scholarly journals Heterosubtypic antibody recognition of the influenza virus hemagglutinin receptor binding site enhanced by avidity

2012 ◽  
Vol 109 (42) ◽  
pp. 17040-17045 ◽  
Author(s):  
P. S. Lee ◽  
R. Yoshida ◽  
D. C. Ekiert ◽  
N. Sakai ◽  
Y. Suzuki ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Binding Site ◽  
Receptor Binding ◽  
Receptor Binding Site ◽  
Antibody Recognition ◽  
Influenza Virus Hemagglutinin

scholarly journals Infectivity Studies of Influenza Virus Hemagglutinin Receptor Binding Site Mutants in Mice

2008 ◽  
Vol 82 (10) ◽  
pp. 5079-5083 ◽  
Author(s):  
Jeffrey Meisner ◽  
Kristy J. Szretter ◽  
Konrad C. Bradley ◽  
William A. Langley ◽  
Zhu-Nan Li ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Binding Site ◽  
Receptor Binding ◽  
Mdck Cells ◽  
Receptor Binding Site ◽  
Binding Characteristics ◽  
Influenza Virus Hemagglutinin ◽  
Fold Reduction ◽  
Chicken Eggs ◽  
Embryonated Chicken

ABSTRACT The replicative properties of influenza virus hemagglutinin (HA) mutants with altered receptor binding characteristics were analyzed following intranasal inoculation of mice. Among the mutants examined was a virus containing a Y98F substitution at a conserved position in the receptor binding site that leads to a 20-fold reduction in binding. This mutant can replicate as well as wild-type (WT) virus in MDCK cells and in embryonated chicken eggs but is highly attenuated in mice, exhibiting titers in lungs more than 1,000-fold lower than those of the WT. The capacity of the Y98F mutant to induce antibody responses and the structural locations of HA reversion mutations are examined.

scholarly journals Identification of antibodies targeting the H3N2 hemagglutinin receptor binding site following vaccination of humans

2019 ◽  
Author(s):  
Seth J. Zost ◽  
Juhye Lee ◽  
Megan E. Gumina ◽  
Kaela Parkhouse ◽  
Carole Henry ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Monoclonal Antibodies ◽  
Binding Site ◽  
Receptor Binding ◽  
Receptor Binding Site ◽  
Antigenic Sites ◽  
Influenza Virus Hemagglutinin ◽  
Ha Protein

SUMMARYAntibodies targeting the receptor binding site (RBS) of the influenza virus hemagglutinin (HA) protein are usually not broadly-reactive because their footprints are typically large and extend to nearby variable HA residues. Here, we identified several human H3N2 HA RBS-targeting monoclonal antibodies (mAbs) that were sensitive to substitutions in conventional antigenic sites and were not broadly-reactive. However, we also identified one H3N2 HA RBS-targeting mAb that was exceptionally broadly reactive despite being sensitive to substitutions in residues outside of the RBS. We determined that similar antibodies are present at measurable levels in the sera of some individuals but that they are inefficiently elicited by conventional vaccines. Our data indicate that some HA RBS-targeting antibodies can be surprisingly effective against variable viral strains even if they are somewhat sensitive to substitutions in HA residues adjacent to the RBS.

scholarly journals Tight Binding of Influenza Virus Hemagglutinin to Its Receptor Interferes with Fusion Pore Dilation

2002 ◽  
Vol 76 (24) ◽  
pp. 12405-12413 ◽  
Author(s):  
Masanobu Ohuchi ◽  
Reiko Ohuchi ◽  
Tatsuya Sakai ◽  
Akira Matsumoto
Keyword(s):  
Influenza Virus ◽  
Binding Site ◽  
Cell Fusion ◽  
Receptor Binding ◽  
Deletion Mutant ◽  
Binding Activity ◽  
Side Chains ◽  
Fusion Activity ◽  
Receptor Binding Site ◽  
Fusion Pores

ABSTRACT Deletion of oligosaccharide side chains near the receptor binding site of influenza virus A/USSR/90/77 (H1N1) hemagglutinin (HA) enhanced the binding of HA to erythrocyte receptors, as was also observed with A/FPV/Rostock/34 (H7N1). Correlated with the enhancement of binding activity, the cell fusion activity of HA was reduced. A mutant HA in which three oligosaccharide side chains were deleted showed the highest level of binding and the lowest level of fusion among the HAs tested. The cell fusion activity of the oligosaccharide deletion mutant of HA, however, was drastically elevated when the binding activity was reduced by deletion of four amino acids adjacent to the receptor binding site. Thus, a reciprocal relationship was observed between the receptor binding and the cell fusion activities of H1/USSR HA. No difference was observed, however, in lipid mixing activity, so-called hemifusion, between wild-type (WT) and oligosaccharide deletion mutant HAs. Soluble dye transfer testing showed that even the HA with the lowest cell fusion activity was able to form fusion pores through which a small molecule such as calcein could pass. However, electron microscopic studies revealed that a large molecule such as hemoglobin hardly passed through the fusion pores formed by the mutant HA, whereas hemoglobin did efficiently pass through those formed by the WT HA. These results suggested that interference in the process of dilation of fusion pores occurs when the binding of HA to the receptor is too tight. Since the viral nucleocapsid is far larger than hemoglobin, appropriate receptor binding affinity is important for virus entry.

scholarly journals CryoEM Structure of an Influenza Virus Receptor-Binding Site Antibody–Antigen Interface

2017 ◽  
Vol 429 (12) ◽  
pp. 1829-1839 ◽  
Author(s):  
Yuhang Liu ◽  
Junhua Pan ◽  
Simon Jenni ◽  
Donald D. Raymond ◽  
Tim Caradonna ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Binding Site ◽  
Receptor Binding ◽  
Receptor Binding Site ◽  
Virus Receptor

scholarly journals N-Linked Glycans and K147 Residue on Hemagglutinin Synergize To Elicit Broadly Reactive H1N1 Influenza Virus Antibodies

2019 ◽  
Vol 94 (6) ◽  
Author(s):  
Ying Huang ◽  
Simon O. Owino ◽  
Corey J. Crevar ◽  
Donald M. Carter ◽  
Ted M. Ross
Keyword(s):  
Amino Acids ◽  
Influenza Virus ◽  
Binding Site ◽  
Receptor Binding ◽  
Hemagglutination Inhibition ◽  
Vaccine Development ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Wild Type ◽  
Receptor Binding Site

ABSTRACT Vaccination is the most effective way to prevent influenza virus infections. However, the diversity of antigenically distinct isolates is a challenge for vaccine development. In order to overcome the antigenic variability and improve the protective efficacy of influenza vaccines, our research group has pioneered the development of computationally optimized broadly reactive antigens (COBRA) for hemagglutinin (HA). Two candidate COBRA HA vaccines, P1 and X6, elicited antibodies with differential patterns of hemagglutination inhibition (HAI) activity against a panel of H1N1 influenza viruses. In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile. Mice were vaccinated with virus-like particles (VLPs) expressing one of the 12 modified HA antigens (designated V1 to V12), COBRA HA antigens, or wild-type HA antigens. The elicited antisera was assessed for hemagglutination inhibition activity against a panel of historical seasonal-like and pandemic-like H1N1 influenza viruses. Primarily, the pattern of glycosylation sites and residues in the Sa antigenic region, around the receptor binding site (RBS), served as signatures for the elicitation of broadly reactive antibodies by these HA immunogens. Mice were vaccinated with VLPs expressing HA antigens that lacked a glycosylation site at residue 144 and a deleted lysine at position 147 residue were more effective at protecting against morbidity and mortality following infection with pandemic-like and seasonal-like H1N1 influenza viruses. IMPORTANCE There is a great need to develop broadly reactive or universal vaccines against influenza viruses. Advanced, next-generation hemagglutinin (HA) head-based vaccines that elicit protective antibodies against H1N1 influenza viruses have been developed. This study focused on understanding the specific amino acids around the receptor binding site (RBS) that were important in elicitation of these broadly reactive antibodies. Specific glycan sites and amino acids located at the tip of the HA molecule enhanced the elicitation of these broadly reactive antibodies. A better understanding of the HA structures around the RBS will lead to more effective HA immunogens.

scholarly journals A recurring motif for antibody recognition of the receptor-binding site of influenza hemagglutinin

2013 ◽  
Vol 20 (3) ◽  
pp. 363-370 ◽  
Author(s):  
Rui Xu ◽  
Jens C Krause ◽  
Ryan McBride ◽  
James C Paulson ◽  
James E Crowe ◽  
...  
Keyword(s):  
Binding Site ◽  
Receptor Binding ◽  
Receptor Binding Site ◽  
Antibody Recognition ◽  
Influenza Hemagglutinin

scholarly journals Inactivation of influenza virus haemagglutinin by chlorine dioxide: oxidation of the conserved tryptophan 153 residue in the receptor-binding site

2012 ◽  
Vol 93 (12) ◽  
pp. 2558-2563 ◽  
Author(s):  
Norio Ogata
Keyword(s):  
Influenza Virus ◽  
Binding Site ◽  
Receptor Binding ◽  
Chlorine Dioxide ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Life Time ◽  
Tryptophan Residue ◽  
Dependent Manner ◽  
Receptor Binding Site

Airborne influenza virus infection of mice can be prevented by gaseous chlorine dioxide (ClO2). This study demonstrated that ClO2 abolished the function of the haemagglutinin (HA) of influenza A virus (H1N1) in a concentration-, time- and temperature-dependent manner. The IC50 during a 2 min reaction with ClO2 at 25 °C was 13.7 µM, and the half-life time of HA with 100 µM ClO2 at 25 °C was 19.5 s. Peptides generated from a tryptic digest of ClO2-treated virus were analysed by mass spectrometry. An HA fragment, 150NLLWLTGK157 was identified in which the tryptophan residue (W153) was 32 mass units greater than expected. The W153 residue of this peptide, which is derived from the central region of the receptor-binding site of HA, is highly conserved. It was shown that W153 was oxidized to N-formylkynurenine in ClO2-treated virus. It was concluded that the inactivation of influenza virus by ClO2 is caused by oxidation of W153 in HA, thereby abolishing its receptor-binding ability.

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