Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1992 Feb;66(2):1066–1073. doi: 10.1128/jvi.66.2.1066-1073.1992

Hemagglutinin mutations related to antigenic variation in H1 swine influenza viruses.

S M Luoh 1, M W McGregor 1, V S Hinshaw 1
PMCID: PMC240810  PMID: 1731091

Abstract

The hemagglutinin (HA) of a recent swine influenza virus, A/Sw/IN/1726/88 (H1N1), was shown previously to have four antigenic sites, as determined from analysis of monoclonal antibody (MAb)-selected escape mutants. To define the HA mutations related to these antigenic sites, we cloned and sequenced the HA genes amplified by polymerase chain reaction of parent virus and MAb-selected escape mutants. The genetic data indicated the presence of four amino acid changes. After alignment with the three-dimensional structure of H3 HA, three changes were located on the distal tip of the HA, and the fourth was located within the loop on the HA. We then compared our antigenic sites, as defined by the changed amino acids, with the well-defined sites on the H1 HA of A/PR/8/34. The four amino acid residues corresponded with three antigenic sites on the HA of A/PR/8/34. This finding, in conjunction with our previous antigenic data, indicated that two of the four antigenic sites were overlapping. In addition, our previous studies indicated that one MAb-selected mutant and a recent, naturally occurring swine isolate reacted similarly with the MAb panel. However, their amino acid changes were different and also distant on the primary sequence but close topographically. This finding indicates that changes outside the antigenic site may also affect the site. A comparison of the HA amino acid sequences of early and recent swine isolates showed striking conservation of genetic sequences as well as of the antigenic sites. Thus, swine influenza viruses evolve more slowly than human viruses, possibly because they are not subjected to the same degree of immune selection.

Full text

PDF
1066

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alexander D. J., Parsons G. Protection of chickens against challenge with virulent influenza A viruses of Hav5 subtype conferred by prior infection with influenza A viruses of Hsw1 subtype. Arch Virol. 1980;66(3):265–269. doi: 10.1007/BF01314740. [DOI] [PubMed] [Google Scholar]
  2. Austin F. J., Kawaoka Y., Webster R. G. Molecular analysis of the haemagglutinin gene of an avian H1N1 influenza virus. J Gen Virol. 1990 Oct;71(Pt 10):2471–2474. doi: 10.1099/0022-1317-71-10-2471. [DOI] [PubMed] [Google Scholar]
  3. Austin F. J., Webster R. G. Antigenic mapping of an avian H1 influenza virus haemagglutinin and interrelationships of H1 viruses from humans, pigs and birds. J Gen Virol. 1986 Jun;67(Pt 6):983–992. doi: 10.1099/0022-1317-67-6-983. [DOI] [PubMed] [Google Scholar]
  4. Both G. W., Shi C. H., Kilbourne E. D. Hemagglutinin of swine influenza virus: a single amino acid change pleiotropically affects viral antigenicity and replication. Proc Natl Acad Sci U S A. 1983 Nov;80(22):6996–7000. doi: 10.1073/pnas.80.22.6996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Both G. W., Sleigh M. J., Cox N. J., Kendal A. P. Antigenic drift in influenza virus H3 hemagglutinin from 1968 to 1980: multiple evolutionary pathways and sequential amino acid changes at key antigenic sites. J Virol. 1983 Oct;48(1):52–60. doi: 10.1128/jvi.48.1.52-60.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Caton A. J., Brownlee G. G., Yewdell J. W., Gerhard W. The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (H1 subtype). Cell. 1982 Dec;31(2 Pt 1):417–427. doi: 10.1016/0092-8674(82)90135-0. [DOI] [PubMed] [Google Scholar]
  7. Chambers T. M., Hinshaw V. S., Kawaoka Y., Easterday B. C., Webster R. G. Influenza viral infection of swine in the United States 1988-1989. Arch Virol. 1991;116(1-4):261–265. doi: 10.1007/BF01319247. [DOI] [PubMed] [Google Scholar]
  8. Dacso C. C., Couch R. B., Six H. R., Young J. F., Quarles J. M., Kasel J. A. Sporadic occurrence of zoonotic swine influenza virus infections. J Clin Microbiol. 1984 Oct;20(4):833–835. doi: 10.1128/jcm.20.4.833-835.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gorman O. T., Bean W. J., Kawaoka Y., Webster R. G. Evolution of the nucleoprotein gene of influenza A virus. J Virol. 1990 Apr;64(4):1487–1497. doi: 10.1128/jvi.64.4.1487-1497.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hanahan D. Studies on transformation of Escherichia coli with plasmids. J Mol Biol. 1983 Jun 5;166(4):557–580. doi: 10.1016/s0022-2836(83)80284-8. [DOI] [PubMed] [Google Scholar]
  12. Hauptmann R., Clarke L. D., Mountford R. C., Bachmayer H., Almond J. W. Nucleotide sequence of the haemagglutinin gene of influenza virus A/England/321/77. J Gen Virol. 1983 Jan;64(Pt 1):215–220. doi: 10.1099/0022-1317-64-1-215. [DOI] [PubMed] [Google Scholar]
  13. Hinshaw V. S., Bean W. J., Jr, Webster R. G., Easterday B. C. The prevalence of influenza viruses in swine and the antigenic and genetic relatedness of influenza viruses from man and swine. Virology. 1978 Jan;84(1):51–62. doi: 10.1016/0042-6822(78)90217-9. [DOI] [PubMed] [Google Scholar]
  14. Hinshaw V. S., Webster R. G., Bean W. J., Downie J., Senne D. A. Swine influenza-like viruses in turkeys: potential source of virus for humans? Science. 1983 Apr 8;220(4593):206–208. doi: 10.1126/science.6298942. [DOI] [PubMed] [Google Scholar]
  15. Hinshaw V. S., Webster R. G., Turner B. Novel influenza A viruses isolated from Canadian feral ducks: including strains antigenically related to swine influenza (Hsw1N1) viruses. J Gen Virol. 1978 Oct;41(1):115–127. doi: 10.1099/0022-1317-41-1-115. [DOI] [PubMed] [Google Scholar]
  16. Katz J. M., Webster R. G. Antigenic and structural characterization of multiple subpopulations of H3N2 influenza virus from an individual. Virology. 1988 Aug;165(2):446–456. doi: 10.1016/0042-6822(88)90588-0. [DOI] [PubMed] [Google Scholar]
  17. Kawaoka Y., Yamnikova S., Chambers T. M., Lvov D. K., Webster R. G. Molecular characterization of a new hemagglutinin, subtype H14, of influenza A virus. Virology. 1990 Dec;179(2):759–767. doi: 10.1016/0042-6822(90)90143-f. [DOI] [PubMed] [Google Scholar]
  18. Kilbourne E. D., McGregor S., Easterday B. C. Hemagglutinin mutants of swine influenza virus differing in replication characteristics in their natural host. Infect Immun. 1979 Oct;26(1):197–201. doi: 10.1128/iai.26.1.197-201.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lubeck M. D., Gerhard W. Topological mapping antigenic sites on the influenza A/PR/8/34 virus hemagglutinin using monoclonal antibodies. Virology. 1981 Aug;113(1):64–72. doi: 10.1016/0042-6822(81)90136-7. [DOI] [PubMed] [Google Scholar]
  20. Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Messing J. New M13 vectors for cloning. Methods Enzymol. 1983;101:20–78. doi: 10.1016/0076-6879(83)01005-8. [DOI] [PubMed] [Google Scholar]
  22. Orlich M., Khátchikian D., Teigler A., Rott R. Structural variation occurring in the hemagglutinin of influenza virus A/turkey/Oregon/71 during adaptation to different cell types. Virology. 1990 Jun;176(2):531–538. doi: 10.1016/0042-6822(90)90023-k. [DOI] [PubMed] [Google Scholar]
  23. Parry N., Fox G., Rowlands D., Brown F., Fry E., Acharya R., Logan D., Stuart D. Structural and serological evidence for a novel mechanism of antigenic variation in foot-and-mouth disease virus. Nature. 1990 Oct 11;347(6293):569–572. doi: 10.1038/347569a0. [DOI] [PubMed] [Google Scholar]
  24. Philpott M., Hioe C., Sheerar M., Hinshaw V. S. Hemagglutinin mutations related to attenuation and altered cell tropism of a virulent avian influenza A virus. J Virol. 1990 Jun;64(6):2941–2947. doi: 10.1128/jvi.64.6.2941-2947.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Raymond F. L., Caton A. J., Cox N. J., Kendal A. P., Brownlee G. G. Antigenicity and evolution amongst recent influenza viruses of H1N1 subtype. Nucleic Acids Res. 1983 Oct 25;11(20):7191–7203. doi: 10.1093/nar/11.20.7191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Raymond F. L., Caton A. J., Cox N. J., Kendal A. P., Brownlee G. G. The antigenicity and evolution of influenza H1 haemagglutinin, from 1950-1957 and 1977-1983: two pathways from one gene. Virology. 1986 Jan 30;148(2):275–287. doi: 10.1016/0042-6822(86)90325-9. [DOI] [PubMed] [Google Scholar]
  27. Robertson J. S., Bootman J. S., Newman R., Oxford J. S., Daniels R. S., Webster R. G., Schild G. C. Structural changes in the haemagglutinin which accompany egg adaptation of an influenza A(H1N1) virus. Virology. 1987 Sep;160(1):31–37. doi: 10.1016/0042-6822(87)90040-7. [DOI] [PubMed] [Google Scholar]
  28. Rota P. A., Rocha E. P., Harmon M. W., Hinshaw V. S., Sheerar M. G., Kawaoka Y., Cox N. J., Smith T. F. Laboratory characterization of a swine influenza virus isolated from a fatal case of human influenza. J Clin Microbiol. 1989 Jun;27(6):1413–1416. doi: 10.1128/jcm.27.6.1413-1416.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Schild G. C., Oxford J. S., de Jong J. C., Webster R. G. Evidence for host-cell selection of influenza virus antigenic variants. Nature. 1983 Jun 23;303(5919):706–709. doi: 10.1038/303706a0. [DOI] [PubMed] [Google Scholar]
  30. Sheerar M. G., Easterday B. C., Hinshaw V. S. Antigenic conservation of H1N1 swine influenza viruses. J Gen Virol. 1989 Dec;70(Pt 12):3297–3303. doi: 10.1099/0022-1317-70-12-3297. [DOI] [PubMed] [Google Scholar]
  31. Tindall K. R., Kunkel T. A. Fidelity of DNA synthesis by the Thermus aquaticus DNA polymerase. Biochemistry. 1988 Aug 9;27(16):6008–6013. doi: 10.1021/bi00416a027. [DOI] [PubMed] [Google Scholar]
  32. Webster R. G., Hinshaw V. S., Laver W. G. Selection and analysis of antigenic variants of the neuraminidase of N2 influenza viruses with monoclonal antibodies. Virology. 1982 Feb;117(1):93–104. doi: 10.1016/0042-6822(82)90510-4. [DOI] [PubMed] [Google Scholar]
  33. Wiley D. C., Skehel J. J. The structure and function of the hemagglutinin membrane glycoprotein of influenza virus. Annu Rev Biochem. 1987;56:365–394. doi: 10.1146/annurev.bi.56.070187.002053. [DOI] [PubMed] [Google Scholar]
  34. Wiley D. C., Wilson I. A., Skehel J. J. Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation. Nature. 1981 Jan 29;289(5796):373–378. doi: 10.1038/289373a0. [DOI] [PubMed] [Google Scholar]
  35. Wilson I. A., Cox N. J. Structural basis of immune recognition of influenza virus hemagglutinin. Annu Rev Immunol. 1990;8:737–771. doi: 10.1146/annurev.iy.08.040190.003513. [DOI] [PubMed] [Google Scholar]
  36. Winter G., Fields S., Brownlee G. G. Nucleotide sequence of the haemagglutinin gene of a human influenza virus H1 subtype. Nature. 1981 Jul 2;292(5818):72–75. doi: 10.1038/292072a0. [DOI] [PubMed] [Google Scholar]
  37. Yanisch-Perron C., Vieira J., Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. doi: 10.1016/0378-1119(85)90120-9. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES