Minor Changes in the Hemagglutinin of Influenza A(H1N1)2009 Virus Alter Its Antigenic Properties

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2011 Oct 25

PMID 22022458

Citations 41

Authors

Mari Strengell

Niina Ikonen

Thedi Ziegler

Ilkka Julkunen

Affiliations

Soon will be listed here.

Abstract

Background: The influenza A(H1N1)2009 virus has been the dominant type of influenza A virus in Finland during the 2009-2010 and 2010-2011 epidemic seasons. We analyzed the antigenic characteristics of several influenza A(H1N1)2009 viruses isolated during the two influenza seasons by analyzing the amino acid sequences of the hemagglutinin (HA), modeling the amino acid changes in the HA structure and measuring antibody responses induced by natural infection or influenza vaccination.

Methods/results: Based on the HA sequences of influenza A(H1N1)2009 viruses we selected 13 different strains for antigenic characterization. The analysis included the vaccine virus, A/California/07/2009 and multiple California-like isolates from 2009-2010 and 2010-2011 epidemic seasons. These viruses had two to five amino acid changes in their HA1 molecule. The mutation(s) were located in antigenic sites Sa, Ca1, Ca2 and Cb region. Analysis of the antibody levels by hemagglutination inhibition test (HI) indicated that vaccinated individuals and people who had experienced a natural influenza A(H1N1)2009 virus infection showed good immune responses against the vaccine virus and most of the wild-type viruses. However, one to two amino acid changes in the antigenic site Sa dramatically affected the ability of antibodies to recognize these viruses. In contrast, the tested viruses were indistinguishable in regard to antibody recognition by the sera from elderly individuals who had been exposed to the Spanish influenza or its descendant viruses during the early 20(th) century.

Conclusions: According to our results, one to two amino acid changes (N125D and/or N156K) in the major antigenic sites of the hemagglutinin of influenza A(H1N1)2009 virus may lead to significant reduction in the ability of patient and vaccine sera to recognize A(H1N1)2009 viruses.

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References

Xu W, Han L, Lin Z . Screening of random peptide library of hemagglutinin from pandemic 2009 A(H1N1) influenza virus reveals unexpected antigenically important regions. PLoS One. 2011; 6(3):e18016. PMC: 3060926. DOI: 10.1371/journal.pone.0018016. View

Dawood F, Jain S, Finelli L, Shaw M, Lindstrom S, Garten R . Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med. 2009; 360(25):2605-15. DOI: 10.1056/NEJMoa0903810. View

Miller E, Hoschler K, Hardelid P, Stanford E, Andrews N, Zambon M . Incidence of 2009 pandemic influenza A H1N1 infection in England: a cross-sectional serological study. Lancet. 2010; 375(9720):1100-8. DOI: 10.1016/S0140-6736(09)62126-7. View

Saitou N, Nei M . The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol. 1987; 4(4):406-25. DOI: 10.1093/oxfordjournals.molbev.a040454. View

Sui J, Hwang W, Perez S, Wei G, Aird D, Chen L . Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nat Struct Mol Biol. 2009; 16(3):265-73. PMC: 2692245. DOI: 10.1038/nsmb.1566. View

Ye J, Sorrell E, Cai Y, Shao H, Xu K, Pena L . Variations in the hemagglutinin of the 2009 H1N1 pandemic virus: potential for strains with altered virulence phenotype?. PLoS Pathog. 2010; 6(10):e1001145. PMC: 2954835. DOI: 10.1371/journal.ppat.1001145. View

Garten R, Davis C, Russell C, Shu B, Lindstrom S, Balish A . Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science. 2009; 325(5937):197-201. PMC: 3250984. DOI: 10.1126/science.1176225. View

Kilander A, Rykkvin R, Dudman S, Hungnes O . Observed association between the HA1 mutation D222G in the 2009 pandemic influenza A(H1N1) virus and severe clinical outcome, Norway 2009-2010. Euro Surveill. 2010; 15(9). DOI: 10.2807/ese.15.09.19498-en. View

Corti D, Suguitan Jr A, Pinna D, Silacci C, Fernandez-Rodriguez B, Vanzetta F . Heterosubtypic neutralizing antibodies are produced by individuals immunized with a seasonal influenza vaccine. J Clin Invest. 2010; 120(5):1663-73. PMC: 2860935. DOI: 10.1172/JCI41902. View

10.

Kaverin N, Rudneva I, Govorkova E, Timofeeva T, Shilov A, Kochergin-Nikitsky K . Epitope mapping of the hemagglutinin molecule of a highly pathogenic H5N1 influenza virus by using monoclonal antibodies. J Virol. 2007; 81(23):12911-7. PMC: 2169086. DOI: 10.1128/JVI.01522-07. View

11.

Winter G, Fields S, Brownlee G . Nucleotide sequence of the haemagglutinin gene of a human influenza virus H1 subtype. Nature. 1981; 292(5818):72-5. DOI: 10.1038/292072a0. View

12.

Ikonen N, Haanpaa M, Ronkko E, Lyytikainen O, Kuusi M, Ruutu P . Genetic diversity of the 2009 pandemic influenza A(H1N1) viruses in Finland. PLoS One. 2010; 5(10):e13329. PMC: 2958116. DOI: 10.1371/journal.pone.0013329. View

13.

Smith G, Vijaykrishna D, Bahl J, Lycett S, Worobey M, Pybus O . Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic. Nature. 2009; 459(7250):1122-5. DOI: 10.1038/nature08182. View

14.

Tamura K, Nei M, Kumar S . Prospects for inferring very large phylogenies by using the neighbor-joining method. Proc Natl Acad Sci U S A. 2004; 101(30):11030-5. PMC: 491989. DOI: 10.1073/pnas.0404206101. View

15.

Maurer-Stroh S, Lee R, Eisenhaber F, Cui L, Phuah S, Lin R . A new common mutation in the hemagglutinin of the 2009 (H1N1) influenza A virus. PLoS Curr. 2010; 2:RRN1162. PMC: 2880458. DOI: 10.1371/currents.rrn1162. View

16.

Itoh Y, Shinya K, Kiso M, Watanabe T, Sakoda Y, Hatta M . In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. Nature. 2009; 460(7258):1021-5. PMC: 2748827. DOI: 10.1038/nature08260. View

17.

Osterlund P, Pirhonen J, Ikonen N, Ronkko E, Strengell M, Makela S . Pandemic H1N1 2009 influenza A virus induces weak cytokine responses in human macrophages and dendritic cells and is highly sensitive to the antiviral actions of interferons. J Virol. 2009; 84(3):1414-22. PMC: 2812319. DOI: 10.1128/JVI.01619-09. View

18.

Ikonen N, Strengell M, Kinnunen L, Osterlund P, Pirhonen J, Broman M . High frequency of cross-reacting antibodies against 2009 pandemic influenza A(H1N1) virus among the elderly in Finland. Euro Surveill. 2010; 15(5). View

19.

Hancock K, Veguilla V, Lu X, Zhong W, Butler E, Sun H . Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus. N Engl J Med. 2009; 361(20):1945-52. DOI: 10.1056/NEJMoa0906453. View

20.

Sayle R . RASMOL: biomolecular graphics for all. Trends Biochem Sci. 1995; 20(9):374. DOI: 10.1016/s0968-0004(00)89080-5. View