12株H9N2亚型禽流感病毒与Sia-α-2,6-唾液酸受体结合力的变化研究
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摘要
为分析H9N2亚型禽流感病毒(H9N2 AIV)对Sia-α-2,6-唾液酸受体(Sia-α-2,6-Gal)结合力的变化趋势,选择2001~2013年分离自山东省的12株H9N2 AIV进行研究。利用同源建模、分子动力学和分子对接等计算方法,对12株H9N2 AIV的HA蛋白与Sia-α-2,6-Gal之间相互作用进行系统研究,筛选HA蛋白中与Sia-α-2,6-Gal结合的关键氨基酸,并对关键氨基酸进行饱和突变研究。结果显示:随着分离年代临近,H9N2 AIV对Sia-α-2,6-Gal亲和能力有增强趋势,Thr198、Leu234、Met235位点的某种氨基酸突变能够大幅提高HA蛋白与Sia-α-2,6-Gal的结合能力。推测H9N2 AIV对哺乳动物感染能力呈逐渐增强趋。
In order to understand the trend of binding force of Sia-a-2,6-sialic acid receptor(Sia-a-2,6-Gal) on H9 N2 subtype avian influenza virus(H9 N2 AIV),12 strains of H9 N2 AIV isolated from Shandong province during 2001 to 2013 were selected in this study.The interaction between 12 HA proteins of the above H9 N2 AIVs and alpha-2,6-gal was systematically studied with homology modeling,molecular dynamics calculation method,and the molecular docking.And the key amino acids were determined which could affect the change of binding capacity.The key amino acids were studied systematically in saturated mutation research.The result showed that H9 N2 AIV had increased the affinity with alpha-2,6-sialic acid receptors as the isolation time approaching.And it was found that certain mutations in Thr198,Leu234,and Met235 could significantly change the binding capacity of HA protein and disaccharisi-alpha-2,6-gal.It was speculated that H9 N2 AIV had gradually enhanced the ability to infect mammals.
In order to understand the trend of binding force of Sia-a-2,6-sialic acid receptor(Sia-a-2,6-Gal) on H9 N2 subtype avian influenza virus(H9 N2 AIV),12 strains of H9 N2 AIV isolated from Shandong province during 2001 to 2013 were selected in this study.The interaction between 12 HA proteins of the above H9 N2 AIVs and alpha-2,6-gal was systematically studied with homology modeling,molecular dynamics calculation method,and the molecular docking.And the key amino acids were determined which could affect the change of binding capacity.The key amino acids were studied systematically in saturated mutation research.The result showed that H9 N2 AIV had increased the affinity with alpha-2,6-sialic acid receptors as the isolation time approaching.And it was found that certain mutations in Thr198,Leu234,and Met235 could significantly change the binding capacity of HA protein and disaccharisi-alpha-2,6-gal.It was speculated that H9 N2 AIV had gradually enhanced the ability to infect mammals.
引文
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[3]PEIRIS M,YAM W C,CHAN K H,et al.Influenza AH9N2:Aspects of laboratory diagnosis[J].J Clin Microbiol,1999,37(10):3426-3432.
[4]XU C T,FAN W X,WEI R,et al.Isolation and identification of swine influenza recombinant A/Swine/Shandong/1/2003(H9N2)virus[J].Microbes Infect,2004,6(10):919-925.
[5]MATVEEVA V M,KOSHEMETOV Z,MAMADALIEV SM.The development and application of solid-phase ELI-SA for the identification of avian influenza virus and its subtypes H5 and N3 in different biological samples[J].Vestn Ross Akad Med Nauk,2011,3(3):10-14.
[6]BULLOUGH P A,HUGHSON F M,SKEHEL J J,et al.Structure of influenza haemagglutinin at the p H of membrane fusion[J].Nature,1994,371(6492):37-43.
[7]TUMPEY T M,MAINES T R,VAN HOEVEN N,et al.A two-amino acid change in the hemagglutinin of the1918 influenza virus abolishes transmission[J].Science,2007,315(5812):655-659.
[8]PAPPAS C,VISWANATHAN K,CHANDRASEKARANA,et al.Receptor specificity and transmission of H2N2subtype viruses isolated from the pandemic of 1957[J].PLo S One,2010,5(6):e11158.
[9]ROBERTS K L,SHELTON H,SCULL M,et al.Lack of transmission of a human influenza virus with avian receptor specificity between ferrets is not due to decreased virus shedding but rather a lower infectivity in vivo[J].JGen Virol,2011,92(8):1822-1831.
[10]LIU J,STEVENS D J,HAIRE L F,et al.Structures of receptor complexes formed by hemagglutinins from the Asian Influenza pandemic of 1957[J].Proc Natl Acad Sci,2009,106(40):17175-17180.
[11]XU R,MCBRIDE R,PAULSON J C,et al.Structure,receptor binding,and antigenicity of influenza virus hemagglutinins from the 1957 H2N2 pandemic[J].J Virol,2010,84(4):1715-1721.
[12]NIDOM C A,TAKANO R,YAMADA S,et al.Influenza A(H5N1)viruses from pigs,Indonesia[J].Emerg Infect Dis,2010,16(10):1515-1523.
[13]GAMBARYAN A S,MATROSOVICH T Y,PHILIPP J,et al.Receptor-binding profiles of H7 subtype influenza viruses in different host species[J].J Virol,2012,86(8):4370-4378.
[14]SRINIVASAN K,RAMAN R,JAYARAMAN A,et al.Quantitative description of glycan-receptor binding of influenza A virus H7 hemagglutinin[J].PLo S One,2013,8(2):e49597.
[15]YANG H,CARNEY P J,CHANG J C,et al.Structural analysis of the hemagglutinin from the recent 2013 H7N9influenza virus[J].J Virol,2013,87(22):12433-12446.
[16]RAMOS I,KRAMMER F,HAI R,et al.H7N9 influenza viruses interact preferentially with alpha2,3-linked sialic acids and bind weakly to alpha2,6-linked sialic acids[J].J Gen Virol,2013,94(11):2417-2423.
[17]SRINIVASAN K,RAMAN R,JAYARAMAN A,et al.Quantitative description of glycan-receptor binding of influenza A virus H7 hemagglutinin[J].PLo S One,2013,8(2):e49597.
[18]YANG H,CARNEY P J,CHANG J C,et al.Structural analysis of the hemagglutinin from the recent 2013 H7N9influenza virus[J].J Virol,2013,87(22):12433-12446.
[19]BERTRAM S,THIELE S,DREIER C,et al.H7N9 influenza a virus exhibits importin-alpha7-mediated replication in the mammalian respiratory tract[J].Am J Pathol,2017,187(4):831-840.
[20]BUI,C M,GARDNER L,MACINTYRE R,et al.Influenza A H5N1 and H7N9 in China:A spatial risk analysis[J].PLo S One,2017,12(4):e0174980.
[21]LI R,BAI Y,HEANEY A,et al.Inference and forecast of H7N9 influenza in China,2013 to 2015[J].Euro Surveill,2017,16:22(7):e30462.