LCMV Glycosylation Modulates Viral Fitness and Cell Tropism

The glycoprotein (GP) of arenaviruses is glycosylated at 11 conserved N-glycosylation sites. We constructed recombinant lymphocytic choriomeningitis virus (rLCMV) featuring either additions or deletions of these N-glycans to investigate their role in the viral life cycle. N-glycosylation at two site...

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Bibliographic Details
Published in:PloS one Vol. 8; no. 1; p. e53273
Main Authors: Bonhomme, Cyrille J., Knopp, Kristeene A., Bederka, Lydia H., Angelini, Megan M., Buchmeier, Michael J.
Format: Journal Article
Language:English
Published: United States Public Library of Science 07.01.2013
Public Library of Science (PLoS)
Subjects:
Animals
Biochemistry
Biology
Bone (cortical)
Bone marrow
Cell Line
Cells, Cultured
Clonal deletion
Construction sites
Cortical bone
Cytotoxicity
Deletion mutant
Disease
Fibroblasts
Fitness
Glycan
Glycoproteins
Glycoproteins - genetics
Glycoproteins - metabolism
Glycosylation
Health aspects
HIV
Human immunodeficiency virus
Humans
Infections
Life cycle engineering
Life cycles
Lymphocytic Choriomeningitis - veterinary
Lymphocytic Choriomeningitis - virology
Lymphocytic choriomeningitis virus - genetics
Lymphocytic choriomeningitis virus - growth & development
Lymphocytic choriomeningitis virus - metabolism
Macrophages
Macrophages - virology
Medicine
Mice
Mice, Inbred C57BL
Models, Molecular
Molecular biology
Mutants
Mutation
N-glycans
Neurons
Neurons - virology
Polysaccharides
Polysaccharides - genetics
Polysaccharides - metabolism
Protection and preservation
Proteins
Tropism
Viral Proteins - genetics
Viral Proteins - metabolism
Virology
Viruses
United States > US
California
ISSN:1932-6203, 1932-6203
Online Access:Get full text
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Description
Summary:The glycoprotein (GP) of arenaviruses is glycosylated at 11 conserved N-glycosylation sites. We constructed recombinant lymphocytic choriomeningitis virus (rLCMV) featuring either additions or deletions of these N-glycans to investigate their role in the viral life cycle. N-glycosylation at two sites, T87 and S97, were found to be necessary to rescue rLCMV. Three of nine successfully rescued mutants, S116A, T234A, and S373A, under selective pressures in either epithelial, neuronal, or macrophage cells reverted to WT sequence. Of the seven stable N-glycan deletion mutants, five of these led to altered viral fitness and cell tropism, assessed as growth in either mouse primary cortical neurons or bone marrow derived macrophages. These results demonstrate that the deletion of N-glycans in LCMV GP may confer an advantage to the virus for infection of neurons but a disadvantage in macrophages.
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Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: CB MB. Performed the experiments: CB. Analyzed the data: CB. Contributed reagents/materials/analysis tools: CB. Wrote the paper: CB KK LB MA MB.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0053273