Genetic Characterisation of the Influenza Viruses Circulating in Bulgaria During the 2019-2020 Winter Season

Overview

Journal Virus Genes

Specialties Microbiology
Molecular Biology

Date 2021 Jun 22

PMID 34156583

Citations 7

Authors

Neli Korsun

Ivelina Trifonova

Silvia Voleva

Iliyana Grigorova

Svetla Angelova

Affiliations

Soon will be listed here.

Abstract

Influenza viruses have a high potential for genetic changes. The objectives of this study were to analyse influenza virus circulation in Bulgaria during the 2019/2020 season, to perform a phylogenetic and molecular analyses of the haemagglutinin (HA) and neuraminidase (NA) sequences of representative influenza strains, and to identify amino acid substitutions compared to the current vaccine strains. Seasonal influenza viruses A(H3N2), A(H1N1)pdm09 and B/Victoria-lineage were detected using a real-time RT-PCR in 323 (23.3%), 149 (10.7%) and 138 (9.9%) out of 1387 patient samples studied, respectively. The HA genes of A(H3N2) viruses analysed belonged to clades 3C.3a (21 strains) and 3C.2a (5 strains): subclades 3C.2a1b + T131K, 3C.2a1b + T135K-B and 3C.2a1b + T135K-A. The clade 3C.3a and subclade 3C.2a1b viruses carried 5 and 14-17 substitutions in HA, as well as 3 and 9 substitutions in NA, respectively, in comparison with the A/Kansas/14/2017 vaccine virus, including some substitutions in the HA antigenic sites A, B, C and E. All 21 A(H1N1)pdm09 viruses sequenced fell into 6B.1A5A subclade. Amino acid sequence analysis revealed the presence of 7-11 substitutions in HA, compared to the A/Brisbane/02/2018 vaccine virus, three of which occurred in antigenic site Sb, along with 6-9 changes at positions in NA. All 10 B/Victoria-lineage viruses sequenced belonged to clade 1A with a triple deletion in HA1 (genetic group 1A(Δ3)B) and carried 7 and 3 substitutions in HA and NA, respectively, with respect to the B/Colorado/06/2017 vaccine virus. The results of this study confirm the rapid evolution of influenza viruses and the need for continuous antigenic and genetic surveillance.

Citing Articles

Computationally Optimized Hemagglutinin Proteins Adjuvanted with Infectimune Generate Broadly Protective Antibody Responses in Mice and Ferrets.

Allen J, Zhang X, Medina J, Thomas M, Lynch A, Nelson R Vaccines (Basel). 2025; 12(12.

PMID: 39772026 PMC: 11679666. DOI: 10.3390/vaccines12121364.

Genetic characterization of influenza B virus and oseltamivir resistance in pediatric patients with acute respiratory infections: a cross-sectional study.

Alizadeh S, Edalat F, Letafati A, Pirbonyeh N, Tabibzadeh A, Mousavizadeh L Virus Genes. 2024; 61(1):54-63.

PMID: 39499431 DOI: 10.1007/s11262-024-02119-x.

Emergence of Eurasian Avian-Like Swine Influenza A (H1N1) virus in a child in Shandong Province, China.

He Y, Song S, Wu J, Wu J, Zhang L, Sun L BMC Infect Dis. 2024; 24(1):550.

PMID: 38824508 PMC: 11143696. DOI: 10.1186/s12879-024-09441-7.

mRNA vaccines encoding computationally optimized hemagglutinin elicit protective antibodies against future antigenically drifted H1N1 and H3N2 influenza viruses isolated between 2018-2020.

Allen J, Ross T Front Immunol. 2024; 15:1334670.

PMID: 38533508 PMC: 10963417. DOI: 10.3389/fimmu.2024.1334670.

Genome characterization of influenza A and B viruses in New South Wales, Australia, in 2019: A retrospective study using high-throughput whole genome sequencing.

Wang X, Kim K, Walker G, Stelzer-Braid S, Scotch M, Rawlinson W Influenza Other Respir Viruses. 2024; 18(1):e13252.

PMID: 38288510 PMC: 10824601. DOI: 10.1111/irv.13252.

References

Korsun N, Angelova S, Trifonova I, Tzotcheva I, Mileva S, Voleva S . Predominance of influenza A(H3N2) viruses during the 2016/2017 season in Bulgaria. J Med Microbiol. 2018; 67(2):228-239. DOI: 10.1099/jmm.0.000668. View

Korsun N, Angelova S, Gregory V, Daniels R, Georgieva I, McCauley J . Antigenic and genetic characterization of influenza viruses circulating in Bulgaria during the 2015/2016 season. Infect Genet Evol. 2017; 49:241-250. PMC: 5348111. DOI: 10.1016/j.meegid.2017.01.027. View

Webster R, Laver W, Air G, Schild G . Molecular mechanisms of variation in influenza viruses. Nature. 1982; 296(5853):115-21. DOI: 10.1038/296115a0. View

Broberg E, Snacken R, Adlhoch C, Beaute J, Galinska M, Pereyaslov D . Start of the 2014/15 influenza season in Europe: drifted influenza A(H3N2) viruses circulate as dominant subtype. Euro Surveill. 2015; 20(4). DOI: 10.2807/1560-7917.es2015.20.4.21023. View

Krystal M, Young J, Palese P, Wilson I, Skehel J, Wiley D . Sequential mutations in hemagglutinins of influenza B virus isolates: definition of antigenic domains. Proc Natl Acad Sci U S A. 1983; 80(14):4527-31. PMC: 384072. DOI: 10.1073/pnas.80.14.4527. View

Bedford T, Suchard M, Lemey P, Dudas G, Gregory V, Hay A . Integrating influenza antigenic dynamics with molecular evolution. Elife. 2014; 3:e01914. PMC: 3909918. DOI: 10.7554/eLife.01914. View

Tramuto F, Orsi A, Maida C, Costantino C, Trucchi C, Alicino C . 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(4):549. PMC: 4849005. DOI: 10.3390/ijms17040549. View

Zost S, Parkhouse K, Gumina M, Kim K, Diaz Perez S, Wilson P . Contemporary H3N2 influenza viruses have a glycosylation site that alters binding of antibodies elicited by egg-adapted vaccine strains. Proc Natl Acad Sci U S A. 2017; 114(47):12578-12583. PMC: 5703309. DOI: 10.1073/pnas.1712377114. View

Blanton L, Alabi N, Mustaquim D, Taylor C, Kniss K, Kramer N . 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(25):668-676. PMC: 5687497. DOI: 10.15585/mmwr.mm6625a3. View

10.

Rambaut A, Pybus O, Nelson M, Viboud C, Taubenberger J, Holmes E . The genomic and epidemiological dynamics of human influenza A virus. Nature. 2008; 453(7195):615-9. PMC: 2441973. DOI: 10.1038/nature06945. View

11.

Honemann M, Martin D, Pietsch C, Maier M, Bergs S, Bieck E . Influenza B virus infections in Western Saxony, Germany in three consecutive seasons between 2015 and 2018: Analysis of molecular and clinical features. Vaccine. 2019; 37(43):6550-6557. PMC: 7115636. DOI: 10.1016/j.vaccine.2019.08.027. View

12.

Wilson J, Guo Z, Tzeng W, Garten R, Xiyan X, Blanchard E . Diverse antigenic site targeting of influenza hemagglutinin in the murine antibody recall response to A(H1N1)pdm09 virus. Virology. 2015; 485:252-62. PMC: 5737639. DOI: 10.1016/j.virol.2015.08.004. View

13.

Koel B, Burke D, Bestebroer T, van der Vliet S, Zondag G, Vervaet G . Substitutions near the receptor binding site determine major antigenic change during influenza virus evolution. Science. 2013; 342(6161):976-9. DOI: 10.1126/science.1244730. View

14.

Wiley D, Wilson I, Skehel J . Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation. Nature. 1981; 289(5796):373-8. DOI: 10.1038/289373a0. View

15.

Wang Q, Cheng F, Lu M, Tian X, Ma J . Crystal structure of unliganded influenza B virus hemagglutinin. J Virol. 2008; 82(6):3011-20. PMC: 2259021. DOI: 10.1128/JVI.02477-07. View

16.

Allen J, Ross T . H3N2 influenza viruses in humans: Viral mechanisms, evolution, and evaluation. Hum Vaccin Immunother. 2018; 14(8):1840-1847. PMC: 6149781. DOI: 10.1080/21645515.2018.1462639. View

17.

Korsun N, Daniels R, Angelova S, Ermetal B, Grigorova I, Voleva S . Genetic diversity of influenza A viruses circulating in Bulgaria during the 2018-2019 winter season. J Med Microbiol. 2020; 69(7):986-998. PMC: 7481746. DOI: 10.1099/jmm.0.001198. View

18.

Shu Y, McCauley J . GISAID: Global initiative on sharing all influenza data - from vision to reality. Euro Surveill. 2017; 22(13). PMC: 5388101. DOI: 10.2807/1560-7917.ES.2017.22.13.30494. View

19.

Andres C, Peremiquel-Trillas P, Gimferrer L, Pinana M, Codina M, Rodrigo-Pendas J . Molecular influenza surveillance at a tertiary university hospital during four consecutive seasons (2012-2016) in Catalonia, Spain. Vaccine. 2019; 37(18):2470-2476. PMC: 7173002. DOI: 10.1016/j.vaccine.2019.03.046. View

20.

Lugovtsev V, Vodeiko G, Strupczewski C, Ye Z, Levandowski R . Generation of the influenza B viruses with improved growth phenotype by substitution of specific amino acids of hemagglutinin. Virology. 2007; 365(2):315-23. DOI: 10.1016/j.virol.2007.04.006. View