Antigenic Drift of the Hemagglutinin from an Influenza A (H1N1)pdm09 Clinical Isolate Increases its

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The influenza A (H1N1) pdm09 virus emerged in 2009 and has been continuously circulating in humans for over ten years.Here,we analyzed a clinical influenza A (H1N1) pdm09-infected patient case hospitalized for two months in Guangdong(from December 14,2019 to February 15,2020).This isolate,named A/Guangdong/LCF/2019 (LCF/19),was genetically sequenced,rescued by reverse genetics,and phylogenetically analyzed in the context of other relevant pdm09 isolates.Compared with earlier isolates,this pdm09 virus\' s genetic sequence contains four substitutions,S 186P,T 188I,D 190A,and Q192E,of the hemagglutinin (HA) segment at position 186-192 (H3 numbering) in the epitope Sb,and two of which are located at the 190-helix.Phylogenetic analysis indicated that the epitope Sb started undergoing a rapid antigenic change in 2018.To characterize the pathogenicity of this novel substitution motif,a panel of reassortant viruses containing the LCF/2019 HA segment or the chimeric HA segment with the four substitutions were rescued.Kinetic growth data revealed that the reassortant viruses,including the LCF/2019 with the PTIAAQE substitution,propagated faster than those rescued ones having the STTADQQ motif in the epitope Sb in Madin-Darby Canine Kidney (MDCK) cells.The HI test showed that the binding activity of escape mutant to 2018 pdm09 sera was weaker than GLW/2018,suggesting that old vaccines might not effectively protect people from infection.Due to the difference in the selection of vaccine strains,people vaccinated in the southern hemisphere could still suffer a severe infection if infected with this antigenic drift pdm09 virus.
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