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

- Introduction :

Pathogens have co-evolved 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. Infection of sheep and cattle with BLV is a model system for the related human T-lymphotropic virus type 1 (HTLV-1) responsible for Adult T-cell Leukemia (ATL).

- Aims :

The goal of this work is to investigate the role of N-glycans of the viral envelope protein during viral replication and pathogenesis.

- Methods and results :

Using glycosylation inhibitors and lectins, we showed that N-glycosylation is involved in viral infection (i.e. cell-to-cell fusion). Using reverse genetics of an infectious molecular provirus, we next demonstrated that a particular N-linked envelope glycosylation site (N230) limits viral replication and pathogenicity in vitro and in vivo. We have thus generated a viral mutant that is more pathogenic than the wild type strain.

- Conclusions :

To our knowledge, this is the first time that a hyperpathogenic BLV has been identified. This unexpected observation has important consequences in terms of disease control and managing. Indeed, during evolution, pathogens and their hosts should achieve an equilibrium allowing the coexistence of the two species. Occurrence 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 HTLV-1.