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