The Role of Conserved N-Linked Glycans on Ebola Virus Glycoprotein 2

Nicholas J Lennemann; Madeline Walkner; Abigail R Berkebile; Neil Patel; Wendy Maury

doi:10.1093/infdis/jiv201

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The Role of Conserved N-Linked Glycans on Ebola Virus Glycoprotein 2

Journal article

Open access

Peer reviewed

The Role of Conserved N-Linked Glycans on Ebola Virus Glycoprotein 2

Nicholas J Lennemann, Madeline Walkner, Abigail R Berkebile, Neil Patel and Wendy Maury

The Journal of infectious diseases, Vol.212 Suppl 2(suppl 2), pp.S204-S209

10/01/2015

DOI: 10.1093/infdis/jiv201

PMCID: PMC4564545

PMID: 26038399

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Abstract

N-linked glycosylation is a common posttranslational modification found on viral glycoproteins (GPs) and involved in promoting expression, cellular attachment, protection from proteases, and antibody evasion. The GP subunit GP2 of filoviruses contains 2 completely conserved N-linked glycosylation sites (NGSs) at N563 and N618, suggesting that they have been maintained through selective pressures. We assessed mutants lacking these glycans for expression and function to understand the role of these sites during Ebola virus entry. Elimination of either GP2 glycan individually had a modest effect on GP expression and no impact on antibody neutralization of vesicular stomatitis virus pseudotyped with Ebola virus GP. However, loss of the N563 glycan enhanced entry by 2-fold and eliminated GP detection by a well-characterized monoclonal antibody KZ52. Loss of both sites dramatically decreased GP expression and abolished entry. Surprisingly, a GP that retained a single NGS at N563, eliminating the remaining 16 NGSs from GP1 and GP2, had detectable expression, a modest increase in entry, and pronounced sensitivity to antibody neutralization. Our findings support the importance of the GP2 glycans in GP expression/structure, transduction efficiency, and antibody neutralization, particularly when N-linked glycans are also removed from GP1.

Cell Line

Conserved Sequence - genetics

Viral Envelope Proteins - genetics

Humans

Polysaccharides - genetics

Cercopithecus aethiops

Vesiculovirus - immunology

Ebolavirus - pathogenicity

Ebolavirus - genetics

Mutation - genetics

Ebolavirus - immunology

Virus Internalization

Antibodies, Neutralizing - immunology

Animals

Hemorrhagic Fever, Ebola - virology

HEK293 Cells

Hemorrhagic Fever, Ebola - immunology

Vero Cells

Antibodies, Monoclonal - immunology

Details

Title: Subtitle: The Role of Conserved N-Linked Glycans on Ebola Virus Glycoprotein 2
Creators: Nicholas J Lennemann - Department of Microbiology, University of Iowa, Iowa City
Madeline Walkner - Department of Microbiology, University of Iowa, Iowa City
Abigail R Berkebile - Department of Microbiology, University of Iowa, Iowa City
Neil Patel - Department of Microbiology, University of Iowa, Iowa City
Wendy Maury - Department of Microbiology, University of Iowa, Iowa City
Resource Type: Journal article
Publication Details: The Journal of infectious diseases, Vol.212 Suppl 2(suppl 2), pp.S204-S209
DOI: 10.1093/infdis/jiv201
PMID: 26038399
PMCID: PMC4564545
ISSN: 0022-1899
eISSN: 1537-6613
Grant note: T32AI007533 / NIAID NIH HHS R01 AI077519 / NIAID NIH HHS T32 AI007533 / NIAID NIH HHS
Language: English
Date published: 10/01/2015
Academic Unit: Microbiology and Immunology
Record Identifier: 9984083877202771

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