title: Viral genome and antiviral drug sensitivity analysis of two patients from a family cluster caused by the influenza A(H7N9) virus in Zhejiang, China, 2013.
abstract: OBJECTIVE
  In the winter of 2013, people were facing the risk of human-to-human transmission of the re-emerging influenza A(H7N9) virus. We report herein information on the clinical features of two patients from the same family infected with this virus, the genomic sequences of the viruses harbored, and antiviral drug sensitivity.
  
  
  METHODS
  Clinical and epidemiological data of two patients from the same family were collected and analyzed. Sequencing was done for the viruses isolated from these two patients and one epidemiologically related chicken, and the sequences of the eight gene segments of the viruses were analyzed phylogenetically. The sensitivity of the viruses to antiviral drug treatment was determined by neuraminidase inhibitor susceptibility test.
  
  
  RESULTS
  The two patients from one family cluster shared the same symptoms but had different outcomes, and had a strong epidemiological link. Three strains, two from these two patients and one from the chicken, were isolated. Genome sequencing and analyses of phylogenetic trees demonstrated that the two viruses were almost identical. We noted the presence of the PB2 E627K amino acid substitution that was not present in isolates from the first wave, as well as two new mutations in the NA gene and six in the PB2 gene. Drug sensitivity testing showed that the new isolates were resistant to oseltamivir but sensitive to peramivir.
  
  
  CONCLUSIONS
  The two patients from one family cluster were probable human-to-human transmission cases. The new isolates were sensitive to peramivir but showed reduced sensitivity to oseltamivir.
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310031, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Hai Nv
authors.initials: HN
authors.lastname: Gao
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310031, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Hang Ping
authors.initials: HP
authors.lastname: Yao
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310031, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Wei Feng
authors.initials: WF
authors.lastname: Liang
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310031, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Xiao Xin
authors.initials: XX
authors.lastname: Wu
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310031, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Hai Bo
authors.initials: HB
authors.lastname: Wu
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310031, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Nan Ping
authors.initials: NP
authors.lastname: Wu
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310031, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Shi Gui
authors.initials: SG
authors.lastname: Yang
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310031, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310031, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Kun Kai
authors.initials: KK
authors.lastname: Su
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310031, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310031, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Shu Fa
authors.initials: SF
authors.lastname: Zheng
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310031, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Yi Xin
authors.initials: YX
authors.lastname: Zhu
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China; State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Hong Lin
authors.initials: HL
authors.lastname: Chen
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China; State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Kwok-Yung
authors.initials: KY
authors.lastname: Yuen
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310031, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China. Electronic address: ljli@zju.edu.cn.
authors.forename: Lan Juan
authors.initials: LJ
authors.lastname: Li
mesh_terms: D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000494:pharmacology; D002681:China; D024882:Drug Resistance, Viral; D005260:Female; D016679:Genome, Viral; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D007251:Influenza, Human / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D053139:Oseltamivir / Q000494:pharmacology; D010802:Phylogeny
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir
keywords: Drug sensitivity; H7N9; Human-to-human transmission; Influenza; Oseltamivir; Peramivir