AbstractGene expression concerning the ICP22 protein, encoded by the Gallid herpesvirus type 2, was described as being induced by a mechanism depending on the binding of a microRNA to the messenger RNA. Preliminary results described an expression increase at both the transcriptional and translational levels. Mechanisms that underlie this increase were not elucidated yet.
The first aim of this master thesis was the establishment of constructs reporting the natural miRNA-mediated enhancement in order to confirm and to decipher the ins and outs of this natural enhancement.
The first obtained results shed light at a secondary structure belonging to the messenger RNA, localized at the microRNA binding site. This hairpin structure was revealed to have a prominent role at both the transcriptional and translational levels. The microRNA was also shown to play a substantial role which was both direct and indirect.
Although they were not studied yet, several mechanistic models were suggested based on the results and on literature. These non-exclusive mechanisms involve both the microRNA and the described hairpin.
As the virus becoming increasingly virulent over time, concomitant with the approaching obsolescence of the current vaccines, it is important to find new ways to protect the impacted animals. The suggested mechanisms open a gate to new alternative ways to engineer new vaccine strains, attenuated by the expression of proteins deleterious for the viral life cycle.
|Date of Award||16 Jan 2020|
|Supervisor||Benoit Muylkens (Jury) & Srdan Pejakovic (Co-Supervisor)|