Mutation of a Single Envelope N-Linked Glycosylation Site Enhances the Pathogenicity of Bovine Leukemia Virus.

Autor:	de Brogniez A; Molecular Biology (GxABT) and Molecular and Cellular Epigenetics (GIGA), University of Liege, Gembloux and Liege, Belgium alix.debrogniez@ulg.ac.be luc.willems@ulg.ac.be., Bouzar AB; Molecular Biology (GxABT) and Molecular and Cellular Epigenetics (GIGA), University of Liege, Gembloux and Liege, Belgium., Jacques JR; Molecular Biology (GxABT) and Molecular and Cellular Epigenetics (GIGA), University of Liege, Gembloux and Liege, Belgium., Cosse JP; Molecular Biology (GxABT) and Molecular and Cellular Epigenetics (GIGA), University of Liege, Gembloux and Liege, Belgium., Gillet N; Molecular Biology (GxABT) and Molecular and Cellular Epigenetics (GIGA), University of Liege, Gembloux and Liege, Belgium., Callebaut I; IMPMC, CNRS UMR7590, Sorbonne Universités, Université Pierre et Marie Curie-Paris 6, MNHN-IRD, Paris, France., Reichert M; Department of Pathology, National Veterinary Research Institute, Pulawy, Poland., Willems L; Molecular Biology (GxABT) and Molecular and Cellular Epigenetics (GIGA), University of Liege, Gembloux and Liege, Belgium alix.debrogniez@ulg.ac.be luc.willems@ulg.ac.be.
Jazyk:	angličtina
Zdroj:	Journal of virology [J Virol] 2015 Sep; Vol. 89 (17), pp. 8945-56. Date of Electronic Publication: 2015 Jun 17.
DOI:	10.1128/JVI.00261-15
Abstrakt:	Unlabelled: Viruses have coevolved with their host to ensure efficient replication and transmission without inducing excessive pathogenicity that would indirectly impair their persistence. This is exemplified by the bovine leukemia virus (BLV) system in which lymphoproliferative disorders develop in ruminants after latency periods of several years. In principle, the equilibrium reached between the virus and its host could be disrupted by emergence of more pathogenic strains. Intriguingly but fortunately, such a hyperpathogenic BLV strain was never observed in the field or designed in vitro. In this study, we sought to understand the role of envelope N-linked glycosylation with the hypothesis that this posttranslational modification could either favor BLV infection by allowing viral entry or allow immune escape by using glycans as a shield. Using reverse genetics of an infectious molecular provirus, we identified a N-linked envelope glycosylation site (N230) that limits viral replication and pathogenicity. Indeed, mutation N230E unexpectedly leads to enhanced fusogenicity and protein stability. Importance: Infection by retroviruses requires the interaction of the viral envelope protein (SU) with a membrane-associated receptor allowing fusion and release of the viral genomic RNA into the cell. We show that N-linked glycosylation of the bovine leukemia virus (BLV) SU protein is, as expected, essential for cell infection in vitro. Consistently, mutation of all glycosylation sites of a BLV provirus destroys infectivity in vivo. However, single mutations do not significantly modify replication in vivo. Instead, a particular mutation at SU codon 230 increases replication and accelerates pathogenesis. This unexpected observation has important consequences in terms of disease control and managing. (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)
Databáze:	MEDLINE
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