Professor of Virology
Head of the Division of Virology
Department of Pathology
University of Cambridge
Characterisation of the novel mechanism of calicivirus protein synthesis
We have recently reported that caliciviruses use a novel protein-directed translation initiation mechanism that involves the binding of translation initiation factors to the VPg protein that is covalently linked to the 5’ end of the viral RNA (Goodfellow et al. EMBO Reports 2005, Chaudhry et al. JBC 2006). This mechanism has not seen in any other animal RNA virus, but shares some limited similarity with a mechanism proposed for members of the plant potyvirus family. We demonstrated that calicivirus translation initiation requires the interaction of host cell translation initiation factors with a virus encoded protein covalently linked to the viral RNA genome. Current work focuses on the proteomic analysis of the components of the calicivirus translation initiation complex, structural analysis of the roles of other translation initiation factors in calicivirus translation, as well as the identification of inhibitors of this novel translation mechanism as potential anti-viral therapeutics.
Characterisation of calicivirus replication complex formation
The replication of all positive stranded RNA viruses occurs on the surface of membranous vesicles formed in the cytoplasm of the infected cell. These vesicle form via virus induced modulation of the host cell secretory pathway. This project aims to characterise the viral and cellular proteins (and processes) involved in replication complex formation using a combination of imaging, molecular and biochemical approaches.
Identification and characterisation of RNA-protein interactions required for calicivirus replication
Due to their limited genome size, positive stranded RNA viruses rely very heavily on the host cell to provide many proteins which enable virus translation and replication to occur. These host cell factors usually interact with defined RNA sequences or structures within the viral genome, often in combination with viral proteins. This project aims to identify the cis-acting functional RNA structures within the viral genome as well as the viral and host cell proteins which interact with these structures, and then to subsequently determine the role of these interactions in the norovirus life cycle. This will not only give us a greater insight into how these viruses replicate but will also lead to the identification of method for rationale attenuation of noroviruses.
Funding for our research comes from numerous sources including the BBSRC, Marie Curie, MRC and Wellcome Trust.
- Group Members:
Armando Airas, Sarah Caddy, Constantina Christodolou, Edward Emmott, Yasmin Goodfellow, Nora McFadden, Lucy Thorne, Surrender Vashist
- Vashist S, Urena L, Chaudhry Y, Goodfellow I. Identification of RNA-protein interaction networks involved in the norovirus life cycle. J Virol. 2012 Aug 29. PubMed PMID: 22933270.
- Thorne L, Bailey D, Goodfellow I. High-resolution functional profiling of the norovirus genome. J Virol. 2012 Nov;86(21):11441-56. PubMed PMID: 22915807.
- Subba-Reddy CV, Yunus MA, Goodfellow IG, Kao CC. Norovirus RNA Synthesis Is Modulated by an Interaction between the Viral RNA-Dependent RNA Polymerase and the Major Capsid Protein, VP1. J Virol. 2012 Sep;86(18):10138-49. PubMed Central PMCID: PMC3446604.
- Arias A, Ureña L, Thorne L, Yunus MA, Goodfellow I. Reverse genetics mediated recovery of infectious murine norovirus. J Vis Exp. 2012 Jun 24;(64). pii: 4145. PubMed PMID: 22760450.