tetano
Editor, Senior Moderator
Mol Cell Proteomics. 2019 Oct 11. pii: mcp.R119.001491. doi: 10.1074/mcp.R119.001491. [Epub ahead of print] [h=1]Why glycosylation matters in building a better flu vaccine.[/h]
Chang D[SUP]1[/SUP], Zaia J[SUP]2[/SUP].
[h=3]Author information[/h] 1 Boston University, United States. 2 Boston University School of Medicine, United States jzaia@bu.edu.
[h=3]Abstract[/h] Low vaccine efficacy against seasonal influenza A virus (IAV) stems from the ability of the virus to evade existing immunity while maintaining fitness. While most potent neutralizing antibodies bind antigenic sites on the globular head domain of the IAV envelope glycoprotein hemagglutinin (HA), the error-prone IAV polymerase enables rapid evolution of key antigenic sites, resulting in immune escape. Significantly, the appearance of new N-glycosylation consensus sequences (sequons, NXT/NXS, rarely NXC) on the HA globular domain occurs among the more prevalent mutations as an IAV strain undergoes antigenic drift. The appearance of new glycosylation shields underlying amino acid residues from antibody contact, tunes receptor specificity, and balances receptor avidity with virion escape, all of which help maintain viral propagation through seasonal mutations. The World Health Organization selects seasonal vaccine strains based on information from surveillance, laboratory, and clinical observations. While the genetic sequences are known, mature glycosylated structures of circulating strains are not defined. In this review, we summarize mass spectrometric methods for quantifying site-specific glycosylation in IAV strains, and compare the evolution of IAV glycosylation to that of human immunodeficiency virus. We argue that the determination of site-specific glycosylation of IAV glycoproteins would enable development of vaccines that take advantage of glycosylation-dependent mechanisms whereby virus glycoproteins are processed by antigen presenting cells.
Published under license by The American Society for Biochemistry and Molecular Biology, Inc.
[h=4]KEYWORDS:[/h] Clinical proteomics; Glycoprotein Structure*; Glycoproteins*; Glycoproteomics; Viruses; influenza A virus
PMID: 31604803 DOI: 10.1074/mcp.R119.001491
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Chang D[SUP]1[/SUP], Zaia J[SUP]2[/SUP].
[h=3]Author information[/h] 1 Boston University, United States. 2 Boston University School of Medicine, United States jzaia@bu.edu.
[h=3]Abstract[/h] Low vaccine efficacy against seasonal influenza A virus (IAV) stems from the ability of the virus to evade existing immunity while maintaining fitness. While most potent neutralizing antibodies bind antigenic sites on the globular head domain of the IAV envelope glycoprotein hemagglutinin (HA), the error-prone IAV polymerase enables rapid evolution of key antigenic sites, resulting in immune escape. Significantly, the appearance of new N-glycosylation consensus sequences (sequons, NXT/NXS, rarely NXC) on the HA globular domain occurs among the more prevalent mutations as an IAV strain undergoes antigenic drift. The appearance of new glycosylation shields underlying amino acid residues from antibody contact, tunes receptor specificity, and balances receptor avidity with virion escape, all of which help maintain viral propagation through seasonal mutations. The World Health Organization selects seasonal vaccine strains based on information from surveillance, laboratory, and clinical observations. While the genetic sequences are known, mature glycosylated structures of circulating strains are not defined. In this review, we summarize mass spectrometric methods for quantifying site-specific glycosylation in IAV strains, and compare the evolution of IAV glycosylation to that of human immunodeficiency virus. We argue that the determination of site-specific glycosylation of IAV glycoproteins would enable development of vaccines that take advantage of glycosylation-dependent mechanisms whereby virus glycoproteins are processed by antigen presenting cells.
Published under license by The American Society for Biochemistry and Molecular Biology, Inc.
[h=4]KEYWORDS:[/h] Clinical proteomics; Glycoprotein Structure*; Glycoproteins*; Glycoproteomics; Viruses; influenza A virus
PMID: 31604803 DOI: 10.1074/mcp.R119.001491
Free full text