Risk of emergence of a hyperpathogenic bovine leukemia virus by mutation of a single envelope N-linked glycosylation site

Pathogens have co-evolved with their host to allow efficient replication and transmission without inducing excessive pathogenicity that would indirectly impair their persistence. This is exemplified by the bovine leukemia virus (BLV) model that induces lymphoproliferative disorders in ruminants only after extended 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, this type of hyperpathogenic BLV strain could never been isolated in vivo nor designed in vitro. Using reverse genetics of an infectious molecular provirus, we have now identified a N-linked envelope glycosylation site that limits viral replication and pathogenicity. Onset of this particular mutation may thus represent a potential threat associated with emergence of hyperpathogenic BLV strains and possibly of new variants of the related primate T-lymphotropic viruses.