Effect of addition of new oligosaccharide chains to the globular head of influenza A/H2N2 virus haemagglutinin on the intracellular transport and biological activities of the molecule

Tsuchiya, Emi; Sugawara, Kanetsu; Hongō, Seiji; Matsuzaki, Yoko; Muraki, Yasushi; Li, Zhu-Nan; Nakamura, Kenzo

doi:10.1099/0022-1317-83-5-1137

Cited by 59 publications

(68 citation statements)

References 19 publications

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“…In the globular head, Nlinked glycosylation sites usually overlap with antigenic sites. N-linked glycans may be involved in shielding of antigenic sites from binding by antibodies (Skehel et al, 1984;Tsuchiya et al, 2002;Das et al, 2010;Wei et al, 2010;Wanzeck et al, 2011) and major histocompatibility complex (Jackson et al, 1994), interference with proteolytic activity of HA, and recognition by collectins for neutralization (Vigerust et al, 2007). In addition, structural complexity of N-linked glycans is positively and negatively correlated with HA-receptor binding specificity and affinity, respectively (Tsuchiya et al, 2002;Wang et al, 2009;de Vries et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Positive selection for gains of N-linked glycosylation sites in hemagglutinin during evolution of H3N2 human influenza A virus

Suzuki

2011

Genes Genet. Syst.

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The number of N-linked glycosylation sites in the globular head of hemagglutinin (HA) has increased during evolution of H3N2 human influenza A virus. Here natural selection operating on the gains of N-linked glycosylation sites was examined by using the single-site analysis and the single-substitution analysis. In the single-site analysis, positive selection was not inferred at the amino acid sites where the substitutions generating N-linked glycosylation sites were observed, but was detected at antigenic sites. In contrast, in the single-substitution analysis, positive selection was detected for the amino acid substitutions generating Nlinked glycosylation sites. The single-site analysis and the single-substitution analysis appeared to be suitable for detecting recurrent and episodic natural selection, respectively. The gains of N-linked glycosylation sites were likely to be positively selected for the function of shielding antigenic sites from immune responses. At the antigenic sites, positive selection appeared to have operated not only on the radical substitution but also on the conservative substitution in terms of the charge of amino acids, suggesting that the antigenic drift is not a byproduct of the evolution of receptor binding avidity in HA of human H3N2 virus.

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Section: Introductionmentioning

confidence: 99%

Positive selection for gains of N-linked glycosylation sites in hemagglutinin during evolution of H3N2 human influenza A virus

Suzuki

2011

Genes Genet. Syst.

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“…Secondly, the positions where the amino acid changes occurred during readaptation were previously identified as those involved in the variation of virulence. This observation concerns not only the role of position 131 (Gitelman et al, 1986;Tsuchiya et al, 2002), but also the mutation T113I in the readaptants RAm55(13) and RAm55(14). In both readaptants the attenuating mutation K156N was preserved, yet the viruses regained virulence.…”

Section: Discussionmentioning

confidence: 99%

“…For example, the acquisition of glycosylation sites by escape mutants of an H2 virus is associated with decreased cell fusion and receptor-binding activity of HA (Tsuchiya et al, 2002). An H3 drift variant is reported to have a decreased capacity to reproduce in mouse lungs (Reading et al, 1997), and a change in the receptorbinding ability of HA has been described for H3 escape mutants (Daniels et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

Restoration of virulence of escape mutants of H5 and H9 influenza viruses by their readaptation to mice

Руднева

Ilyushina

Тимофеева

et al. 2005

Journal of General Virology

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Antigenic mapping of the haemagglutinin (HA) molecule of H5 and H9 influenza viruses by selecting escape mutants with monoclonal anti-HA antibodies and subjecting the selected viruses to immunological analysis and sequencing has previously been performed. The viruses used as wild-type strains were mouse-adapted variants of the original H5 and H9 isolates. Phenotypic characterization of the escape mutants revealed that the amino acid change in HA that conferred resistance to a monoclonal antibody was sometimes associated with additional effects, including decreased virulence for mice. In the present study, the low-virulence H5 and H9 escape mutants were readapted to mice. Analysis of the readapted variants revealed that the reacquisition of virulence was not necessarily achieved by reacquisition of the wild-type HA gene sequence, but was also associated either with the removal of a glycosylation site (the one acquired previously by the escape mutant) without the exact restoration of the initial wild-type amino acid sequence, or, for an H5 escape mutant that had no newly acquired glycosylation sites, with an additional amino acid change in a remote part of the HA molecule. The data suggest that such 'compensating' mutations, removing the damaging effects of antibody-selected amino acid changes, may be important in the course of influenza virus evolution.

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“…Further, the addition of increased carbohydrate onto the globular head of the HA molecule of H3N2 viruses results in decreased receptor binding but had no effect on fusion activity, suggesting no negative impact to function. Conversely, the addition of glycan to the globular head of H2N2 HA does indeed affect both receptor binding and fusion activity [45,46]. The effect of glycan addition was especially important when looking at the interaction of HA and NA by showing that a balance is needed between receptor binding activity and virus release [52].…”

Section: Orthomyxovirus and Paramyxovirusmentioning

confidence: 99%

“…Several influenza proteins have been clearly demonstrated or predicted to have carbohydrate modifications. The surface proteins hemagglutinin (HA) and neuraminidase (NA) both use glycosylation for a variety of important functions including receptor binding, infectivity, virus release, and neurovirulence [42][43][44][45][46][47][48]. HA is the major antigenic surface glycoprotein of influenza and mediates attachment and entry into target cells.…”

Section: Orthomyxovirus and Paramyxovirusmentioning

confidence: 99%

Protein glycosylation in infectious disease pathobiology and treatment

Vigerust¹

2011

Open Life Sciences

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A host of bacteria and viruses are dependent on O-linked and N-linked glycosylation to perform vital biological functions. Pathogens often have integral proteins that participate in host-cell interactions such as receptor binding and fusion with host membrane. Fusion proteins from a broad range of disparate viruses, such as paramyxovirus, HIV, ebola, and the influenza viruses share a variety of common features that are augmented by glycosylation. Each of these viruses contain multiple glycosylation sites that must be processed and modified by the host post-translational machinery to be fusogenically active. In most viruses, glycosylation plays a role in biogenesis, stability, antigenicity and infectivity. In bacteria, glycosylation events play an important role in the formation of flagellin and pili and are vitally important to adherence, attachment, infectivity and immune evasion. With the importance of glycosylation to pathogen survival, it is clear that a better understanding of the processes is needed to understand the pathogen requirement for glycosylation and to capitalize on this requirement for the development of novel therapeutics.

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Effect of addition of new oligosaccharide chains to the globular head of influenza A/H2N2 virus haemagglutinin on the intracellular transport and biological activities of the molecule

Cited by 59 publications

References 19 publications

Positive selection for gains of N-linked glycosylation sites in hemagglutinin during evolution of H3N2 human influenza A virus

Positive selection for gains of N-linked glycosylation sites in hemagglutinin during evolution of H3N2 human influenza A virus

Restoration of virulence of escape mutants of H5 and H9 influenza viruses by their readaptation to mice

Protein glycosylation in infectious disease pathobiology and treatment

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