Skip to main content
Wiley - PMC COVID-19 Collection logoLink to Wiley - PMC COVID-19 Collection
. 2009 Jun 23;81(8):1457–1470. doi: 10.1002/jmv.21531

Influenza A virus in Taiwan, 1980–2006: Phylogenetic and antigenic characteristics of the hemagglutinin gene

Sheng‐Fan Wang 1,2, Yuan‐Ming Lee 2,3,4,10, Yu‐Jiun Chan 3,4,5, Hsin‐Fu Liu 3,6, Yung‐Fong Yen 7, Wu‐Tse Liu 1, Jason C Huang 1,2,8,, Yi‐Ming Arthur Chen 2,3,9,
PMCID: PMC7166446  PMID: 19551820

Abstract

Limited amount of information is available in Taiwan on the genetic or antigenic characteristics of influenza A virus prior to the establishment of a Taiwan surveillance network in 2000. Isolates of H1N1 and H3N2 viruses in Taiwan between 1980 and 2006 were studied, and part of the hemagglutinin gene was analyzed due to its importance in terms of viral infection and antibody neutralization. Results from a phylogenetic analysis indicate continuous evolutionary topology in H3N2 isolates, and two distinct H1N1 lineages. Many genetic relationships between vaccine strains and epidemic isolates appearing in Taiwan before other global locations were also observed and recorded in addition to a gradual increase in the number of N‐linked glycosylation sites on partial HA1 proteins since 1980. The results from pairwise comparisons of HA1 nucleotide and deduced amino acid sequences indicate shared identities within groups organized according to their bootstrap and P‐values of approximately 95.5–100% and 95.7–100% in H1N1 and 94.5–100% and 93.2–100% in H3N2 viruses, respectively. Comparisons of amino acid substitutions in the five antigenic regions reveal highly non‐synonymous changes occurring in the Sb region of H1N1 and in the B region of H3N2. The results of an antigenic analysis using a hemagglutinin inhibition (HI) test indicate the presence of some epidemic strains 1–2 years earlier in Taiwan than in other parts of the world, as well as higher vaccine mismatch rates. This information supports the need for continuous surveillance of emerging influenza viruses in Taiwan, which will be useful for making global vaccine decisions. J. Med. Virol. 81:1457–1470, 2009. © 2009 Wiley‐Liss, Inc.

Keywords: H1N1, H3N2, influenza, phylogenetic analysis, hemagglutinin

Contributor Information

Jason C. Huang, Email: jchuang2@ym.edu.tw.

Yi‐Ming Arthur Chen, Email: arthur@ym.edu.tw.

REFERENCES

  1. Abe Y, Takashita E, Sugawara K, Matsuzaki Y, Muraki Y, Hongo S. 2004. Effect of the addition of oligosaccharides on the biological activities and antigenicity of influenza A/H3N2 virus hemagglutinin. J Virol 78: 9605–9611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Abed Y, Hardy I, Li Y, Boivin G. 2002. Divergent evolution of hemagglutinin and neuraminidase genes in recent influenza A:H3N2 viruses isolated in Canada. J Med Virol 67: 589–595. [DOI] [PubMed] [Google Scholar]
  3. Bashirova AA, Geijtenbeek TB, van Duijnhoven GC, van Vliet SJ, Eilering JB, Martin MP, Wu L, Martin TD, Viebig N, Knolle PA, KewalRamani VN, van Kooyk Y, Carrington M. 2001. A dendritic cell‐specific intercellular adhesion molecule 3‐grabbing nonintegrin (DC‐SIGN)‐related protein is highly expressed on human liver sinusoidal endothelial cells and promotes HIV‐1 infection. J Exp Med 193: 671–678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bragstad K, Nielsen LP, Fomsgaard A. 2008. The evolution of human influenza A viruses from 1999 to 2006: A complete genome study. Virol J 5: 40. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carrat F, Flahault A. 2007. Influenza vaccine: The challenge of antigenic drift. Vaccine 25: 6852–6862. [DOI] [PubMed] [Google Scholar]
  6. Chan CH, Lin KL, Chan Y, Wang YL, Chi YT, Tu HL, Shieh HK, Liu WT. 2006. Amplification of the entire genome of influenza A virus H1N1 and H3N2 subtypes by reverse‐transcription polymerase chain reaction. J Virol Methods 136: 38–43. [DOI] [PubMed] [Google Scholar]
  7. Cox NJ, Bai ZS, Kendal AP. 1983. Laboratory‐based surveillance of influenza A(H1N1) and A(H3N2) viruses in 1980–81: Antigenic and genomic analyses. Bull World Health Organ 61: 143–152. [PMC free article] [PubMed] [Google Scholar]
  8. de Jong JC, Beyer WE, Palache AM, Rimmelzwaan GF, Osterhaus AD. 2000. Mismatch between the 1997/1998 influenza vaccine and the major epidemic A(H3N2) virus strain as the cause of an inadequate vaccine‐induced antibody response to this strain in the elderly. J Med Virol 61: 94–99. [PubMed] [Google Scholar]
  9. Fournillier A, Wychowski C, Boucreux D, Baumert TF, Meunier JC, Jacobs D, Muguet S, Depla E, Inchauspe G. 2001. Induction of hepatitis C virus E1 envelope protein‐specific immune response can be enhanced by mutation of N‐glycosylation sites. J Virol 75: 12088–12097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gerhard W, Yewdell J, Frankel ME, Webster R. 1981. Antigenic structure of influenza virus haemagglutinin defined by hybridoma antibodies. Nature 290: 713–717. [DOI] [PubMed] [Google Scholar]
  11. Glezen WP, Taber LH, Frank AL, Gruber WC, Piedra PA. 1997. Influenza virus infections in infants. Pediatr Infect Dis J 16: 1065–1068. [DOI] [PubMed] [Google Scholar]
  12. Goffard A, Callens N, Bartosch B, Wychowski C, Cosset FL, Montpellier C, Dubuisson J. 2005. Role of N‐linked glycans in the functions of hepatitis C virus envelope glycoproteins. J Virol 79: 8400–8409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hanna SL, Pierson TC, Sanchez MD, Ahmed AA, Murtadha MM, Doms RW. 2005. N‐linked glycosylation of west nile virus envelope proteins influences particle assembly and infectivity. J Virol 79: 13262–13274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hay AJ, Gregory V, Douglas AR, Lin YP. 2001. The evolution of human influenza viruses. Philos Trans R Soc Lond 356: 1861–1870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hillis DM. 1997. Phylogenetic analysis. Curr Biol 7: R129–R131. [DOI] [PubMed] [Google Scholar]
  16. Hillis DM. 1998. Taxonomic sampling, phylogenetic accuracy, and investigator bias. Syst Biol 47: 3–8. [DOI] [PubMed] [Google Scholar]
  17. Hoffmann E, Stech J, Guan Y, Webster RG, Perez DR. 2001. Universal primer set for the full‐length amplification of all influenza A viruses. Arch Virol 146: 2275–2289. [DOI] [PubMed] [Google Scholar]
  18. Hsieh YC, Chen HY, Yen JJ, Liu DP, Chang LY, Lu CY, Shao PL, Lee CY, Huang LM. 2005. Influenza in Taiwan: Seasonality and vaccine strain match. J Microbiol Immunol Infect 38: 238–243. [PubMed] [Google Scholar]
  19. Ikic D, Smerdel S, Manhalter T, Pasini N, Delimar N. 1977. HI antibody response in volunteers vaccinated with live influenza A/New Jersey/76 vaccine. Dev Biol Stand 39: 67–71. [PubMed] [Google Scholar]
  20. Jian JW, Chen GW, Lai CT, Hsu LC, Chen PJ, Kuo SH, Wu HS, Shih SR. 2008. Genetic and epidemiological analysis of influenza virus epidemics in Taiwan during 2003 to 2006. J Clin Microbiol 46: 1426–1434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kendal AP, Phillips DJ, Webster RG, Galland GG, Reimer CB. 1981. Effect of test system on the ability of monoclonal antibodies to detect antigenic drift in influenza A(H1N1) virus haemagglutinins. J Gen Virol 54: 253–261. [DOI] [PubMed] [Google Scholar]
  22. Kumar S, Tamura K, Nei M. 2004. MEGA3: Integrated software for molecular evolutionary genetics analysis and sequence alignment. Brief Bioinform 5: 150–163. [DOI] [PubMed] [Google Scholar]
  23. Lan YC, Liu TT, Yang JY, Lee CM, Chen YJ, Chan YJ, Lu JJ, Liu HF, Hsiung CA, Ho MS, Hsiao KJ, Chen HY, Chen YM. 2005. Molecular epidemiology of severe acute respiratory syndrome‐associated coronavirus infections in Taiwan. J Infect Dis 191: 1478–1489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lin YT, Lan YC, Chen YJ, Huang YH, Lee CM, Liu TT, Wong WW, Yang JY, Wang CT, Chen YM. 2007. Molecular epidemiology of HIV‐1 infection and full‐length genomic analysis of circulating recombinant form 07_BC strains from injection drug users in Taiwan. J Infect Dis 195: 1283–1293. [DOI] [PubMed] [Google Scholar]
  25. Lin JH, Chiu SC, Lee CH, Su YJ, Tsai HC, Peng YT, Wu HS. 2008. Genetic and antigenic analysis of epidemic influenza viruses isolated during 2006‐2007 season in Taiwan. J Med Virol 80: 316–322. [DOI] [PubMed] [Google Scholar]
  26. Nicholson KG, Wood JM, Zambon M. 2003. Influenza. Lancet 362: 1733–1745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ohuchi M, Orlich M, Ohuchi R, Simpson BE, Garten W, Klenk HD, Rott R. 1989. Mutations at the cleavage site of the hemagglutinin after the pathogenicity of influenza virus A/chick/Penn/83 (H5N2). Virology 168: 274–280. [DOI] [PubMed] [Google Scholar]
  28. Ohuchi M, Feldmann A, Ohuchi R, Klenk HD. 1995. Neuraminidase is essential for fowl plague virus hemagglutinin to show hemagglutinating activity. Virology 212: 77–83. [DOI] [PubMed] [Google Scholar]
  29. Plotkin JB, Dushoff J. 2003. Codon bias and frequency‐dependent selection on the hemagglutinin epitopes of influenza A virus. Proc Natl Acad Sci USA 100: 7152–7157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Pontoriero AV, Baumeister EG, Campos AM, Savy VL, Lin YP, Hay A. 2003. Antigenic and genomic relation between human influenza viruses that circulated in Argentina in the period 1995‐1999 and the corresponding vaccine components. J Clin Virol 28: 130–140. [DOI] [PubMed] [Google Scholar]
  31. Reading PC, Miller JL, Anders EM. 2000. Involvement of the mannose receptor in infection of macrophages by influenza virus. J Virol 74: 5190–5197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Redlberger M, Aberle SW, Heinz FX, Popow‐Kraupp T. 2007. Dynamics of antigenic and genetic changes in the hemagglutinins of influenza A/H3N2 viruses of three consecutive seasons (2002/2003 to 2004/2005) in Austria. Vaccine 25: 6061–6069. [DOI] [PubMed] [Google Scholar]
  33. Roberts PC, Garten W, Klenk HD. 1993. Role of conserved glycosylation sites in maturation and transport of influenza A virus hemagglutinin. J Virol 67: 3048–3060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ruigrok RW, Aitken A, Calder LJ, Martin SR, Skehel JJ, Wharton SA, Weis W, Wiley DC. 1988. Studies on the structure of the influenza virus haemagglutinin at the pH of membrane fusion. J Gen Virol 69: 2785–2795. [DOI] [PubMed] [Google Scholar]
  35. Saito T. 2006. Review on replication cycle of influenza virus. Nippon Rinsho 64: 1803–1807. [PubMed] [Google Scholar]
  36. Sheth MT, Jhala CI. 1976. Seropatterns of influenza HI antibodies. Indian J Pathol Microbiol 19: 1–14. [PubMed] [Google Scholar]
  37. Shih SR, Chen GW, Yang CC, Yang WZ, Liu DP, Lin JH, Chiu SC, Chen HY, Tsao KC, Huang CG, Huang YL, Mok CK, Chen CJ, Lin TY, Wang JR, Kao CL, Lin KH, Chen LK, Eng HL, Liu YC, Chen PY, Lin JS, Wang JH, Lin CW, Chan YJ, Lu JJ, Hsiung CA, Chen PJ, Su IJ. 2005. Laboratory‐based surveillance and molecular epidemiology of influenza virus in Taiwan. J Clin Microbiol 43: 1651–1661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Shih YP, Chen CY, Liu SJ, Chen KH, Lee YM, Chao YC, Chen YM. 2006. Identifying epitopes responsible for neutralizing antibody and DC‐SIGN binding on the spike glycoprotein of the severe acute respiratory syndrome coronavirus. J Virol 80: 10315–10324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Silverstein G. 2006. Preparing for pandemic influenza. Lancet 367: 1239–1240. [DOI] [PubMed] [Google Scholar]
  40. Skehel JJ, Stevens DJ, Daniels RS, Douglas AR, Knossow M, Wilson IA, Wiley DC. 1984. A carbohydrate side chain on hemagglutinins of Hong Kong influenza viruses inhibits recognition by a monoclonal antibody. Proc Natl Acad Sci USA 81: 1779–1783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Skowronski DM, Masaro C, Kwindt TL, Mak A, Petric M, Li Y, Sebastian R, Chong M, Tam T, De Serres G. 2007. Estimating vaccine effectiveness against laboratory‐confirmed influenza using a sentinel physician network: Results from the 2005‐2006 season of dual A and B vaccine mismatch in Canada. Vaccine 25: 2842–2851. [DOI] [PubMed] [Google Scholar]
  42. Smith CB, Cox NJ, Subbarao K, Taber LH, Glezen WP. 2002. Molecular epidemiology of influenza A(H3N2) virus reinfections. J Infect Dis 185: 980–985. [DOI] [PubMed] [Google Scholar]
  43. Tseng RK, Chen HY, Hong CB. 1996. Influenza virus infections in Taiwan from 1979 to 1995. Jpn J Med Sci Biol 49: 77–93. [DOI] [PubMed] [Google Scholar]
  44. Underwood PA, Skehel JJ, Wiley DC. 1987. Receptor‐binding characteristics of monoclonal antibody‐selected antigenic variants of influenza virus. J Virol 61: 206–208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Vigerust DJ, Ulett KB, Boyd KL, Madsen J, Hawgood S, McCullers JA. 2007. N‐linked glycosylation attenuates H3N2 influenza viruses. J Virol 81: 8593–8600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Wang SF, Huang JC, Lee YM, Liu SJ, Chan YJ, Chau YP, Chong P, Chen YM. 2008. DC‐SIGN mediates avian H5N1 influenza virus infection in cis and in trans. Biochem Biophys Res Commun 373: 561–566. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Webster RG, Bean WJ, Gorman OT, Chambers TM, Kawaoka Y. 1992. Evolution and ecology of influenza A viruses. Microbiol Rev 56: 152–179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. 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. [DOI] [PubMed] [Google Scholar]
  49. Zhang M, Gaschen B, Blay W, Foley B, Haigwood N, Kuiken C, Korber B. 2004. Tracking global patterns of N‐linked glycosylation site variation in highly variable viral glycoproteins: HIV, SIV, and HCV envelopes and influenza hemagglutinin. Glycobiology 14: 1229–1246. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Medical Virology are provided here courtesy of Wiley

RESOURCES