Antibody Recognition of the Influenza Virus Neuraminidase

Air, Gillian M.; Laver, W.G.; Rg, Webster; Els, M.C.; Luo, Ming

doi:10.1101/sqb.1989.054.01.031

Cited by 11 publications

(7 citation statements)

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“…Regions A and B are important regions with frequently altered glycosylation sites. (D) A monomer of NA with the location of the enzyme active site and the seven antigenic sites surrounding the enzyme active [40], [50]. Region C is an important glycosylation region surrounding the enzyme active site.…”

Section: Resultsmentioning

confidence: 99%

Glycosylation Site Alteration in the Evolution of Influenza A (H1N1) Viruses

et al. 2011

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Influenza virus typically alters protein glycosylation in order to escape immune pressure from hosts and hence to facilitate survival in different host environments. In this study, the patterns and conservation of glycosylation sites on HA and NA of influenza A/H1N1 viruses isolated from various hosts at different time periods were systematically analyzed, by employing a new strategy combining genome-based glycosylation site prediction and 3D modeling of glycoprotein structures, for elucidation of the modes and laws of glycosylation site alteration in the evolution of influenza A/H1N1 viruses. The results showed that influenza H1N1 viruses underwent different alterations of protein glycosylation in different hosts. Two alternative modes of glycosylation site alteration were involved in the evolution of human influenza virus: One was an increase in glycosylation site numbers, which mainly occurred with high frequency in the early stages of evolution. The other was a change in the positional conversion of the glycosylation sites, which was the dominating mode with relatively low frequency in the later evolutionary stages. The mechanisms and possibly biological functions of glycosylation site alteration for the evolution of influenza A/H1N1 viruses were also discussed. Importantly, the significant role of positional alteration of glycosylation sites in the host adaptation of influenza virus was elucidated. Although the results still need to be supported by experimental data, the information here may provide some constructive suggestions for research into the glycosylation of influenza viruses as well as even the design of surveillance and the production of viral vaccines.

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Section: Resultsmentioning

confidence: 99%

Glycosylation Site Alteration in the Evolution of Influenza A (H1N1) Viruses

et al. 2011

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“…Analyses of complexes formed between antibodies and protein antigens have demonstrated interactions between 15 and 22 amino acids on both the antigen and the antibody molecule (17)(18)(19)(20)(21)(22)(23) . Nevertheless, single amino acid substitutions that induce only minor local alterations in the epitope can abolish antibody binding, and can lead to the induction of noncrossreactive antibodies (22,(24)(25)(26) . How the immune system distinguishes between distinct analogues of epitopes that display such extensive structural similarity has not yet been explained.…”

Section: Discussionmentioning

confidence: 99%

Antibodies that are specific for a single amino acid interchange in a protein epitope use structurally distinct variable regions.

Stark

Caton

1991

The Journal of Experimental Medicine

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SummaryWe have analyzed how the immune system generates antibodies that are specific for analogues of an epitope on the influenza virus hemagglutinin (HA) that differ solely by the presence of Asp or Gly at amino acid 225 . Most antibodies induced in response to HA(Asp225) use one of a few closely related variable (V) region structures that are encoded by characteristic VH/Vk gene segment combinations. Remarkably, none of these VH/Vk combinations was induced in response to HA(Gly225) . Instead of modifying the HA(Asp225)-specific V regions byjunctional variation or somatic mutation to recognize the altered epitope, new VH/Vk combinations were used. The expression of unique VH/Vk combinations appears to confer exquisite specificity to the selection of HAspecific B cells from the pre-immune repertoire.n both B and T lymphocytes, specific recognition is mediated through clonally distributed heterodimeric receptors. For each type of receptor, two polypeptide chains are generated by somatic rearrangement of separate V, J, and in the case of VH and VA D gene segments (reviewed in reference 1). Crystallographic analyses of antibody molecules have demonstrated that the regions of greatest sequence variability, called complementarity-determining regions (CDR), form loops (2, 3); for each polypeptide, CDR1 and CDR2 are encoded by the V gene segment, whereas the junctionally encoded CDR3 is somatically generated during V (D) J gene assembly (1,4,5). The spatial arrangement of the amino acid residues in these loops establishes the specificity of antibody molecules for protein molecules.Previous studies have clearly demonstrated that somatic alterations of V region sequences byjunctional variation and somatic mutation can play an important role in determining the specificity of antibody molecules (6-8) . For example, somatic alterations of antibodies that recognize the influenza virus A/PR/8/34 hemagglutinin (PR8 HA)' can influence their interaction with the HA, as measured by their ability to crossreact with mutant viruses that possess different amino acid substitutions in the antibody combining site (9-14) . Somatic alterations of V region sequences can also change the specificity of antibody molecules such that they recognize different antigens. An example of this is the somatic mutation of a phosphocholine-specific antibody to acquire specificity for DNA (15). Similarly, somatic mutation of V region se-I Abbreviations used in this paper. HA, hemagglutinin ; HAU, hemagglutinating units . quences can alter antibody specificity for analogues of the hapten arsonate (16) . However, the extent to which somatic alterations of V region sequences can give rise to antibodies that are specific for different protein antigens has been unclear. This question is of particular interest in view of the extensive interactions that take place in the combining site between antibodies and protein epitopes. Analyses of complexes formed between antibodies and protein antigens have demonstrated interactions between 15 and 22 amino acids on both ...

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“…5) and are thus potentially accessible to antibodies. Amino acid changes at positions 222, 329, and 344 (using amino acid numbering for the N1 sequence) correspond to antibody-binding determinants previously identified for N2 proteins (20,21). Three of the variant residues (222, 249, and 344) are located on the periphery of the enzyme active site, and another (329) is located on a loop more distant from the active site.…”

Section: Single Amino Acid Change Is Largely Responsible For the Antimentioning

confidence: 99%

Discordant antigenic drift of neuraminidase and hemagglutinin in H1N1 and H3N2 influenza viruses

Sandbulte

Westgeest²,

Gao³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

208

185

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Seasonal epidemics caused by influenza virus are driven by antigenic changes (drift) in viral surface glycoproteins that allow evasion from preexisting humoral immunity. Antigenic drift is a feature of not only the hemagglutinin (HA), but also of neuraminidase (NA). We have evaluated the antigenic evolution of each protein in H1N1 and H3N2 viruses used in vaccine formulations during the last 15 y by analysis of HA and NA inhibition titers and antigenic cartography. As previously shown for HA, genetic changes in NA did not always lead to an antigenic change. The noncontinuous pattern of NA drift did not correspond closely with HA drift in either subtype. Although NA drift was demonstrated using ferret sera, we show that these changes also impact recognition by NA-inhibiting antibodies in human sera. Remarkably, a single point mutation in the NA of A/Brisbane/59/2007 was primarily responsible for the lack of inhibition by polyclonal antibodies specific for earlier strains. These data underscore the importance of NA inhibition testing to define antigenic drift when there are sequence changes in NA.

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Antibody Recognition of the Influenza Virus Neuraminidase

Cited by 11 publications

References 0 publications

Glycosylation Site Alteration in the Evolution of Influenza A (H1N1) Viruses

Glycosylation Site Alteration in the Evolution of Influenza A (H1N1) Viruses

Antibodies that are specific for a single amino acid interchange in a protein epitope use structurally distinct variable regions.

Discordant antigenic drift of neuraminidase and hemagglutinin in H1N1 and H3N2 influenza viruses

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