Structure function relationships of rotavirus RNAs - significance for the replication cycle. (360G-Wellcome-082031_Z_07_Z)

Rotaviruses are a major cause of acute gastroenteritis in infants and young children worldwide, leading to approximately half a million deaths per annum. There is no recognised specific antiviral treatment, and whilst rotavirus vaccines are under development they have not been universally applied yet. Rotaviruses package 11 different RNA segments into each virus particle. Reassortment between viruses occurs by exchange of corresponding RNA segments. Much published work indicates that this precis ion of packaging is a consequence of specific RNA structures in the RNA segments and that the RNA fulfils a structural role in the virion. We have performed preliminary analysis of potential RNA secondary structures in the termini of rotavirus segments and have identified conserved sequences and conserved potential intra and intermolecular pairings between the segments. Our aim is to define the RNA packaging signals in rotaviruses by structural analysis using free energy parameters, biochemical probing, sequence comparison and NMR spectroscopy. We will validate solved structures functionally by interaction with rotavirus core proteins and in replication assays and attempt to develop an in vitro packaging system. This work will identify new candidate therapeutic targets and has potential in vaccine development. It will contribute towards a reverse genetics system for rotaviruses.