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. 2006 Jul 21;21(7):511–519. doi: 10.1007/s10654-006-9031-z

Genomic Analysis of Influenza A Viruses, including Avian Flu (H5N1) Strains

Insung Ahn 1,2, Byeong-Jin Jeong 2,3, Se-Eun Bae 2, Jin Jung 2, Hyeon S Son 2,3,4,
PMCID: PMC7088104  PMID: 16858618

Abstract

This study was designed to conduct genomic analysis in two steps, such as the overall relative synonymous codon usage (RSCU) analysis of the five virus species in the orthomyxoviridae family, and more intensive pattern analysis of the four subtypes of influenza A virus (H1N1, H2N2, H3N2, and H5N1) which were isolated from human population. All the subtypes were categorized by their isolated regions, including Asia, Europe, and Africa, and most of the synonymous codon usage patterns were analyzed by correspondence analysis (CA). As a result, influenza A virus showed the lowest synonymous codon usage bias among the virus species of the orthomyxoviridae family, and influenza B and influenza C virus were followed, while suggesting that influenza A virus might have an advantage in transmitting across the species barrier due to their low codon usage bias. The ENC values of the host-specific HA and NA genes represented their different HA and NA types very well, and this reveals that each influenza A virus subtype uses different codon usage patterns as well as the amino acid compositions. In NP, PA and PB2 genes, most of the virus subtypes showed similar RSCU patterns except for H5N1 and H3N2 (A/HK/1774/1999) subtypes which were suspected to be transmitted across the species barrier, from avian and porcine species to human beings, respectively. This distinguishable synonymous codon usage patterns in non-human origin viruses might be useful in determining the origin of influenza A viruses in genomic levels as well as the serological tests. In this study, all the process, including extracting sequences from GenBank flat file and calculating codon usage values, was conducted by Java codes, and these bioinformatics-related methods may be useful in predicting the evolutionary patterns of pandemic viruses.

Keywords: Avian flu, Correspondence analysis, Genomic analysis, Influenza A virus, Synonymous codon usage

Acknowledgments

We acknowledge the contribution of all the experimentalists who made their invaluable data publicly available. This work was supported by the Brain Korea 21 Project in 2006.

References

  • 1.Puthavathana P, Auewarakul P, Charoenying PC, et al. Molecular characterization of the complete genome of human influenza H5N1 virus isolates from Thailand. J␣General Virol. 2005;86:423–433. doi: 10.1099/vir.0.80368-0. [DOI] [PubMed] [Google Scholar]
  • 2.Subbarao K, Shaw MW. Molecular aspects of avian influenza (H5N1) viruses isolated from humans. Rev Med Virol. 2000;10:337–348. doi: 10.1002/1099-1654(200009/10)10:5<337::AID-RMV292>3.0.CO;2-V. [DOI] [PubMed] [Google Scholar]
  • 3.CDC News. 2005. Information about Avian Influenza (Bird Flu) and Avian Influenza A (H5N1) virus. Available at http://www.cdc.gov/flu/avian/gen-info/facts.htm
  • 4.Enserink M. H5N1 moves into Africa, European Union, deepening global crisis. Science. 2006;311:932. doi: 10.1126/science.311.5763.932a. [DOI] [PubMed] [Google Scholar]
  • 5.Lin YP, Shaw M, Gregory V, et al. Avian-to-human transmission of H9N2 subtype influenza A viruses: Relationship between H9N2 and H5N1 human isolates. Proc Natl Acad Sci. 2000;97:9654–9658. doi: 10.1073/pnas.160270697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Dimmock, NJ, Easton, AJ, Leppard KN 2002. Introduction to modern virology. pp. 297–311. Blackwell publishing, 350 Main Street, Malden, MA 02148–5018, USA
  • 7.Liu JP. Avian influenza – a pandemic waiting to happen? J Microbiol Immunol Infect. 2006;39:4–10. [PubMed] [Google Scholar]
  • 8.Voyles BJ 2002, The Biology of Viruses. 2nd edn. McGraw-Hill Companies, Inc. 1221 Avenue of the Americas, New York, USA, pp. 147–149, 338–341
  • 9.Matrosovich M, Zhou N, Kawaoka Y, Webster R. The surface glycoproteins of H5 influenza viruses isolated humans, chickens, and wild aquatic birds have distinguishable properties. J Virol. 1999;73:1146–1155. doi: 10.1128/jvi.73.2.1146-1155.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Plotkin JB, Dushoff J. Codon bias and frequency-dependent selection on the hemagglutinin epitopes of influenza A virus. Proc Natl Acad Sci. 2003;100:7152–7157. doi: 10.1073/pnas.1132114100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Rogers GN, Paulson JC. Receptor determinants of human and animal influenza virus isolates: differences in receptor specificity of the H3 hemagglutinin based on species of origin. Virology. 1983;127:361–373. doi: 10.1016/0042-6822(83)90150-2. [DOI] [PubMed] [Google Scholar]
  • 12.Duret L. Evolution of synonymous codon usage in metazoans. Curr Opin Gene Dev. 2002;12:640–649. doi: 10.1016/S0959-437X(02)00353-2. [DOI] [PubMed] [Google Scholar]
  • 13.Mclnerney JO. Codon. Replicational and transcriptional selection on codon usage in Borrelia burgdorferi. Proc Natl Acad Sci. 1998;95:10698–10703. doi: 10.1073/pnas.95.18.10698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Moriyama EN, Hartl DL. Codon usage bias and base composition of nuclear genes in Drosophila. Genetics. 1993;134:847–858. doi: 10.1093/genetics/134.3.847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Lynn DJ, Singer GAC, Hickey DA. Synonymous codon usage in subject to selection in thermophilic bacteria. Nucleic Acids Res. 2002;30:4272–4277. doi: 10.1093/nar/gkf546. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Shields DC, Sharp PM. Synonymous codon usage in Bacillus stbtilis reflects both translational selection and mutational biases. Nucleic Acids Res. 1987;15:8023–8040. doi: 10.1093/nar/15.19.8023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Stenico M, Lloyd AT, Sharp PM. Codon usage in Caenorhabditis elegans: delineation of translational selection and mutational biases. Nucleic Acids Res. 1994;22:2437–2446. doi: 10.1093/nar/22.13.2437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Gu W, Zhou T, Ma J, Sun X, Lu Z. Analysis of synonymous codon usage in SARS Coronavirus and other viruses in the Nidovirales. Virus Res. 2004;101:155–161. doi: 10.1016/j.virusres.2004.01.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Jenkins GM, Holmes EC. The extent of codon usage bias in human RNA viruses and its evolutionary origin. Virus Res. 2003;92:1–7. doi: 10.1016/S0168-1702(02)00309-X. [DOI] [PubMed] [Google Scholar]
  • 20.Sharp PM, Li WH. Codon usage in regulatory genes in Escherichia coli does not reflect for ‘rare’ codons. Nucleic Acids Res. 1986;14:7737–7749. doi: 10.1093/nar/14.19.7737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Wright F. The ‘effective number of codons’ used in a gene. Gene. 1990;87:23–29. doi: 10.1016/0378-1119(90)90491-9. [DOI] [PubMed] [Google Scholar]
  • 22.Cary NC 2004. SAS®R9.1.2 Qualification Tools User’s Guide. SAS Institute Inc.
  • 23.Johnson RA, Wichern DW Applied Multivariate Statistical Analysis. 5th edn. Prentice-Hall, Inc. 2002
  • 24.Perrière G, Thioulouse J. Use and misuse of correspondence analysis in codon usage studies. Nucleic Acids Res. 2002;30:4548–4555. doi: 10.1093/nar/gkf565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Edler AA. Avian flu (H5N1): its epidemiology, prevention, and implications for anaesthesiology. J Clin Anesth. 2006;18:1–4. doi: 10.1016/j.jclinane.2005.12.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Gregory V, Lim W, Cameron K, et al. Infection of a child in Hong Kong by influenza A h3n2 virus closely related to viruses circulating in European pigs. J Gen Virol. 2001;82:1397–1406. doi: 10.1099/0022-1317-82-6-1397. [DOI] [PubMed] [Google Scholar]
  • 27.Eijk M, White MR, Batenburg JJ, et al. Interactions of influenza A virus with sialic acids present on porcine surfactant protein D. Am J Respir Cell Mol Biol. 2004;30:871–879. doi: 10.1165/rcmb.2003-0355OC. [DOI] [PubMed] [Google Scholar]

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