title: Characteristics of oseltamivir-resistant influenza A (H1N1) pdm09 virus during the 2013-2014 influenza season in Mainland China.
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.
authors.affiliation: National Institute for Viral Disease Control and Prevention, China CDC, Key Laboratory for Medical Virology, National Health and Family Planning Commission, 155 Changbai Road, Changping District, Beijing, 102206, PR China. huangweijuan@cnic.org.cn.
authors.forename: Weijuan
authors.initials: W
authors.lastname: Huang
authors.affiliation: National Institute for Viral Disease Control and Prevention, China CDC, Key Laboratory for Medical Virology, National Health and Family Planning Commission, 155 Changbai Road, Changping District, Beijing, 102206, PR China. lixiyan@cnic.org.cn.
authors.forename: Xiyan
authors.initials: X
authors.lastname: Li
authors.affiliation: National Institute for Viral Disease Control and Prevention, China CDC, Key Laboratory for Medical Virology, National Health and Family Planning Commission, 155 Changbai Road, Changping District, Beijing, 102206, PR China. chengyanhui@cnic.org.cn.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: National Institute for Viral Disease Control and Prevention, China CDC, Key Laboratory for Medical Virology, National Health and Family Planning Commission, 155 Changbai Road, Changping District, Beijing, 102206, PR China. tanminju@cnic.org.cn.
authors.forename: Minju
authors.initials: M
authors.lastname: Tan
authors.affiliation: National Institute for Viral Disease Control and Prevention, China CDC, Key Laboratory for Medical Virology, National Health and Family Planning Commission, 155 Changbai Road, Changping District, Beijing, 102206, PR China. guojunfeng@cnic.org.cn.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Guo
authors.affiliation: National Institute for Viral Disease Control and Prevention, China CDC, Key Laboratory for Medical Virology, National Health and Family Planning Commission, 155 Changbai Road, Changping District, Beijing, 102206, PR China. weihejiang@cnic.org.cn.
authors.forename: Hejiang
authors.initials: H
authors.lastname: Wei
authors.affiliation: National Institute for Viral Disease Control and Prevention, China CDC, Key Laboratory for Medical Virology, National Health and Family Planning Commission, 155 Changbai Road, Changping District, Beijing, 102206, PR China. zhaoxiang@cnic.org.cn.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhao
authors.affiliation: National Institute for Viral Disease Control and Prevention, China CDC, Key Laboratory for Medical Virology, National Health and Family Planning Commission, 155 Changbai Road, Changping District, Beijing, 102206, PR China. lanyu@cnic.org.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: Lan
authors.affiliation: National Institute for Viral Disease Control and Prevention, China CDC, Key Laboratory for Medical Virology, National Health and Family Planning Commission, 155 Changbai Road, Changping District, Beijing, 102206, PR China. xiaoning@cnic.org.cn.
authors.forename: Ning
authors.initials: N
authors.lastname: Xiao
authors.affiliation: National Institute for Viral Disease Control and Prevention, China CDC, Key Laboratory for Medical Virology, National Health and Family Planning Commission, 155 Changbai Road, Changping District, Beijing, 102206, PR China. wangzhao@cnic.org.cn.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: National Institute for Viral Disease Control and Prevention, China CDC, Key Laboratory for Medical Virology, National Health and Family Planning Commission, 155 Changbai Road, Changping District, Beijing, 102206, PR China. dayanwang@cnic.org.cn.
authors.forename: Dayan
authors.initials: D
authors.lastname: Wang
authors.affiliation: National Institute for Viral Disease Control and Prevention, China CDC, Key Laboratory for Medical Virology, National Health and Family Planning Commission, 155 Changbai Road, Changping District, Beijing, 102206, PR China. yshu@cnic.org.cn.
authors.forename: Yuelong
authors.initials: Y
authors.lastname: Shu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D024882:Drug Resistance, Viral; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics; D006801:Humans; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000302:isolation & purification*; D007251:Influenza, Human / Q000821:virology*; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009439:Neuraminidase / Q000235:genetics; D053139:Oseltamivir / Q000494:pharmacology*; D017422:Sequence Analysis, DNA; D014764:Viral Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; C543345:H1N1 virus hemagglutinin; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D014764:Viral Proteins; D053139:Oseltamivir; C487630:NA protein, influenza A virus; D009439:Neuraminidase