PXD018920

PXD018920 is an original dataset announced via ProteomeXchange.

Title	Influenza A hemagglutinin glycoproteomics similarity
Description	Influenza A virus (IAV) mutates rapidly, preventing a single seasonal vaccine from targeting more than one strain, and year-to-year vaccine effectiveness is low. One challenge in designing effective vaccines is that genetic mutations frequently cause amino acid variations in IAV envelope protein hemagglutinin (HA) that create new N-glycosylation sequons; resulting N-glycans cause antigenic shielding, allowing viral escape from adaptive immune responses. Vaccine candidate strain selection currently involves correlating antigenicity with HA protein sequence among circulating strains, but quantitative comparison of site-specific glycosylation information is likely to improve the ability to design vaccines with broader effectiveness against evolved strains. However, there is poor understanding of the influence of glycosylation on immunodominance, antigenicity, and immunogenicity of HA, and there are no well-tested methods for comparing glycosylation similarity among virus samples. Here, we present a method for statistically rigorous quantification of similarity between two related virus strains that considers the presence and abundance of glycopeptide glycoforms. We demonstrate the strength of our approach by determining that there was a quantifiable difference in glycosylation at the protein level between wild-type IAV HA from A/Switzerland/9715293/2013 (SWZ13) and a mutant strain of SWZ13, even though no N-glycosylation sequons were changed. We determined site-specifically that WT and mutant HA have varying similarity at the glycosylation sites of the head domain, reflecting competing pressures to evade host immune response while retaining viral fitness. To our knowledge, our results are the first to quantify changes in glycosylation state that occur in related proteins of considerable glycan heterogeneity. Our results provide a method for understanding how changes in glycosylation state are correlated with variations in protein sequence, which is necessary for improving IAV vaccine strain selection. Understanding glycosylation will be especially important as we find new expression vectors for vaccine production, as glycosylation state depends greatly on the host species.
HostingRepository	PRIDE
AnnounceDate	2020-07-03
AnnouncementXML	Submission_2020-07-03_03:35:56.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD018920
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Deborah Chang
SpeciesList	scientific name: Gallus gallus (Chicken); NCBI TaxID: 9031; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Oxidation; monohydroxylated residue; Carbamidomethyl; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-29 18:09:40	ID requested
⏵ 1	2020-07-03 03:35:57	announced

Chang D, Hackett WE, Zhong L, Wan XF, Zaia J, Measuring Site-specific Glycosylation Similarity between Influenza a Virus Variants with Statistical Certainty. Mol Cell Proteomics, 19(9):1533-1545(2020) [pubmed]

submitter keyword: influenza A, glycopeptides, LC-MS, glycosylation, similarity

Joseph Zaia
contact affiliation	Department of Biochemistry Center for Biomedical Mass Spectrometry Boston University School of Medicine
contact email	jzaia@bu.edu
lab head
Deborah Chang
contact affiliation	Boston University School of Medicine
contact email	changd@bu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD018920
     1. Label: PRIDE project
     2. Name: Influenza A hemagglutinin glycoproteomics similarity