甲型流感病毒宿主适应的分子基础及其相关宿主因子的研究进展

doi:10.16288/j.yczz.23-173

遗传 ›› 2023, Vol. 45 ›› Issue (11): 976-985.doi: 10.16288/j.yczz.23-173

甲型流感病毒宿主适应的分子基础及其相关宿主因子的研究进展

孙婷婷(), 岑山(), 王静()

中国医学科学院医药生物技术研究所，北京协和医学院医药生物技术研究所，北京 100050

收稿日期:2023-06-26 修回日期:2023-08-25 出版日期:2023-11-20 发布日期:2023-09-20
通讯作者: 岑山,王静 E-mail:1165852674@qq.com;jingwang@imb.pumc.edu.cn;shancen@imb.pumc.edu.cn
作者简介:孙婷婷，硕士研究生，专业方向：微生物与生化药学。E-mail: 1165852674@qq.com。
基金资助:
国家自然科学基金面上项目(81971950);中国医学科学院医学与健康科技创新工程项目(2021-I2M-1-038)

Progress on viral and host determinants of influenza A virus species specificity

Tingting Sun(), Shan Cen(), Jing Wang()

Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050，China

Received:2023-06-26 Revised:2023-08-25 Published:2023-11-20 Online:2023-09-20
Contact: Shan Cen,Jing Wang E-mail:1165852674@qq.com;jingwang@imb.pumc.edu.cn;shancen@imb.pumc.edu.cn
Supported by:
the National Natural Science Foundation of China(81971950);CAMS Innovation Fund for Medical Sciences(2021-I2M-1-038)

摘要/Abstract

摘要：

甲型流感病毒宿主广泛，传染性强，可引起人畜共患病，严重威胁人类健康和公共卫生安全。甲型流感病毒可以通过基因突变和基因重配等机制不断变异，如果新毒株打破宿主限制获得在人类传播的能力，有可能造成流感大流行。理解流感病毒突破种间屏障的遗传学基础和分子机制，是科学界亟待解决的问题，对有效监控和预防潜在流感大爆发的具有重要的提示作用。本文对目前研究流感病毒宿主适应的分子决定因素展开了综述，着重介绍了病毒本身的遗传变异以及和病毒相互作用的宿主因子的作用，以便为应对下次流感大流行做好理论储备，为抵抗流感寻找新策略。

关键词: 甲型流感病毒, 跨种传播, 宿主适应, 分子基础

Abstract:

Influenza A viruses have a wide range of hosts and are highly infectious, which can cause zoonotic diseases and pose a serious public health threat to human safety. An influenza pandemic could outbreak if new strains gain the ability of human-to-human transmission, either by genetic mutation or by gene reassortment. It is an urgent issue for the scientific community to reveal the genetic basis and molecular mechanisms underlying the interspecies transmission of influenza viruses, which will provide important implications for the effective monitoring and prevention of potential influenza pandemics. In this review, we summarize the molecular determinants of influenza viruses for host adaptation, and highlight the advances in the gene mutations of the virus itself and the interaction between virus and host factors. This will help to make a theoretical reserve for the next influenza pandemic and find new strategies to fight against influenza.

Key words: influenza A virus, interspecies transmission, host adaptation, molecular basis

孙婷婷, 岑山, 王静. 甲型流感病毒宿主适应的分子基础及其相关宿主因子的研究进展[J]. 遗传, 2023, 45(11): 976-985.

Tingting Sun, Shan Cen, Jing Wang. Progress on viral and host determinants of influenza A virus species specificity[J]. Hereditas(Beijing), 2023, 45(11): 976-985.

图/表 3

参考文献 67

[1]	Zhang MM, Liu MB, Bai SM, Zhao C, Li ZJ, Xu JQ, Zhang XY. Influenza A virus-host specificity: an ongoing cross-talk between viral and host factors. Front Microbiol, 2021, 12: 777885. doi: 10.3389/fmicb.2021.777885
[2]	Javanian M, Barary M, Ghebrehewet S, Koppolu V, Vasigala V, Ebrahimpour S. A brief review of influenza virus infection. J Med Virol, 2021, 93(8): 4638-4646. doi: 10.1002/jmv.26990 pmid: 33792930
[3]	Chauhan RP, Gordon ML. An overview of influenza A virus genes, protein functions, and replication cycle highlighting important updates. Virus Genes, 2022, 58(4): 255-269. doi: 10.1007/s11262-022-01904-w
[4]	Long JS, Mistry B, Haslam SM, Barclay WS. Host and viral determinants of influenza A virus species specificity. Nat Rev Microbiol, 2019, 17(2): 67-81. doi: 10.1038/s41579-018-0115-z pmid: 30487536
[5]	Cumulative number of confirmed human cases for avian influenza A(H5N1)reported to WHO, 2003-2023, 31 May 2023. https://www.who.int/publications/m/item/cumulative-number-of-confirmed-human-cases-for-avian-influenza-a (h5n1)-reported-to-who--2003-2023--31-may-2023 (accessed 2023-06-21).
[6]	Samji T. Influenza A: understanding the viral life cycle. Yale J Biol Med, 2009, 82(4): 153-159. pmid: 20027280
[7]	Dong CZ. Advances on genomic evolution of influenza virus. Hereditas(Beijing), 2011, 33(3): 189-197.
	董长征. 流感病毒基因组进化研究进展. 遗传, 2011, 33(3): 189-197.
[8]	Matrosovich M, Tuzikov A, Bovin N, Gambaryan A, Klimov A, Castrucci MR, Donatelli I, Kawaoka Y. Early alterations of the receptor-binding properties of H1, H2, and H3 avian influenza virus hemagglutinins after their introduction into mammals. J Virol, 2000, 74(18): 8502-8512. doi: 10.1128/jvi.74.18.8502-8512.2000 pmid: 10954551
[9]	Shinya K, Ebina M, Yamada S, Ono M, Kasai N, Kawaoka Y. Influenza virus receptors in the human airway. Nature, 2006, 440(7083): 435-436. doi: 10.1038/440435a
[10]	Zhao CK, Pu J. Influence of host sialic acid receptors structure on the host specificity of influenza viruses. Viruses, 2022, 14(10): 2141. doi: 10.3390/v14102141
[11]	Shi Y, Wu Y, Zhang W, Qi JX, Gao GF. Enabling the 'host jump': structural determinants of receptor-binding specificity in influenza A viruses. Nat Rev Microbiol, 2014, 12(12): 822-831. doi: 10.1038/nrmicro3362 pmid: 25383601
[12]	Xu R, de Vries RP, Zhu XY, Nycholat CM, McBride R, Yu WL, Paulson JC, Wilson IA. Preferential recognition of avian-like receptors in human influenza A H7N9 viruses. Science, 2013, 342(6163): 1230-1235. doi: 10.1126/science.1243761 pmid: 24311689
[13]	Stevens J, Blixt O, Chen LM, Donis RO, Paulson JC, Wilson IA. Recent avian H5N1 viruses exhibit increased propensity for acquiring human receptor specificity. J Mol Biol, 2008, 381(5): 1382-1394. doi: 10.1016/j.jmb.2008.04.016 pmid: 18672252
[14]	Kuchipudi SV, Nelli RK, Gontu A, Satyakumar R, Surendran Nair M, Subbiah M. Sialic acid receptors: the key to solving the enigma of zoonotic virus spillover. Viruses, 2021, 13(2): 262. doi: 10.3390/v13020262
[15]	Schrauwen EJA, de Graaf M, Herfst S, Rimmelzwaan GF, Osterhaus ADME, Fouchier RAM. Determinants of virulence of influenza A virus. Eur J Clin Microbiol Infect Dis, 2014, 33(4): 479-490. doi: 10.1007/s10096-013-1984-8
[16]	Li Q, Qi JX, Zhang W, Vavricka CJ, Shi Y, Wei JH, Feng EG, Shen JS, Chen JL, Liu D, He JH, Yan JH, Liu H, Jiang HL, Teng MK, Li XB, Gao GF. The 2009 pandemic H1N1 neuraminidase N1 lacks the 150-cavity in its active site. Nat Struct Mol Biol, 2010, 17(10): 1266-1268. doi: 10.1038/nsmb.1909
[17]	Lakdawala SS, Jayaraman A, Halpin RA, Lamirande EW, Shih AR, Stockwell TB, Lin XD, Simenauer A, Hanson CT, Vogel L, Paskel M, Minai M, Moore I, Orandle M, Das SR, Wentworth DE, Sasisekharan R, Subbarao K. The soft palate is an important site of adaptation for transmissible influenza viruses. Nature, 2015, 526(7571): 122-125. doi: 10.1038/nature15379
[18]	Wang F, Wan ZM, Wang YJ, Wu JS, Fu H, Gao W, Shao HX, Qian K, Ye JQ, Qin AJ. Identification of hemagglutinin mutations caused by neuraminidase antibody pressure. Microbiol Spectr, 2021, 9(3): e0143921. doi: 10.1128/spectrum.01439-21
[19]	Benton DJ, Wharton SA, Martin SR, McCauley JW. Role of neuraminidase in influenza A(H7N9) virus receptor binding. J Virol, 2017, 91(11): e02293-16.
[20]	Nilsson BE te Velthuis AJW, Fodor E,. Role of the PB2 627 domain in influenza A virus polymerase function. J Virol, 2017, 91(7): e02467-16.
[21]	Long JCD, Fodor E. The PB2 subunit of the influenza A virus RNA polymerase is imported into the mitochondrial matrix. J Virol, 2016, 90(19): 8729-8738. doi: 10.1128/JVI.01384-16 pmid: 27440905
[22]	Long JS, Giotis ES, Moncorgé O, Frise R, Mistry B, James J, Morisson M, Iqbal M, Vignal A, Skinner MA, Barclay WS. Species difference in ANP32A underlies influenza A virus polymerase host restriction. Nature, 2016, 529(7584): 101-104. doi: 10.1038/nature16474
[23]	Taubenberger JK, Reid AH, Lourens RM, Wang RX, Jin GZ, Fanning TG. Characterization of the 1918 influenza virus polymerase genes. Nature, 2005, 437(7060): 889-893. doi: 10.1038/nature04230
[24]	de Jong MD, Simmons CP, Thanh TT, Hien VM, Smith GJD, Chau TNB, Hoang DM, Van Vinh Chau N, Khanh TH, Dong VC, Qui PT, Van Cam B, Ha DQ, Guan Y, Peiris JSM, Chinh NT, Hien TT, Farrar J. Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nat Med, 2006, 12(10): 1203-1207. doi: 10.1038/nm1477 pmid: 16964257
[25]	Steel J, Lowen AC, Mubareka S, Palese P. Transmission of influenza virus in a mammalian host is increased by PB2 amino acids 627K or 627E/701N. PLoS Pathog, 2009, 5(1): e1000252. doi: 10.1371/journal.ppat.1000252
[26]	Hayashi T, Wills S, Bussey KA, Takimoto T. Identification of influenza A virus PB2 residues involved in enhanced polymerase activity and virus growth in mammalian cells at low temperatures. J Virol, 2015, 89(15): 8042-8049. doi: 10.1128/JVI.00901-15 pmid: 26018156
[27]	Yamada S, Hatta M, Staker BL, Watanabe S, Imai M, Shinya K, Sakai-Tagawa Y, Ito M, Ozawa M, Watanabe T, Sakabe S, Li CJ, Kim JH, Myler PJ, Phan I, Raymond A, Smith E, Stacy R, Nidom CA, Lank SM, Wiseman RW, Bimber BN, O’Connor DH, Neumann G, Stewart LJ, Kawaoka Y. Biological and structural characterization of a host-adapting amino acid in influenza virus. PLoS Pathog, 2010, 6(8): e1001034. doi: 10.1371/journal.ppat.1001034
[28]	Gabriel G, Klingel K, Otte A, Thiele S, Hudjetz B, Arman-Kalcek G, Sauter M, Shmidt T, Rother F, Baumgarte S, Keiner B, Hartmann E, Bader M, Brownlee GG, Fodor E, Klenk HD. Differential use of importin-α isoforms governs cell tropism and host adaptation of influenza virus. Nat Commun, 2011, 2(1): 156. doi: 10.1038/ncomms1158
[29]	Pumroy RA, Ke S, Hart DJ, Zachariae U, Cingolani G. Molecular determinants for nuclear import of influenza A PB2 by importin α isoforms 3 and 7. Structure, 2015, 23(2): 374-384. doi: 10.1016/j.str.2014.11.015 pmid: 25599645
[30]	Thiele S, Stanelle-Bertram S, Beck S, Kouassi NM, Zickler M, Müller M, Tuku B, Resa-Infante P, van Riel D, Alawi M, Günther T, Rother F, Hügel S, Reimering S, McHardy A, Grundhoff A, Brune W, Osterhaus A, Bader M, Hartmann E, Gabriel G. Cellular importin-Α3 expression dynamics in the lung regulate antiviral response pathways against influenza A virus infection. Cell Rep, 2020, 31(3): 107549. doi: 10.1016/j.celrep.2020.107549
[31]	Domingues P, Hale BG. Functional insights into ANP32A-dependent influenza A virus polymerase host restriction. Cell Rep, 2017, 20(11): 2538-2546. doi: S2211-1247(17)31186-5 pmid: 28903035
[32]	Zhang HL, Zhang ZY, Wang YJ, Wang MY, Wang XF, Zhang X, Ji S, Du C, Chen HL, Wang XJ. Fundamental contribution and host range determination of ANP32A and ANP32B in influenza A virus polymerase activity. J Virol, 2019, 93(13): e00174-19.
[33]	Zhang HL, Li HX, Wang WQ, Wang YJ, Han GZ, Chen HL, Wang XJ. A unique feature of swine ANP32A provides susceptibility to avian influenza virus infection in Pigs. PLoS Pathog, 2020, 16(2): e1008330. doi: 10.1371/journal.ppat.1008330
[34]	Bortz E, Westera L, Maamary J, Steel J, Albrecht RA, Manicassamy B, Chase G, Martínez-Sobrido L, Schwemmle M, García-Sastre A. Host- and strain-specific regulation of influenza virus polymerase activity by interacting cellular proteins. mBio, 2011, 2(4): e00151-11.
[35]	Kawaoka Y, Krauss S, Webster RG.Avian-to-human transmission of the PB1 gene of influenza A viruses in the 1957 and 1968 pandemics. J Virol, 1989, 63(11): 4603-4608. doi: 10.1128/JVI.63.11.4603-4608.1989 pmid: 2795713
[36]	Lin RW, Chen GW, Sung HH, Lin RJ, Yen LC, Tseng YL, Chang YK, Lien SP, Shih SR, Liao CL. Naturally occurring mutations in PB1 affect influenza A virus replication fidelity, virulence, and adaptability. J Biomed Sci, 2019, 26(1): 55. doi: 10.1186/s12929-019-0547-4
[37]	Zhang XH, Li YG, Jin S, Zhang YM, Sun LY, Hu XY, Zhao ML, Li FX, Wang TC, Sun WY, Feng N, Wang HM, He HB, Zhao YK, Yang ST, Xia XZ, Gao YW. PB1 S524G mutation of wild bird-origin H3N8 influenza A virus enhances virulence and fitness for transmission in mammals. Emerg Microbes Infect, 2021, 10(1): 1038-1051. doi: 10.1080/22221751.2021.1912644
[38]	Yoshizumi T, Ichinohe T, Sasaki O, Otera H, Kawabata SI, Mihara K, Koshiba T. Influenza A virus protein PB1-F2 translocates into mitochondria via Tom40 channels and impairs innate immunity. Nat Commun, 2014, 5(1): 4713. doi: 10.1038/ncomms5713
[39]	Hara K, Schmidt FI, Crow M, Brownlee GG. Amino acid residues in the N-terminal region of the PA subunit of influenza A virus RNA polymerase play a critical role in protein stability, endonuclease activity, cap binding, and virion RNA promoter binding. J Virol, 2006, 80(16), 7789-7798. doi: 10.1128/JVI.00600-06 pmid: 16873236
[40]	Song MS, Pascua PNQ, Lee JH, Baek YH, Lee OJ, Kim CJ, Kim H, Webby RJ, Webster RG, Choi YK. The polymerase acidic protein gene of influenza A virus contributes to pathogenicity in a mouse model. J Virol, 2009, 83(23): 12325-12335. doi: 10.1128/JVI.01373-09
[41]	Gabriel G, Dauber B, Wolff T, Planz O, Klenk HD, Stech J. The viral polymerase mediates adaptation of an avian influenza virus to a mammalian host. Proc Natl Acad Sci USA, 2005, 102(51): 18590-18595. doi: 10.1073/pnas.0507415102 pmid: 16339318
[42]	Jagger BW, Wise HM, Kash JC, Walters KA, Wills NM, Xiao YL, Dunfee RL, Schwartzman LM, Ozinsky A, Bell GL, Dalton RM, Lo A, Efstathiou S, Atkins JF, Firth AE, Taubenberger JK, Digard P. An overlapping protein- coding region in influenza A virus segment 3 modulates the host response. Science, 2012, 337(6091): 199-204. doi: 10.1126/science.1222213 pmid: 22745253
[43]	Garten RJ, Davis CT, Russell CA, Shu B, Lindstrom S, Balish A, Sessions WM, Xu XY, Skepner E, Deyde V, Okomo-Adhiambo M, Gubareva L, Barnes J, Smith CB, Emery SL, Hillman MJ, Rivailler P, Smagala J, de Graaf M, Burke DF, Fouchier RAM, Pappas C, Alpuche-Aranda CM, López-Gatell H, Olivera H, López I, Myers CA, Faix D, Blair PJ, Yu C, Keene KM, Dotson PD, Boxrud D, Sambol AR, Abid SH, St George K, Bannerman T, Moore AL, Stringer DJ, Blevins P, Demmler-Harrison GJ, Ginsberg M, Kriner P, Waterman S, Smole S, Guevara HF, Belongia EA, Clark PA, Beatrice ST, Donis R, Katz J, Finelli L, Bridges CB, Shaw M, Jernigan DB, Uyeki TM, Smith DJ, Klimov AI, Cox NJ. Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science, 2009, 325(5937): 197-201.
[44]	Sun YP, Hu Z, Zhang XX, Chen MY, Wang Z, Xu GL, Bi YH, Tong Q, Wang MY, Sun HL, Pu J, Iqbal M, Liu JH. An R195K mutation in the PA-X protein increases the virulence and transmission of influenza A virus in mammalian hosts. J Virol, 2020, 94(11): e01817-e01819.
[45]	Kukol A, Hughes DJ. Large-scale analysis of influenza A virus nucleoprotein sequence conservation reveals potential drug-target sites. Virology, 2014, 454-455: 40-47.
[46]	Gabriel G, Herwig A, Klenk HD. Interaction of polymerase subunit PB2 and NP with importin α1 is a determinant of host range of influenza A virus. PLoS Pathog, 2008, 4(2): e11. doi: 10.1371/journal.ppat.0040011
[47]	Zimmermann P, Mänz B, Haller O, Schwemmle M, Kochs G. The viral nucleoprotein determines Mx sensitivity of influenza A viruses. J Virol, 2011, 85(16): 8133-8140. doi: 10.1128/JVI.00712-11 pmid: 21680506
[48]	Peukes J, Xiong XL, Erlendsson S, Qu K, Wan W, Calder LJ, Schraidt O, Kummer S, Freund SMV, Kräusslich HG, Briggs JAG. The native structure of the assembled matrix protein 1 of influenza A virus. Nature, 2020, 587(7834): 495-498. doi: 10.1038/s41586-020-2696-8
[49]	Kordyukova LV, Shtykova EV, Baratova LA, Svergun DI, Batishchev OV. Matrix proteins of enveloped viruses: A case study of influenza A virus M1 protein. J Biomol Struct Dyn, 2019, 37(3): 671-690. doi: 10.1080/07391102.2018.1436089 pmid: 29388479
[50]	Calder LJ, Rosenthal PB. Cryomicroscopy provides structural snapshots of influenza virus membrane fusion. Nat Struct Mol Biol, 2016, 23(9): 853-858. doi: 10.1038/nsmb.3271 pmid: 27501535
[51]	Ito T, Gorman OT, Kawaoka Y, Bean WJ, Webster RG.Evolutionary analysis of the influenza A virus M gene with comparison of the M1 and M2 proteins. 1991, 65(10): 5491-5498.
[52]	Li FT, Liu JY, Yang JZ, Sun HR, Jiang ZM, Wang CX, Zhang X, Yu YH, Zhao CK, Pu J, Sun YP, Chang KC, Liu JH, Sun HL. H9N2 virus-derived M1 protein promotes H5N6 virus release in mammalian cells: Mechanism of avian influenza virus inter-species infection in humans. PLoS Pathog, 2021, 17(12): e1010098. doi: 10.1371/journal.ppat.1010098
[53]	Zheng HB, Ma LP, Gui R, Lin X, Ke XL, Jian XQ, Ye C, Chen QJ.G protein subunit Β1 facilitates influenza A virus replication by promoting the nuclear import of PB2. J Virol, 2022, 96(12): e0049422. doi: 10.1128/jvi.00494-22
[54]	Rosário-Ferreira N, Preto AJ, Melo R, Moreira IS, Brito RMM. The central role of non-structural protein 1 (NS1) in influenza biology and infection. Int J Mol Sci, 2020, 21(4): 1511. doi: 10.3390/ijms21041511
[55]	Kim HJ, Jeong MS, Jang SB. Structure and activities of the NS1 influenza protein and progress in the development of small-molecule drugs. Int J Mol Sci, 2021, 22(8): 4242. doi: 10.3390/ijms22084242
[56]	Brunotte L, Flies J, Bolte H, Reuther P, Vreede F, Schwemmle M. The nuclear export protein of H5N1 influenza A viruses recruits Matrix 1 (M1) protein to the viral ribonucleoprotein to mediate nuclear export. J Biol Chem, 2014, 289(29): 20067-20077. doi: 10.1074/jbc.M114.569178 pmid: 24891509
[57]	Reuther P, Giese S, Götz V, Kilb N, Mänz B, Brunotte L, Schwemmle M. Adaptive mutations in the nuclear export protein of human-derived H5N1 strains facilitate a polymerase activity-enhancing conformation. J Virol, 2014, 88(1): 263-271. doi: 10.1128/JVI.01495-13 pmid: 24155389
[58]	Selman M, Dankar SK, Forbes NE, Jia JJ, Brown EG. Adaptive mutation in influenza A virus non-structural gene is linked to host switching and induces a novel protein by alternative splicing. Emerg Microbes Infect, 2012, 1(11): e42.
[59]	Vasin AV, Temkina OA, Egorov VV, Klotchenko SA, Plotnikova MA, Kiselev OI. Molecular mechanisms enhancing the proteome of influenza A viruses: an overview of recently discovered proteins. Virus Res, 2014, 185: 53-63. doi: 10.1016/j.virusres.2014.03.015 pmid: 24675275
[60]	Chung YT, Kuan CY, Liao GR, Albrecht RA, Tseng YY, Hsu YC, Ou SC, Hsu WL. A variant NS1 protein from H5N2 avian influenza virus suppresses PKR activation and promotes replication and virulence in mammals. Emerg Microbes Infect, 2022, 11(1): 2291-2303. doi: 10.1080/22221751.2022.2114853
[61]	Rouzine IM, Rozhnova G. Antigenic evolution of viruses in host populations. PLoS Pathog, 2018, 14(9): e1007291. doi: 10.1371/journal.ppat.1007291
[62]	Łuksza M, Lässig M. A predictive fitness model for influenza. Nature, 2014, 507(7490): 57-61. doi: 10.1038/nature13087
[63]	Yin R, Zhang Y, Zhou XR, Kwoh CK. Time Series Computational Prediction of Vaccines for Influenza A H3N2 with Recurrent Neural Networks. J Bioinform Comput Biol, 2020, 18(1): 2040002. doi: 10.1142/S0219720020400028
[64]	Burton TD, Eyre NS. Applications of deep mutational scanning in virology. Viruses, 2021, 13(6): 1020. doi: 10.3390/v13061020
[65]	Moncla LH, Florek KR, Friedrich TC. Influenza evolution: new insights into an old foe. Trends Microbiol, 2017, 25(6): 432-434. doi: S0966-842X(17)30091-4 pmid: 28478941
[66]	Starr TN, Greaney AJ, Hilton SK, Ellis D, Crawford KHD, Dingens AS, Navarro MJ, Bowen JE, Tortorici MA, Walls AC, King NP, Veesler D, Bloom JD. Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding. Cell, 2020, 182(5): 1295-1310.e20. doi: S0092-8674(20)31003-5 pmid: 32841599
[67]	Xia S, Liu ZZ, Jiang SB. High-throughput screening of mutations affecting SARS-CoV-2 spike functions. Trends Immunol, 2023, 44(5): 321-323. doi: 10.1016/j.it.2023.03.010 pmid: 37031063

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病毒蛋白	相关宿主因子	主要功能
PB2	Importin-α	禽类病毒复制依赖importin-α3，而人类病毒依赖importin-α7
	ANP32A	禽类ANP32A具有独特的33个氨基酸序列，支持禽类流感病毒聚合酶活性
	DDX17	人的DDX17同源物促进了人适应性流感病毒的复制
NP	MxA	NP适应性突变可使病毒逃避MxA的限制
M	GNB1	促进M1和HA相互作用，调节病毒复制

甲型流感病毒宿主适应的分子基础及其相关宿主因子的研究进展

Progress on viral and host determinants of influenza A virus species specificity

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变异蛋白	氨基酸位点	禽类	人类
HA(H1)	190	E	D
	225	G	D
	138	A	S
HA(H2,H3)	226	Q	L
HA(H2,H3)	228	G	S
HA(H5,H7)	221	T	P
HA(H5,H7)	186	G	V
PB2	627	E	K
	701	D	N
	271	T	A
	590	G	S
	591	Q	R
PB1	216	S	G
PB1	524	S	G
PA	522	T	S
	349	E	G
	97	T	I
PA-X	195	R	K
NP	319	D	K
NS1	92	D	E
NS1	42	P	S
NS2	16	M	I
	41	Y	C
	75	E	G
NS3	374	A	G
NS3	125	D	G