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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Vydané v:	PloS one Ročník 8; číslo 1; s. e53273
Hlavní autori:	Bonhomme, Cyrille J., Knopp, Kristeene A., Bederka, Lydia H., Angelini, Megan M., Buchmeier, Michael J.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Public Library of Science 07.01.2013 Public Library of Science (PLoS)
Predmet:	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
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Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 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