The bluetongue virus (BTV) is capable of infecting various domestic and wild ruminants (sheep, goats and cattle), causing a non-contagious disease in which many symptoms have already been described: degraded general condition, fever, localized inflammation , ulcers, edema of the face, cyanosis of the tongue (hence its English name, Bluetongue), respiratory disorders, udder oedema, testicular damage in rams, reproductive disorders. FCO virus is an arbovirus, which means that it is transmitted through arthropods. Recent epidemics due to human or animal viruses, such as Zika, Dengue Chikungunya, West Nile or Schmallenberg are arboviruses. By studying the molecular interactions between the FCO virus and the cells of the mammalian host that it infects, a joint Anses/Enva/Inra research team, UMR Virologie, has revealed a new mechanism for hijacking the machinery cells for the benefit of the replication of the FCO virus.
Scientists have shown an interaction between a viral protein, called NS3, and a host protein, BRAF. Since the latter is an essential player, notably responsible for cell survival, proliferation and differentiation, the virus has naturally evolved to circumvent these functions for its own benefit: survival, replication and propagation. It is the presence of the NS3 protein, then described as being a major virulence factor, which activates this BRAF-dependent pathway to increase virus replication.
These results were obtained through the use of different cellular and biochemical approaches. A specific inhibitor of the BRAF-dependent cellular pathway, U0126, significantly inhibits the expression of viral proteins as well as the replication of the FCO virus, thus underlining the use of this pathway by the virus to ensure its replication. These results might also be part of the answer to explain the hyper-inflammation observed in the case of a pathology linked to bluetongue. Deciphering these molecular virus-host interactions and the underlying mechanisms therefore opens up new perspectives for predicting virulence, simulating viral evolution (crossing the species barrier) and establishing effective measures for the control of arboviruses, in particular through the development of broad-spectrum antiviral molecules and new vaccine strains.”
Reference :
Novel Function of Bluetongue Virus NS3 Protein in Regulation of 1 the MAPK/ERK Signaling Pathway. Cindy Kundlacz, Marie Pourcelot, Aurore Fablet, Rayane Amaral Da Silva Moraes, Thibaut Léger, Bastien Morlet, Cyril Viarouge, Corinne Sailleau, Mathilde, Turpaud, Axel Gorlier, Emmanuel Breard, Sylvie Lecollinet, Piet A. van Rijn, Stephan, Zientara, Damien Vitour, Grégory Caignard. Journal of Virology. 5 juin 2019. doi: 10.1128/JVI.00336-19
