimicrob Agents Chemother. 2010;54:3671–7.PubMedCentralPubMedCrossRef Nguyen HT, Sheu TG, Mishin VP, Klimov AI, Gubareva LV. Assessment of pandemic and seasonal influenza A(H1N1) virus susceptibility to neuraminidase inhibitors in three enzyme activity inhibition assays. Antimicrob Agents Chemother. 2010;54:3671–7.PubMedCentralPubMedCrossRef
19.
go back to reference Okomo-Adhiambo M, Sleeman K, Ballenger K, Nguyen HT, Mishin VP, Sheu TG, et al. Neuraminidase inhibitor susceptibility testing in human influenza viruses: a laboratory surveillance perspective. Viruses. 2010;2:2269–89.PubMedCentralPubMedCrossRef Okomo-Adhiambo M, Sleeman K, Ballenger K, Nguyen HT, Mishin VP, Sheu TG, et al. Neuraminidase inhibitor susceptibility testing in human influenza viruses: a laboratory surveillance perspective. Viruses. 2010;2:2269–89.PubMedCentralPubMedCrossRef
Metadata
Title
Characteristics of oseltamivir-resistant influenza A (H1N1) pdm09 virus during the 2013–2014 influenza season in Mainland China
Authors
Weijuan Huang
Xiyan Li
Yanhui Cheng
Minju Tan
Junfeng Guo
Hejiang Wei
Xiang Zhao
Yu Lan
Ning Xiao
Zhao Wang
Dayan Wang
Yuelong Shu
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2015
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/s12985-015-0317-1

Other articles of this Issue 1/2015

Virology Journal 1/2015 Go to the issue