Structure and receptor binding preferences of recombinant hemagglutinins from avian and human H6 and H10 influenza A virus subtypes

Journal of Virology

Volumn 89, Issue 8, 2015, Pages 4612-4623

  Yang, Hua ^a   Carney, Paul J ^a   Chang, Jessie C ^a   Villanueva, Julie M ^a   Stevens, James ^a  

^a NATIONAL CENTER FOR IMMUNIZATION AND RESPIRATORY DISEASES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GLYCAN; INFLUENZA VIRUS HEMAGGLUTININ; HEMAGGLUTININ, AVIAN INFLUENZA A VIRUS; HEMAGGLUTININ, HUMAN INFLUENZA A VIRUS; PROTEIN BINDING; RECOMBINANT PROTEIN;

ARTICLE; AVIAN INFLUENZA VIRUS; INFLUENZA VIRUS A; INFLUENZA VIRUS A H10N8; INFLUENZA VIRUS A H6N1; INFLUENZA VIRUS A H7N9; MICROARRAY ANALYSIS; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN PURIFICATION; PROTEIN STRUCTURE; RECEPTOR BINDING; VIRUS TYPING; VIRUS VIRULENCE; ANIMAL; BIRD; CHEMICAL STRUCTURE; CHEMISTRY; CRYSTALLIZATION; GENETICS; HUMAN; INFLUENZA A VIRUS (H10N8); METABOLISM; MOLECULAR CLONING; PROTEIN CONFORMATION; SPECIES DIFFERENCE;

AVES; INFLUENZA A VIRUS;

ANIMALS; BIRDS; CLONING, MOLECULAR; CRYSTALLIZATION; HEMAGGLUTININ GLYCOPROTEINS, INFLUENZA VIRUS; HUMANS; INFLUENZA A VIRUS, H10N8 SUBTYPE; MICROARRAY ANALYSIS; MODELS, MOLECULAR; PROTEIN BINDING; PROTEIN CONFORMATION; RECOMBINANT PROTEINS; SPECIES SPECIFICITY;

EID: 84925438637     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.03456-14     Document Type: Article

References (71)

1. Fouchier RA, Munster V, Wallensten A, Bestebroer TM, Herfst S, Smith D, Rimmelzwaan GF, Olsen B, Osterhaus AD. 2005. Characterization of a novel influenzaAvirus hemagglutinin subtype (H16) obtained from black-headed gulls. J Virol 79:2814-2822. http://dx.doi.org/10.1128/JVI.79.5.2814-2822.2005.
2. Tong S, Li Y, Rivailler P, Conrardy C, Castillo DA, Chen LM, Recuenco S, Ellison JA, Davis CT, York IA, Turmelle AS, Moran D, Rogers S, Shi M, Tao Y, Weil MR, Tang K, Rowe LA, Sammons S, Xu X, Frace M, Lindblade KA, Cox NJ, Anderson LJ, Rupprecht CE, Donis RO. 2012. A distinct lineage of influenza A virus from bats. Proc Natl Acad Sci U S A 109:4269-4274. http://dx.doi.org/10.1073/pnas.1116200109.
3. Tong S, Zhu X, Li Y, Shi M, Zhang J, Bourgeois M, Yang H, Chen X, Recuenco S, Gomez J, Chen LM, Johnson A, Tao Y, Dreyfus C, Yu W, McBride R, Carney PJ, Gilbert AT, Chang J, Guo Z, Davis CT, Paulson JC, Stevens J, Rupprecht CE, Holmes EC, Wilson IA, Donis RO. 2013. New World bats harbor diverse influenza A viruses. PLoS Pathog 9:e1003657. http://dx.doi.org/10.1371/journal.ppat.1003657.
4. Thompson MG, Shay DK, Zhou H, Bridges CB, Cheng PY, Burns E, Bresee JS, Cox NJ. 2010. Estimates of deaths associated with seasonal influenza-United States, 1976-2007. MMWR Morb Mortal Wkly Rep 59:1057-1062.
5. Bean WJ, Schell M, Katz J, Kawaoka Y, Naeve C, Gorman O, Webster RG. 1992. Evolution of the H3 influenza virus hemagglutinin from human and nonhuman hosts. J Virol 66:1129-1138.
6. Garten RJ, Davis CT, Russell CA, Shu B, Lindstrom S, Balish A, Sessions WM, Xu X, 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 RA, Pappas C, Alpuche-Aranda CM, Lopez-Gatell H, Olivera H, Lopez I, Myers CA, Faix D, Blair PJ, Yu C, Keene KM, Dotson PD, Jr, 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. 2009. Antigenic and genetic characteristics of swineorigin 2009 A(H1N1) influenza viruses circulating in humans. Science 325:197-201. http://dx.doi.org/10.1126/science.1176225.
7. Reid AH, Taubenberger JK. 2003. The origin of the 1918 pandemic influenza virus: a continuing enigma. J Gen Virol 84:2285-2292. http://dx.doi.org/10.1099/vir.0.19302-0.
8. Scholtissek C, Rohde W, Von Hoyningen V, Rott R. 1978. On the origin of the human influenza virus subtypes H2N2 and H3N2. Virology 87:13-20. http://dx.doi.org/10.1016/0042-6822(78)90153-8.
9. de Jong JC, Claas EC, Osterhaus AD, Webster RG, Lim WL. 1997. A pandemic warning? Nature 389:554. http://dx.doi.org/10.1038/39218.
10. Zhuang P, Wei L. 2014. Sichuan man dies in first human case of H5N6 bird flu. http://www.scmp.com/news/china/article/1506142/sichuan-poultry-farmer-confirmed-dead-new-bird-flu-strain-h5n6. Accessed 22 January 2015.
11. Centers for Disease Control and Prevention. 2004. Update: influenza activity-United States and worldwide, 2003-04 season, and composition of the 2004-05 influenza vaccine. MMWR Morb Mortal Wkly Rep 53:547-552.
12. Hirst M, Astell CR, Griffith M, Coughlin SM, Moksa M, Zeng T, Smailus DE, Holt RA, Jones S, Marra MA, Petric M, Krajden M, Lawrence D, Mak A, Chow R, Skowronski DM, Tweed SA, Goh S, Brunham RC, Robinson J, Bowes V, Sojonky K, Byrne SK, Li Y, Kobasa D, Booth T, Paetzel M. 2004. Novel avian influenza H7N3 strain outbreak, British Columbia Emerg Infect Dis 10:2192-2195. http://dx.doi.org/10.3201/eid1012.040743.
13. Fouchier RA, Schneeberger PM, Rozendaal FW, Broekman JM, Kemink SA, Munster V, Kuiken T, Rimmelzwaan GF, Schutten M, Van Doornum GJ, Koch G, Bosman A, Koopmans M, Osterhaus AD. 2004. Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome. Proc Natl Acad Sci U S A 101:1356-1361. http://dx.doi.org/10.1073/pnas.0308352100.
14. Peiris M, Yuen KY, Leung CW, Chan KH, Ip PL, Lai RW, Orr WK, Shortridge KF. 1999. Human infection with influenza H9N2. Lancet 354: 916-917. http://dx.doi.org/10.1016/S0140-6736(99)03311-5.
15. WHO. 2013. Avian influenza A(H7N9). World Health Organization, Geneva, Switzerland.
16. Bi Y, Xie Q, Zhang S, Li Y, Xiao H, Jin T, Zheng W, Li J, Jia X, Sun L, Liu J, Qin C, Gao GF, Liu W. 2015. Assessment of the internal genes of influenza A (H7N9) virus contributing to the high pathogenicity in mice. J Virol 89:2-13. http://dx.doi.org/10.1128/JVI.02390-14.
17. Yuan J, Zhang L, Kan X, Jiang L, Yang J, Guo Z, Ren Q. 2013. Origin and molecular characteristics of a novel 2013 avian influenza A(H6N1) virus causing human infection in Taiwan. Clin Infect Dis 57:1367-1368. http://dx.doi.org/10.1093/cid/cit479.
18. Lee MS, Chang PC, Shien JH, Cheng MC, Chen CL, Shieh HK. 2006. Genetic and pathogenic characterization of H6N1 avian influenza viruses isolated in Taiwan between 1972 and 2005. Avian Dis 50:561-571. http://dx.doi.org/10.1637/7640-050106R.1.
19. Senne DA. 2003. Avian influenza in the Western Hemisphere including the Pacific Islands and Australia. Avian Dis 47:798-805. http://dx.doi.org/10.1637/0005-2086-47.s3.798.
20. Myers KP, Setterquist SF, Capuano AW, Gray GC. 2007. Infection due to 3 avian influenza subtypes in United States veterinarians. Clin Infect Dis 45:4-9. http://dx.doi.org/10.1086/518579.
21. Shortridge KF. 1992. Pandemic influenza: a zoonosis? Semin Respir Infect 7:11-25.
22. Shi W, Shi Y, Wu Y, Liu D, Gao GF. 2013. Origin and molecular characterization of the human-infecting H6N1 influenza virus in Taiwan. Protein Cell 4:846-853. http://dx.doi.org/10.1007/s13238-013-3083-0.
23. Wang G, Deng G, Shi J, Luo W, Zhang G, Zhang Q, Liu L, Jiang Y, Li C, Sriwilaijaroen N, Hiramatsu H, Suzuki Y, Kawaoka Y, Chen H. 2014. H6 influenza viruses pose a potential threat to human health. J Virol 88: 3953-3964. http://dx.doi.org/10.1128/JVI.03292-13.
24. Imai M, Watanabe T, Hatta M, Das SC, Ozawa M, Shinya K, Zhong G, Hanson A, Katsura H, Watanabe S, Li C, Kawakami E, Yamada S, Kiso M, Suzuki Y, Maher EA, Neumann G, Kawaoka Y. 2012. Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature 486:420-428.
25. Chen H, Yuan H, Gao R, Zhang J, Wang D, Xiong Y, Fan G, Yang F, Li X, Zhou J, Zou S, Yang L, Chen T, Dong L, Bo H, Zhao X, Zhang Y, Lan Y, Bai T, Dong J, Li Q, Wang S, Zhang Y, Li H, Gong T, Shi Y, Ni X, Li J, Zhou J, Fan J, Wu J, Zhou X, Hu M, Wan J, Yang W, Li D, Wu G, Feng Z, Gao GF, Wang Y, Jin Q, Liu M, Shu Y. 2014. Clinical and epidemiological characteristics of a fatal case of avian influenza A H10N8 virus infection: a descriptive study. Lancet 383:714-721. http://dx.doi.org/10.1016/S0140-6736(14)60111-2.
26. Garcia-Sastre A, Schmolke M. 2014. Avian influenza A H10N8-a virus on the verge? Lancet 383:676-677. http://dx.doi.org/10.1016/S0140-6736(14)60163-X.
27. Parry J. 2014. H10N8 avian flu virus claims its first known human casualty. BMJ 348:g1360. http://dx.doi.org/10.1136/bmj.g1360.
28. Ni X, He F, Hu M, Zhou X, Wang B, Feng C, Wu Y, Li Y, Tu J, Li H, Liu M, Chen H, Chen S. 2015. Investigation of avian influenza virus in poultry and wild birds due to novel avian-origin influenza A(H10N8) in Nanchang City, China. Microbes Infect 17:48-53. http://dx.doi.org/10.1016/j.micinf.2014.09.007.
29. Arzey GG, Kirkland PD, Arzey KE, Frost M, Maywood P, Conaty S, Hurt AC, Deng YM, Iannello P, Barr I, Dwyer DE, Ratnamohan M, McPhie K, Selleck P. 2012. Influenza virus A (H10N7) in chickens and poultry abattoir workers, Australia. Emerg Infect Dis 18:814-816. http://dx.doi.org/10.3201/eid1805.111852.
30. Pan American Health Organization. 2004. Avian influenza virus A (H10N7) circulating among humans in Egypt. PAHO Weekly EID Updates. http://www.paho.org/hq/index.php?option=com=docman&task=doc_details&gid=8363&Itemid=270&lang=en.
31. Gao R, Cao B, Hu Y, Feng Z, Wang D, Hu W, Chen J, Jie Z, Qiu H, Xu K, Xu X, Lu H, Zhu W, Gao Z, Xiang N, Shen Y, He Z, Gu Y, Zhang Z, Yang Y, Zhao X, Zhou L, Li X, Zou S, Zhang Y, Li X, Yang L, Guo J, Dong J, Li Q, Dong L, Zhu Y, Bai T, Wang S, Hao P, Yang W, Zhang Y, Han J, Yu H, Li D, Gao GF, Wu G, Wang Y, Yuan Z, Shu Y. 2013. Human infection with a novel avian-origin influenza A (H7N9) virus. N Engl J Med 368:1888-1897. http://dx.doi.org/10.1056/NEJMoa1304459.
32. Guan Y, Shortridge KF, Krauss S, Webster RG. 1999. Molecular characterization of H9N2 influenza viruses: were they the donors of the "internal" genes of H5N1 viruses in Hong Kong? Proc Natl Acad Sci U S A 96:9363-9367. http://dx.doi.org/10.1073/pnas.96.16.9363.
33. Wei SH, Yang JR, Wu HS, Chang MC, Lin JS, Lin CY, Liu YL, Lo YC, Yang CH, Chuang JH, Lin MC, Chung WC, Liao CH, Lee MS, Huang WT, Chen PJ, Liu MT, Chang FY. 2013. Human infection with avian influenza A H6N1 virus: an epidemiological analysis. Lancet Respir Med 1:771-778. http://dx.doi.org/10.1016/S2213-2600(13)70221-2.
34. Matrosovich MN, Gambaryan AS, Teneberg S, Piskarev VE, Yamnikova SS, Lvov DK, Robertson JS, Karlsson KA. 1997. Avian influenza A viruses differ from human viruses by recognition of sialyloligosaccharides and gangliosides and by a higher conservation of theHAreceptor-binding site. Virology 233:224-234. http://dx.doi.org/10.1006/viro.1997.8580.
35. Rogers GN, Paulson JC, Daniels RS, Skehel JJ, Wilson IA, Wiley DC. 1983. Single amino acid substitutions in influenza haemagglutinin change receptor binding specificity. Nature 304:76-78. http://dx.doi.org/10.1038/304076a0.
36. Belser JA, Gustin KM, Pearce MB, Maines TR, Zeng H, Pappas C, Sun X, Carney PJ, Villanueva JM, Stevens J, Katz JM, Tumpey TM. 2013. Pathogenesis and transmission of avian influenza A (H7N9) virus in ferrets and mice. Nature 501:556-559. http://dx.doi.org/10.1038/nature12391.
37. Frank S, Kammerer RA, Mechling D, Schulthess T, Landwehr R, Bann J, Guo Y, Lustig A, Bachinger HP, Engel J. 2001. Stabilization of short collagen-like triple helices by protein engineering. J Mol Biol 308:1081-1089. http://dx.doi.org/10.1006/jmbi.2001.4644.
38. Yang H, Carney PJ, Chang JC, Villanueva JM, Stevens J. 2013. Structural analysis of the hemagglutinin from the recent 2013 H7N9 influenza virus. J Virol 87:12433-12446. http://dx.doi.org/10.1128/JVI.01854-13.
39. Yang H, Carney P, Stevens J. 2010. Structure and receptor binding properties of a pandemic H1N1 virus hemagglutinin. PLoS Curr 2010: RRN1152. http://dx.doi.org/10.1371/currents.RRN1152.
40. Yang H, Carney PJ, Donis RO, Stevens J. 2012. Structure and receptor complexes of the hemagglutinin from a highly pathogenic H7N7 influenza virus. J Virol 86:8645-8652. http://dx.doi.org/10.1128/JVI.00281-12.
41. Yang H, Chen LM, Carney PJ, Donis RO, Stevens J. 2010. Structures of receptor complexes of a North American H7N2 influenza hemagglutinin with a loop deletion in the receptor binding site. PLoS Pathog 6:e1001081. http://dx.doi.org/10.1371/journal.ppat.1001081.
42. Chayen NE, Shaw-Steward PD, Blow DM. 1992. Microbatch crystallization under oil-a new technique allowing many small volume crystallization experiments J Cryst Growth 122:176-180.
43. Otwinowski Z, Minor W. 1997. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol 276:307-326.
44. McCoy AJ, Grosse-Kunstleve RW, Storoni LC, Read RJ. 2005. Likelihood-enhanced fast translation functions. Acta Crystallogr D Biol Crystallogr 61:458-464. http://dx.doi.org/10.1107/S0907444905001617.
45. Emsley P, Cowtan K. 2004. Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr 60:2126-2132. http://dx.doi.org/10.1107/S0907444904019158.
46. Adams PD, Afonine PV, Bunkoczi G, Chen VB, Davis IW, Echols N, Headd JJ, Hung LW, Kapral GJ, Grosse-Kunstleve RW, McCoy AJ, Moriarty NW, Oeffner R, Read RJ, Richardson DC, Richardson JS, Terwilliger TC, Zwart PH. 2010. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr 66: 213-221. http://dx.doi.org/10.1107/S0907444909052925.
47. Winn MD, Isupov MN, Murshudov GN. 2001. Use of TLS parameters to model anisotropic displacements in macromolecular refinement. Acta Crystallogr D Biol Crystallogr 57:122-133. http://dx.doi.org/10.1107/S0907444900014736.
48. Davis IW, Leaver-Fay A, Chen VB, Block JN, Kapral GJ, Wang X, Murray LW, Arendall WB, III, Snoeyink J, Richardson JS, Richardson DC. 2007. MolProbity: all-atom contacts and structure validation for proteins and Nucleic acids. Nucleic Acids Res 35:W375-W383. http://dx.doi.org/10.1093/nar/gkm216.
49. Ha Y, Stevens DJ, Skehel JJ, Wiley DC. 2001. X-ray structures of H5 avian and H9 swine influenza virus hemagglutinins bound to avian and human receptor analogs. Proc Natl Acad Sci U S A 98:11181-11186. http://dx.doi.org/10.1073/pnas.201401198.
50. Ha Y, Stevens DJ, Skehel JJ, Wiley DC. 2003. X-ray structure of the hemagglutinin of a potential H3 avian progenitor of the 1968 Hong Kong pandemic influenza virus. Virology 309:209-218. http://dx.doi.org/10.1016/S0042-6822(03)00068-0.
51. Liu J, Stevens DJ, Haire LF, Walker PA, Coombs PJ, Russell RJ, Gamblin SJ, Skehel JJ. 2009. Structures of receptor complexes formed by hemagglutinins from the Asian influenza pandemic of 1957. Proc Natl Acad Sci U S A 106:17175-17180. http://dx.doi.org/10.1073/pnas.0906849106.
52. Russell RJ, Gamblin SJ, Haire LF, Stevens DJ, Xiao B, Ha Y, Skehel JJ. 2004. H1 and H7 influenza haemagglutinin structures extend a structural classification of haemagglutinin subtypes. Virology 325:287-296. http://dx.doi.org/10.1016/j.virol.2004.04.040.
53. Russell RJ, Kerry PS, Stevens DJ, Steinhauer DA, Martin SR, Gamblin SJ, Skehel JJ. 2008. Structure of influenza hemagglutinin in complex with an inhibitor of membrane fusion. Proc Natl Acad Sci U S A 105:17736-17741. http://dx.doi.org/10.1073/pnas.0807142105.
54. Stevens J, Blixt O, Tumpey TM, Taubenberger JK, Paulson JC, Wilson IA. 2006. Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus. Science 312:404-410. http://dx.doi.org/10.1126/science.1124513.
55. Stevens J, Corper AL, Basler CF, Taubenberger JK, Palese P, Wilson IA. 2004. Structure of the uncleaved human H1 hemagglutinin from the extinct 1918 influenza virus. Science 303:1866-1870. http://dx.doi.org/10.1126/science.1093373.
56. Wilson IA, Skehel JJ, Wiley DC. 1981. Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 A resolution. Nature 289: 366-373. http://dx.doi.org/10.1038/289366a0.
57. Vachieri SG, Xiong X, Collins PJ, Walker PA, Martin SR, Haire LF, Zhang Y, McCauley JW, Gamblin SJ, Skehel JJ. 2014. Receptor binding by H10 influenza viruses. Nature 511:475-477. http://dx.doi.org/10.1038/nature13443.
58. Yang H, Chang JC, Guo Z, Carney PJ, Shore DA, Donis RO, Cox NJ, Villanueva JM, Klimov AI, Stevens J. 2014. Structural stability of influenza A(H1N1)pdm09 virus hemagglutinins. J Virol 88:4828-4838. http://dx.doi.org/10.1128/JVI.02278-13.
59. Lin YP, Xiong X, Wharton SA, Martin SR, Coombs PJ, Vachieri SG, Christodoulou E, Walker PA, Liu J, Skehel JJ, Gamblin SJ, Hay AJ, Daniels RS, McCauley JW. 2012. Evolution of the receptor binding properties of the influenza A(H3N2) hemagglutinin. Proc Natl Acad Sci U S A 109:21474-21479. http://dx.doi.org/10.1073/pnas.1218841110.
60. Wu Y, Wu Y, Tefsen B, Shi Y, Gao GF. 2014. Bat-derived influenza-like viruses H17N10 and H18N11. Trends Microbiol 22:183-191. http://dx.doi.org/10.1016/j.tim.2014.01.010.
61. Neumann G, Kawaoka Y. 2006. Host range restriction and pathogenicity in the context of influenza pandemic. Emerg Infect Dis 12:881-886. http://dx.doi.org/10.3201/eid1206.051336.
62. Matrosovich M, Tuzikov A, Bovin N, Gambaryan A, Klimov A, Castrucci MR, Donatelli I, Kawaoka Y. 2000. Early alterations of the receptor-binding properties of H1, H2, and H3 avian influenza virus hemagglutinins after their introduction into mammals. J Virol 74:8502-8512. http://dx.doi.org/10.1128/JVI.74.18.8502-8512.2000.
63. Nobusawa E, Ishihara H, Morishita T, Sato K, Nakajima K. 2000. Change in receptor-binding specificity of recent human influenza A viruses (H3N2): a single amino acid change in hemagglutinin altered its recognition of sialyloligosaccharides. Virology 278:587-596. http://dx.doi.org/10.1006/viro.2000.0679.
64. Stevens J, Blixt O, Chen LM, Donis RO, Paulson JC, Wilson IA. 2008. Recent avian H5N1 viruses exhibit increased propensity for acquiring human receptor specificity. J Mol Biol 381:1382-1394. http://dx.doi.org/10.1016/j.jmb.2008.04.016.
65. Xiong X, Martin SR, Haire LF, Wharton SA, Daniels RS, Bennett MS, McCauley JW, Collins PJ, Walker PA, Skehel JJ, Gamblin SJ. 2013. Receptor binding by an H7N9 influenza virus from humans. Nature 499: 496-499. http://dx.doi.org/10.1038/nature12372.
66. Daniels RS, Douglas AR, Skehel JJ, Wiley DC. 1983. Analyses of the antigenicity of influenza haemagglutinin at the pH optimum for virusmediated membrane fusion. J Gen Virol 64:1657-1662. http://dx.doi.org/10.1099/0022-1317-64-8-1657.
67. Popova L, Smith K, West AH, Wilson PC, James JA, Thompson LF, Air GM. 2012. Immunodominance of antigenic site B over site A of hemagglutinin of recent H3N2 influenza viruses. PLoS One 7:e41895. http://dx.doi.org/10.1371/journal.pone.0041895.
68. Stray SJ, Pittman LB. 2012. Subtype-and antigenic site-specific differences in biophysical influences on evolution of influenza virus hemagglutinin. Virol J 9:91. http://dx.doi.org/10.1186/1743-422X-9-91.
69. Wiley DC, Wilson IA, Skehel JJ. 1981. Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation. Nature 289:373-378. http://dx.doi.org/10.1038/289373a0.
70. Schrödinger, LLC. 2014. The PyMOL molecular graphics system, version 1.7. http://www.pymol.org.
71. Wallace AC, Laskowski RA, Thornton JM. 1995. LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng 8:127-134. http://dx.doi.org/10.1093/protein/8.2.127.