1887

Abstract

Purpose. Influenza viruses are characterised by high variability, which makes them able to cause annual epidemics. The aim of this study is to determine the antigenic and genetic characteristics of influenza viruses circulating in Bulgaria during the 2016/2017 season.

Methodology. The detection and typing/subtyping of influenza viruses were performed using real time RT-PCR. Results of antigenic characterisation, phylogenetic and amino acid sequence analyses of representative influenza strains are presented herein.

Results. The 2016/2017 season was characterised by an early start, an exclusive dominance of A(H3N2) viruses accounting for 93 % of total influenza virus detections, and a low circulation of A(H1N1)pdm09 (4.2 %) and type B (2.5 %) viruses. The analysed A(H3N2) viruses belonged to subclades 3C.2a (52 %) and 3C.2a1 (48 %); all studied A(H1N1)pdm09 and B/Victoria-lineage viruses belonged to subclades 6B.1 and 1A, respectively. The amino acid sequence analysis of 56 A(H3N2) isolates revealed the presence of substitutions in 18 positions in haemagglutinin (HA) as compared to the A/Hong Kong/4801/2014 vaccine virus, seven of which occurred in four antigenic sites, together with changes in 23 positions in neuraminidase (NA), and a number of substitutions in internal proteins PB2, PB1, PB1-F2, PA, NP and NS1. Despite the many amino acid substitutions, A(H3N2) viruses remained antigenically similar to the vaccine strain. Substitutions in HA and NA sequences of A(H1N1)pdm09 and B/Victoria-lineage strains were also identified, including in antigenic sites.

Conclusion. The results of this study confirm the genetic variability of circulating influenza viruses, particularly A(H3N2), and the need for continued antigenic and molecular surveillance.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.000668
2018-01-03
2019-10-17
Loading full text...

Full text loading...

/deliver/fulltext/jmm/67/2/228.html?itemId=/content/journal/jmm/10.1099/jmm.0.000668&mimeType=html&fmt=ahah

References

  1. WHO 2014; Influenza (Seasonal) Fact Sheet N°211. Available onlinewww.who.int/mediacentre/factsheets/fs211/en/# [accessed on 12 July 2014]
  2. Tong S, Zhu X, Li Y, Shi M, Zhang J et al. New world bats harbor diverse influenza A viruses. PLoS Pathog 2013;9:e1003657 [CrossRef][PubMed]
    [Google Scholar]
  3. Wiley DC, Skehel JJ. The structure and function of the hemagglutinin membrane glycoprotein of influenza virus. Annu Rev Biochem 1987;56:365–394 [CrossRef][PubMed]
    [Google Scholar]
  4. Skehel JJ, Wiley DC. Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annu Rev Biochem 2000;69:531–569 [CrossRef][PubMed]
    [Google Scholar]
  5. Wiley DC, Wilson IA, Skehel JJ. Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation. Nature 1981;289:373–378 [CrossRef][PubMed]
    [Google Scholar]
  6. Caton AJ, Brownlee GG, Yewdell JW, Gerhard W. The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (H1 subtype). Cell 1982;31:417–427 [CrossRef][PubMed]
    [Google Scholar]
  7. Wilson IA, Cox NJ. Structural basis of immune recognition of influenza virus hemagglutinin. Annu Rev Immunol 1990;8:737–787 [CrossRef][PubMed]
    [Google Scholar]
  8. Krystal M, Young JF, Palese P, Wilson IA, Skehel JJ et al. Sequential mutations in hemagglutinins of influenza B virus isolates: definition of antigenic domains. Proc Natl Acad Sci USA 1983;80:4527–4531 [CrossRef][PubMed]
    [Google Scholar]
  9. Jin H, Zhou H, Liu H, Chan W, Adhikary L et al. Two residues in the hemagglutinin of A/Fujian/411/02-like influenza viruses are responsible for antigenic drift from A/Panama/2007/99. Virology 2005;336:113–119 [CrossRef][PubMed]
    [Google Scholar]
  10. Koel BF, Burke DF, Bestebroer TM, van der Vliet S, Zondag GC et al. Substitutions near the receptor binding site determine major antigenic change during influenza virus evolution. Science 2013;342:976–979 [CrossRef][PubMed]
    [Google Scholar]
  11. Skehel JJ, Stevens DJ, Daniels RS, Douglas AR, Knossow M et al. A carbohydrate side chain on hemagglutinins of Hong Kong influenza viruses inhibits recognition by a monoclonal antibody. Proc Natl Acad Sci USA 1984;81:1779–1783 [CrossRef][PubMed]
    [Google Scholar]
  12. WHO 2011; Manual for the laboratory diagnosis and virological surveillance of influenza. Available onlinehttp://whqlibdoc.who.int/publications/2011/9789241548090_eng.pdf
  13. Kodani M, Yang G, Conklin LM, Travis TC, Whitney CG et al. Application of TaqMan low-density arrays for simultaneous detection of multiple respiratory pathogens. J Clin Microbiol 2011;49:2175–2182 [CrossRef][PubMed]
    [Google Scholar]
  14. Lu X, Chittaganpitch M, Olsen SJ, Mackay IM, Sloots TP et al. Real-time PCR assays for detection of bocavirus in human specimens. J Clin Microbiol 2006;44:3231–3235 [CrossRef][PubMed]
    [Google Scholar]
  15. Matrosovich M, Matrosovich T, Carr J, Roberts NA, Klenk HD. Overexpression of the α-2,6-sialyltransferase in MDCK cells increases influenza virus sensitivity to neuraminidase inhibitors. J Virol 2003;77:8418–8425 [CrossRef][PubMed]
    [Google Scholar]
  16. Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: molecular evolutionary genetics analysis version 6.0. Mol Biol Evol 2013;30:2725–2729 [CrossRef][PubMed]
    [Google Scholar]
  17. ECDC Surveillance Report Influenza virus characterisation Summary Europe, July 2017. Available onlinehttps://ecdc.europa.eu/sites/portal/files/documents/ERLI-Net-report-Jul-2017.pdf
  18. Fang Q, Gao Y, Chen M, Guo X, Yang X et al. Molecular epidemiology and evolution of A(H1N1)pdm09 and H3N2 virus during winter 2012–2013 in Beijing, China. Infect Genet Evol 2014;26:228–240 [CrossRef][PubMed]
    [Google Scholar]
  19. Broberg E, Melidou A, Prosenc K, Bragstad K, Hungnes O. Predominance of influenza A(H1N1)pdm09 virus genetic subclade 6B.1 and influenza B/Victoria lineage viruses at the start of the 2015/16 influenza season in Europe. Euro Surveill 2016;21:30184 [CrossRef]
    [Google Scholar]
  20. Igarashi M, Ito K, Yoshida R, Tomabechi D, Kida H et al. Predicting the antigenic structure of the pandemic (H1N1) 2009 influenza virus hemagglutinin. PLoS One 2010;5:e8553 [CrossRef][PubMed]
    [Google Scholar]
  21. Yang H, Carney P, Stevens J. Structure and receptor binding properties of a pandemic H1N1 virus hemagglutinin. PLoS Curr 2010;2:RRN1152 [CrossRef][PubMed]
    [Google Scholar]
  22. de Graaf M, Fouchier RA. Role of receptor binding specificity in influenza A virus transmission and pathogenesis. Embo J 2014;33:823–841 [CrossRef][PubMed]
    [Google Scholar]
  23. Korsun N, Angelova S, Gregory V, Daniels R, Georgieva I et al. Antigenic and genetic characterization of influenza viruses circulating in Bulgaria during the 2015/2016 season. Infect Genet Evol 2017;49:241–250 [CrossRef][PubMed]
    [Google Scholar]
  24. WHO 2016; Summary of neuraminidase amino acid substitutions associated with reduced inhibition by neuraminidase inhibitors (NAI). Available onlinewww.who.int/influenza/gisrs_laboratory/antiviral_susceptibility/nai_overview/en/ [Last updated 21 October 2016]
  25. Laplante J, St George K. Antiviral resistance in influenza viruses: laboratory testing. Clin Lab Med 2014;34:387–408 [CrossRef][PubMed]
    [Google Scholar]
  26. Melidou A, Broberg E.European region influenza surveillance network Predominance of influenza A(H3N2) virus genetic subclade 3C.2a1 during an early 2016/17 influenza season in Europe - Contribution of surveillance data from World Health Organization (WHO) European region to the WHO vaccine composition consultation for northern hemisphere 2017/18. Vaccine 2017;35:4828–4835 [CrossRef][PubMed]
    [Google Scholar]
  27. Korsun N, Angelova S, Teodosieva A. Virological surveillance of influenza in four recent post-pandemic seasons (2010/11 to 2013/14) in Bulgaria. Cent Eur J Public Health 2016;24:180–187 [CrossRef][PubMed]
    [Google Scholar]
  28. Stucker KM, Schobel SA, Olsen RJ, Hodges HL, Lin X et al. Haemagglutinin mutations and glycosylation changes shaped the 2012/13 influenza A(H3N2) epidemic, Houston, Texas. Euro Surveill 2015;20:21122 [CrossRef][PubMed]
    [Google Scholar]
  29. Chambers BS, Parkhouse K, Ross TM, Alby K, Hensley SE. Identification of hemagglutinin residues responsible for H3N2 antigenic drift during the 2014–2015 influenza season. Cell Rep 2015;12:1–6 [CrossRef][PubMed]
    [Google Scholar]
  30. Broberg E, Snacken R, Adlhoch C, Beauté J, Galinska M et al. Start of the 2014/15 influenza season in Europe: drifted influenza A(H3N2) viruses circulate as dominant subtype. Euro Surveill 2015;20:21023 [CrossRef][PubMed]
    [Google Scholar]
  31. WHO 2017; Worldwide Influenza Centre, London. February 2017 Interim Report. Report prepared for the WHO annual consultation on the composition of influenza vaccine for the northern hemisphere 2017–2018, 27 February–1 March 2017 London: Francis Crick Institute; Available onlinehttps://www.crick.ac.uk/media/358671/crick_nh_vcm_report_feb_2017_v2.pdf
    [Google Scholar]
  32. Glatman-Freedman A, Drori Y, Beni SA, Friedman N, Pando R et al. Genetic divergence of Influenza A(H3N2) amino acid substitutions mark the beginning of the 2016–2017 winter season in Israel. J Clin Virol 2017;93:71–75 [CrossRef][PubMed]
    [Google Scholar]
  33. Ferguson NM, Galvani AP, Bush RM. Ecological and immunological determinants of influenza evolution. Nature 2003;422:428–433 [CrossRef][PubMed]
    [Google Scholar]
  34. Popova L, Smith K, West AH, Wilson PC, James JA et al. Immunodominance of antigenic site B over site A of hemagglutinin of recent H3N2 influenza viruses. PLoS One 2012;7:e41895 [CrossRef][PubMed]
    [Google Scholar]
  35. Townsend AR, Skehel JJ. The influenza A virus nucleoprotein gene controls the induction of both subtype specific and cross-reactive cytotoxic T cells. J Exp Med 1984;160:552–563 [CrossRef][PubMed]
    [Google Scholar]
  36. Xu J, Zhong HA, Madrahimov A, Helikar T, Lu G. Molecular phylogeny and evolutionary dynamics of influenza A nonstructural (NS) gene. Infect Genet Evol 2014;22:192–200 [CrossRef][PubMed]
    [Google Scholar]
  37. Seidel W, Künkel F, Geisler B, Garten W, Herrmann B et al. Intraepidemic variants of influenza virus H3 hemagglutinin differing in the number of carbohydrate side chains. Arch Virol 1991;120:289–296 [CrossRef][PubMed]
    [Google Scholar]
  38. Blackburne BP, Hay AJ, Goldstein RA. Changing selective pressure during antigenic changes in human influenza H3. PLoS Pathog 2008;4:e1000058 [CrossRef][PubMed]
    [Google Scholar]
  39. Fitch WM, Leiter JM, Li XQ, Palese P. Positive Darwinian evolution in human influenza A viruses. Proc Natl Acad Sci USA 1991;88:4270–4274 [CrossRef][PubMed]
    [Google Scholar]
  40. Eshaghi A, Duvvuri VR, Li A, Patel SN, Bastien N et al. Genetic characterization of seasonal influenza A (H3N2) viruses in Ontario during 2010-2011 influenza season: high prevalence of mutations at antigenic sites. Influenza Other Respir Viruses 2014;8:250–257 [CrossRef][PubMed]
    [Google Scholar]
  41. Bedford T, Suchard MA, Lemey P, Dudas G, Gregory V et al. Integrating influenza antigenic dynamics with molecular evolution. Elife 2014;3:e01914 [CrossRef][PubMed]
    [Google Scholar]
  42. Wedde M, Biere B, Wolff T, Schweiger B. Evolution of the hemagglutinin expressed by human influenza A(H1N1)pdm09 and A(H3N2) viruses circulating between 2008–2009 and 2013–2014 in Germany. Int J Med Microbiol 2015;305:762–775 [CrossRef][PubMed]
    [Google Scholar]
  43. WHO 2017; Recommended composition of influenza virus vaccines for use in the 2017–2018 northern hemisphere influenza season. Available onlinewww.who.int/influenza/vaccines/virus/recommendations/201703_recommendation.pdf?ua=1
  44. Chen R, Holmes EC. The evolutionary dynamics of human influenza B virus. J Mol Evol 2008;66:655–663 [CrossRef][PubMed]
    [Google Scholar]
  45. Lugovtsev VY, Vodeiko GM, Strupczewski CM, Ye Z, Levandowski RA. Generation of the influenza B viruses with improved growth phenotype by substitution of specific amino acids of hemagglutinin. Virology 2007;365:315–323 [CrossRef][PubMed]
    [Google Scholar]
  46. Wang Q, Cheng F, Lu M, Tian X, Ma J. Crystal structure of unliganded influenza B virus hemagglutinin. J Virol 2008;82:3011–3020 [CrossRef][PubMed]
    [Google Scholar]
  47. Tramuto F, Orsi A, Maida CM, Costantino C, Trucchi C et al. The molecular epidemiology and evolutionary dynamics of influenza B virus in two Italian regions during 2010–2015: the experience of Sicily and Liguria. Int J Mol Sci 2016;17:549 [CrossRef][PubMed]
    [Google Scholar]
  48. Blanton L, Alabi N, Mustaquim D, Taylor C, Kniss K et al. Update: influenza activity in the United States during the 2016–17 season and composition of the 2017–18 influenza vaccine. MMWR Morb Mortal Wkly Rep 2017;66:668–676 [CrossRef][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.000668
Loading
/content/journal/jmm/10.1099/jmm.0.000668
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error