Insight into viral protein translation

European researchers developed a novel technique for investigating the mechanism of viral protein synthesis. Their results have broad implications for the next generation of anti-viral therapies.

Fundamental Research

Health

Norovirus, a member of the family of small RNA viruses, is the major cause of viral gastroenteritis worldwide. Recent evidence from older people and immunocompromised patients such as those receiving chemotherapy indicates high mortality and morbidity rates. Despite extensive research, currently there are no treatments that effectively control norovirus infection. During viral infection, the host cell machinery is exploited to produce viral proteins required for replication and spread. Viruses compete with host cell messenger RNAs for the protein production machinery through poorly understood mechanisms. Norovirus promotes viral protein production through the interaction of cellular factors with a viral protein called VPg, which is attached to the viral RNA genome. Towards this goal, the EU-funded INITIATING NOROVIRUS (Delineating the novel mechanism of VPg dependent virus translation initiation) project set out to develop a powerful technique for studying protein translation mechanisms in virally infected cells. The mammalian in vitro translation reconstitution system facilitated the investigation of the mechanisms of viral protein synthesis and helped identify cellular proteins essential for this function. Researchers purified mammalian translation factors and ribosomal subunits and assessed the impact of each of these proteins on VPg-dependent translation. They also established experimental techniques for determining the structure present at the VPg-proximal region responsible for its interaction with viral RNA. Mapping of this VPg protein-RNA interaction will help build a detailed picture of how these viral translation complexes are assembled. Overall, a deeper understanding of the molecular mechanisms required for VPg-dependent protein synthesis is expected to help researchers identify how canonical cellular translation differs from viral protein synthesis. In turn, this will provide targets for the development of new anti-viral therapies.