Genetic tuning of the novel avian influenza A(H7N9) virus during interspecies transmission, China, 2013.
D Wang1
L Yang
R Gao
X Zhang
Y Tan
A Wu
W Zhu
J Zhou
S Zou
Xiyan Li
Y Sun
Y Zhang
Y Liu
T Liu
Y Xiong
J Xu
L Chen
Y Weng
X Qi
J Guo
Xiaodan Li
J Dong
W Huang
Y Zhang
L Dong
X Zhao
L Liu
J Lu
Y Lan
H Wei
L Xin
Y Chen
C Xu
T Chen
Y Zhu
T Jiang
Z Feng
W Yang
Y Wang
H Zhu
Y Guan
G F Gao
D Li
J Han
S Wang
G Wu
Y Shu
Affiliations1 institutions
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing, China.
A novel avian influenza A(H7N9) virus causing human infection emerged in February 2013 in China. To elucidate the mechanism of interspecies transmission, we compared the signature amino acids of avian influenza A(H7N9) viruses from human and non-human hosts and analysed the reassortants of 146 influenza A(H7N9) viruses with full genome sequences. We propose a genetic tuning procedure with continuous amino acid substitutions and reassorting that mediates host adaptation and interspecies transmission. When the early influenza A(H7N9) virus, containing ancestor haemagglutinin (HA) and neuraminidase (NA) genes similar to A/Shanghai/05 virus, circulated in waterfowl and transmitted to terrestrial poultry, it acquired an NA stalk deletion at amino acid positions 69 to 73. Then, receptor binding preference was tuned to increase the affinity to human-like receptors through HA G186V and Q226L mutations in terrestrial poultry. Additional mammalian adaptations such as PB2 E627K were selected in humans. The continual reassortation between H7N9 and H9N2 viruses resulted in multiple genotypes for further host adaptation. When we analysed a potential association of mutations and reassortants with clinical outcome, only the PB2 E627K mutation slightly increased the case fatality rate. Genetic tuning may create opportunities for further adaptation of influenza A(H7N9) and its potential to cause a pandemic.
Amino Acid SubstitutionAnimalsBase SequenceChinaGenome, ViralHumansInfluenza A Virus, H7N9 SubtypeInfluenza in BirdsInfluenza, HumanNeuraminidasePhylogenyPoultryPoultry DiseasesSequence Analysis, DNAViral Proteins
Structured evidence records
Evidence records
6 total
Cross Species Transmission1 records
Cross Species TransmissionExtraction confidence 0.90
Key finding
Avian influenza A(H7N9) transmitted from waterfowl to terrestrial poultry, representing cross-species transmission among non-human avian hosts with associated genetic adaptation.
When the early influenza A(H7N9) virus, containing ancestor haemagglutinin (HA) and neuraminidase (NA) genes similar to A/Shanghai/05 virus, circulated in waterfowl and transmitted to terrestrial poultry, it acquired an NA stalk deletion at amino acid positions 69 to 73.
Method
genome sequencing; phylogenetic analysis
Study design
phylogenetic analysis
Transmission direction
animal-to-animal
Geographic raw
China
Country inferred
China
Genomic Evolution1 records
Genomic EvolutionExtraction confidence 0.85
Key finding
Genomic analysis of avian influenza A(H7N9) viruses revealed specific amino acid substitutions in HA, NA, and PB2 and reassortment with H9N2 viruses that underpin host adaptation and interspecies transmission from birds to humans in China.
We compared the signature amino acids of avian influenza A(H7N9) viruses from human and non-human hosts and analysed the reassortants of 146 influenza A(H7N9) viruses with full genome sequences. When the early influenza A(H7N9) virus, containing ancestor haemagglutinin (HA) and neuraminidase (NA) genes similar to A/Shanghai/05 virus, circulated in waterfowl and transmitted to terrestrial poultry, it acquired an NA stalk deletion at amino acid positions 69 to 73. Then, receptor binding preference was tuned through HA G186V and Q226L mutations in terrestrial poultry, and PB2 E627K was selected in humans.
Receptor binding preference was tuned to increase the affinity to human-like receptors through HA G186V and Q226L mutations in terrestrial poultry. Additional mammalian adaptations such as PB2 E627K were selected in humans.
Genes or proteins
HA; PB2
Receptors
human-like receptors
Mutations
HA G186V; HA Q226L; PB2 E627K
Mechanism types
receptor_binding; mammalian_adaptation
Receptor Usage1 records
Receptor UsageExtraction confidence 0.90
Key finding
Influenza A(H7N9) virus gained HA G186V and Q226L mutations that enhanced binding to human-like receptors, indicating receptor adaptation during transmission from birds to humans.
