Escape mutants of pandemic influenza A/H1N1 2009 virus: Variations in antigenic specificity and receptor affinity of the hemagglutinin

Руднева, И. А.; Ignatieva, Anna V.; Тимофеева, Т. А.; Шилов, А. А.; Кущ, А А; Масалова, О. В.; Климова, Р. Р.; Bovin, Nicolai V.; Mochalova, L. V.; Каверин, Н. В.

doi:10.1016/j.virusres.2012.03.003

Cited by 43 publications

(52 citation statements)

References 38 publications

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“…However, it should be noted that it is possible that other amino acid changes outside the 151-159 loop, that were not included in this study, can result in phenotypic changes (42). Our results are in agreement with previous studies that reported mouse or human monoclonal antibodies (36,37) or antibodies in ferret antisera (38) that target the 151-159 loop. We show here that several substitutions in or affecting the 151-159 loop caused antigenic escape while retaining replicative fitness.…”

Section: Discussionsupporting

confidence: 92%

“…The observation that these substitutions changed the antigenic properties of an A(H1N1)pdm09 virus is also in agreement with previous studies that reported escape of A(H1N1)pdm09 virus from monoclonal antibodies (36,37) and from polyclonal antibody responses in ferrets (35,38,39).…”

Section: Discussionsupporting

confidence: 92%

“…Two additional substitutions at this position, 156NK and 156NE, were previously reported to allow escape of antibody neutralization of A(H1N1)pdm09 virus (37,38). Interestingly, the large changes in biophysical properties of the substituted amino acids introduced by 156ND or 156NY (charge and volume differences, respectively) had an antigenic effect similar to that of the small difference in biophysical properties introduced by 156NS.…”

Section: Discussionmentioning

confidence: 82%

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Identification of Amino Acid Substitutions Supporting Antigenic Change of Influenza A(H1N1)pdm09 Viruses

Koel

Mögling

Chutinimitkul

et al. 2015

J Virol

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The majority of currently circulating influenza A(H1N1) viruses are antigenically similar to the virus that caused the 2009 influenza pandemic. However, antigenic variants are expected to emerge as population immunity increases. Amino acid substitutions in the hemagglutinin protein can result in escape from neutralizing antibodies, affect viral fitness, and change receptor preference. In this study, we constructed mutants with substitutions in the hemagglutinin of A/Netherlands/602/09 in an attenuated backbone to explore amino acid changes that may contribute to emergence of antigenic variants in the human population. Our analysis revealed that single substitutions affecting the loop that consists of amino acid positions 151 to 159 located adjacent to the receptor binding site caused escape from ferret and human antibodies elicited after primary A(H1N1)pdm09 virus infection. The majority of these substitutions resulted in similar or increased replication efficiency in vitro compared to that of the virus carrying the wild-type hemagglutinin and did not result in a change of receptor preference. However, none of the substitutions was sufficient for escape from the antibodies in sera from individuals that experienced both seasonal and pandemic A(H1N1) virus infections. These results suggest that antibodies directed against epitopes on seasonal A(H1N1) viruses contribute to neutralization of A(H1N1)pdm09 antigenic variants, thereby limiting the number of possible substitutions that could lead to escape from population immunity. A prerequisite for the influenza virus to infect the host cell is the binding of the hemagglutinin (HA) surface protein to sialylated glycan receptors on the host cell through its receptor binding site (RBS). HA is the main target of neutralizing antibodies and is therefore a critical component of influenza vaccines (5). Influenza viruses continually escape antibody-mediated neutralization by Citation Koel BF, Mögling R, Chutinimitkul S, Fraaij PL, Burke DF, van der Vliet S, de Wit E, Bestebroer TM, Rimmelzwaan GF, Osterhaus ADME, Smith DJ, Fouchier RAM, de Graaf M. 2015. Identification of amino acid substitutions supporting antigenic change of influenza A(H1N1)pdm09 viruses.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 82%

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Identification of Amino Acid Substitutions Supporting Antigenic Change of Influenza A(H1N1)pdm09 Viruses

Koel

Mögling

Chutinimitkul

et al. 2015

J Virol

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“…Vac-cines work by primarily eliciting neutralizing antibodies that target the head region of HA and sterically inhibiting the HAglycan interaction (9,10). However, the virus can easily mutate to escape from neutralizing antibodies while still binding to the host-glycan receptors (9,11).…”

Section: Lstc-bearing Decoy Liposomes Form Multivalent Polymer-like mentioning

confidence: 99%

Sialylneolacto-N-tetraose c (LSTc)-bearing Liposomal Decoys Capture Influenza A Virus

Hendricks

Weirich

Viswanathan

et al. 2013

Journal of Biological Chemistry

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“…To take precautions against antigenic drift of the pdm09 virus in the near future, it is important to determine the precise antigenic structure of pdm09 HA. In response to the 2009 pandemic, several groups elucidated the antigenic region of pdm09 HA using HA MAbs; however, a systemic analysis of the epitopes has not previously been performed (13)(14)(15)(16).…”

mentioning

confidence: 99%

Epitope Mapping of the Hemagglutinin Molecule of A/(H1N1)pdm09 Influenza Virus by Using Monoclonal Antibody Escape Mutants

Matsuzaki

Sugawara

Nakauchi

et al. 2014

J Virol

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We determined the antigenic structure of pandemic influenza A(H1N1)pdm09 virus hemagglutinin (HA) using 599 escape mutants that were selected using 16 anti-HA monoclonal antibodies ( IMPORTANCEThe first influenza pandemic of the 21st century occurred in 2009 with the emergence of a novel virus originating with swine influenza, A(H1N1)pdm09. Although HA of A(H1N1)pdm09 has a common origin (1918 H1N1) with seasonal H1N1, the antigenic divergence of HA between the seasonal H1N1 and A(H1N1)pdm09 viruses gave rise to the influenza pandemic in 2009. To take precautions against the antigenic drift of the A(H1N1)pdm09 virus in the near future, it is important to identify its precise antigenic structure. To obtain various mutants that are not neutralized by MAbs, it is important to neutralize several plaque-cloned parent viruses rather than only a single parent virus. We characterized 599 escape mutants that were obtained by neutralizing four parent viruses of A(H1N1)pdm09 in the presence of 16 MAbs. Consequently, we were able to determine the details of the antigenic structure of HA, including a novel epitope.

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Escape mutants of pandemic influenza A/H1N1 2009 virus: Variations in antigenic specificity and receptor affinity of the hemagglutinin

Cited by 43 publications

References 38 publications

Identification of Amino Acid Substitutions Supporting Antigenic Change of Influenza A(H1N1)pdm09 Viruses

Identification of Amino Acid Substitutions Supporting Antigenic Change of Influenza A(H1N1)pdm09 Viruses

Sialylneolacto-N-tetraose c (LSTc)-bearing Liposomal Decoys Capture Influenza A Virus

Epitope Mapping of the Hemagglutinin Molecule of A/(H1N1)pdm09 Influenza Virus by Using Monoclonal Antibody Escape Mutants

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