Crystal structure of the swine-origin A (H1N1) — 2009 influenza A virus hemagglutinin (HA) reveals similar antigenicity to that of the 1918 pandemic virus

Abstract

Influenza virus is the causative agent of the seasonal and occasional pandemic flu. The current H1N1 influenza pandemic, announced by the WHO in June 2009, is highly contagious and responsible for global economic losses and fatalities. Although the H1N1 gene segments have three origins in terms of host species, the virus has been named swine-origin influenza virus (S-OIV) due to a predominant swine origin. 2009 S-OIV has been shown to highly resemble the 1918 pandemic virus in many aspects. Hemagglutinin is responsible for the host range and receptor binding of the virus and is therefore a primary indicator for the potential of infection. Primary sequence analysis of the 2009 S-OIV haemagglutinin (HA) reveals its closest relationship to that of the 1918 pandemic influenza virus, however, analysis at the structural level is necessary to critically assess the functional significance. In this report, we report the crystal structure of soluble haemagglutinin H1 (09H1) at 2.9 ?, illustrating that the 09H1 is very similar to the 1918 pandemic HA (18H1) in overall structure and the structural modules, including the five defined antiboby(Ab)-binding epitopes. Our results provide an explanation as to why sera from the survivors of the 1918 pandemics can neutralize the 2009 S-OIV, and people born around the 1918 are resistant to the current pandemic, yet younger generations are more susceptible to the 2009 pandemic.

Keywords

Influenza virus / pandemic / 2009 / 1918 / S-OIV / haemagglutinin (HA) / structure

References

[1] Adams, P.D., Grosse-Kunstleve, R.W., Hung, L.W., Ioerger, T.R., McCoy, A.J., Moriarty, N.W., Read, R.J., Sacchettini, J.C., Sauter, N.K., and Terwilliger, T.C. (2002). PHENIX: building new software for automated crystallographic structure determination. Acta Crystallogr D Biol Crystallogr 58, 1948–1954 .
[2] Caton, A.J., Brownlee, G.G., Yewdell, J.W., and Gerhard, W. (1982). The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (H1 subtype). Cell 31, 417–427 .10.1016/0092-8674(82)90135-0
[3] Centers for Disease Control and Prevention (CDC). (2009). Outbreak of swine-origin influenza A (H1N1) virus infection- Mexico, March-April 2009. MMWR Morb Mortal Wkly Rep 58, 467–470 .
[4] Chang, L.Y., Shih, S.R., Shao, P.L., Huang, D.T., and Huang, L.M. (2009). Novel swine-origin influenza virus A (H1N1): the first pandemic of the 21st century. J Formos Med Assoc 108, 526–532 .10.1016/S0929-6646(09)60369-7
[5] Chen, J., Lee, K.H., Steinhauer, D.A., Stevens, D.J., Skehel, J.J., and Wiley, D.C. (1998). Structure of the hemagglutinin precursor cleavage site, a determinant of influenza pathogenicity and the origin of the labile conformation. Cell 95, 409–417 .10.1016/S0092-8674(00)81771-7
[6] Collaborative Computational Project, Number 4. (1994). The CCP4 suite: programs for protein crystallography. Acta Crystallogr D Biol Crystallogr 50, 760–763 .10.1107/S0907444994003112
[7] Dawood, F.S., Jain, S., Finelli, L., Shaw, M.W., Lindstrom, S., Garten, R.J., Gubareva, L.V., Xu, X., Bridges, C.B., and Uyeki, T.M., and the Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team. (2009). Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 360, 2605–2615 .
[8] Ekiert, D.C., Bhabha, G., Elsliger, M.A., Friesen, R.H., Jongeneelen, M., Throsby, M., Goudsmit, J., and Wilson, I.A. (2009). Antibody recognition of a highly conserved influenza virus epitope. Science 324, 246–251 .10.1126/science.1171491
[9] Emsley, P., and Cowtan, K. (2004). Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr 60, 2126–2132 .10.1107/S0907444904019158
[10] Fields, B.N., Knipe, D.M., and Howley, P.M. (2007). Fields virology, 5th edn (Philadelphia, Wolters Kluwer Health/Lippincott Williams & Wilkins).
[11] Gamblin, S.J., Haire, L.F., Russell, R.J., Stevens, D.J., Xiao, B., Ha, Y., Vasisht, N., Steinhauer, D.A., Daniels, R.S., Elliot, A., . (2004). The structure and receptor binding properties of the 1918 influenza hemagglutinin. Science 303, 1838–1842 .10.1126/science.1093155
[12] Gao, G.F., and Sun, Y.P. (2010). It is not just AIV: From avian to swine-origin influenza virus. Sci China C Life Sci 53, 151–153 .10.1007/s11427-010-0017-4
[13] Igarashi, M., Ito, K., Yoshida, R., Tomabechi, D., Kida, H., Takada, A., and Belshaw, R. (2010). Predicting the antigenic structure of the pandemic (H1N1) 2009 influenza virus hemagglutinin. PLoS ONE 5, e8553.10.1371/journal.pone.0008553
[14] Itoh, Y., Shinya, K., Kiso, M., Watanabe, T., Sakoda, Y., Hatta, M., Muramoto, Y., Tamura, D., Sakai-Tagawa, Y., Noda, T., . (2009). In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. Nature 460, 1021–1025 .
[15] Laskowski, R.A., MacArthur, M.W., Moss, D.S., and Thornton, J.M. (1993). PROCHECK: A program to check the stereochemical quality of protein structures. J Appl Cryst 26, 283–291 .10.1107/S0021889892009944
[16] Lin, T., Wang, G., Li, A., Zhang, Q., Wu, C., Zhang, R., Cai, Q., Song, W., and Yuen, K.Y. (2009). The hemagglutinin structure of an avian H1N1 influenza A virus. Virology 392, 73–81 .10.1016/j.virol.2009.06.028
[17] Liu, D., Liu, X., Yan, J., Liu, W.J., and Gao, G.F. (2009). Interspecies transmission and host restriction of avian H5N1 influenza virus. Sci China C Life Sci 52, 428–438 .10.1007/s11427-009-0062-z
[18] Murshudov, G.N., Vagin, A.A., and Dodson, E.J. (1997). Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr D Biol Crystallogr 53, 240–255 .10.1107/S0907444996012255
[19] Neumann, G., Noda, T., and Kawaoka, Y. (2009). Emergence and pandemic potential of swine-origin H1N1 influenza virus. Nature 459, 931–939 .10.1038/nature08157
[20] Otwinowski, Z., and Minor, W. (1997). Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol 276, 307–326 .10.1016/S0076-6879(97)76066-X
[21] Read, R.J. (2001). Pushing the boundaries of molecular replacement with maximum likelihood. Acta Crystallogr D Biol Crystallogr 57, 1373–1382 .10.1107/S0907444901012471
[22] Shen, J., Ma, J., Wang, Q., and Martin, D.P. (2009). Evolutionary trends of A(H1N1) influenza virus hemagglutinin since 1918. PLoS ONE 4, e7789.10.1371/journal.pone.0007789
[23] Skehel, J.J., and Wiley, D.C. (2000). Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annu Rev Biochem 69, 531–569 .10.1146/annurev.biochem.69.1.531
[24] Smith, G.J., Vijaykrishna, D., Bahl, J., Lycett, S.J., Worobey, M., Pybus, O.G., Ma, S.K., Cheung, C.L., Raghwani, J., Bhatt, S., . (2009). Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic. Nature 459, 1122–1125 .10.1038/nature08182
[25] Stevens, J., Corper, A.L., Basler, C.F., Taubenberger, J.K., Palese, P., and Wilson, I.A. (2004). Structure of the uncleaved human H1 hemagglutinin from the extinct 1918 influenza virus. Science 303, 1866–1870 .10.1126/science.1093373
[26] Stevens, J., Blixt, O., Tumpey, T.M., Taubenberger, J.K., Paulson, J.C., and Wilson, I.A. (2006). Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus. Science 312, 404–410 .10.1126/science.1124513
[27] Sugita, S., Yoshioka, Y., Itamura, S., Kanegae, Y., Oguchi, K., Gojobori, T., Nerome, K., and Oya, A. (1991). Molecular evolution of hemagglutinin genes of H1N1 swine and human influenza A viruses. J Mol Evol 32, 16–23 .10.1007/BF02099924
[28] Yeping Sun, Yi Shi, Wei Zhang, Qing Li, Di Liu, Christopher Vavricka, Jinghua Yan, and Gao, G.F. (2010). In-silicon characterization of the functional and structural modules of the haemagglutinin protein from the swine-origin influenza virus A (H1N1)-2009. Sci China C Life Sci .
[29] Wei, C.J., Boyington, J.C., Dai, K., Houser, K.V., Pearce, M.B., Kong, W.P., Yang, Z.Y., Tumpey, T.M., and Nabel, G.J. (2010). Cross-neutralization of 1918 and 2009 influenza viruses: role of glycans in viral evolution and vaccine design. Sci Transl Med 2, 24ra21.
[30] WHO (2009). World now at the start of 2009 influenza pandemic.
[31] Wilson, I.A., Skehel, J.J., and Wiley, D.C. (1981). Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 A resolution. Nature 289, 366–373 .10.1038/289366a0
[32] Xu, R., Ekiert, D.C., Krause, J.C., Hai, R., Crowe, J.E. Jr, and Wilson, I.A. (2010). Structural Basis of Preexisting Immunity to the 2009 H1N1 Pandemic Influenza Virus. Science 328, 357–60 .10.1126/science.1186430
[33] Yang, Y., Sugimoto, J.D., Halloran, M.E., Basta, N.E., Chao, D.L., Matrajt, L., Potter, G., Kenah, E., and Longini, I.M. Jr. (2009). The transmissibility and control of pandemic influenza A (H1N1) virus. Science 326, 729–733 .10.1126/science.1177373