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Department of Pathology

 

Research

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:
    Rhys Izuagbe, Yasmin Goodfellow, Aminu Jahun, Malte Pinckert, Myra Hosmillo, Anna Kovalenko, Iliana Georgana

Publications

Key publications: 

1.          Hamilton WL, …..  Goodfellow IG, Torok ME; COVID-19 Genomics Consortium UK (2021).  Genomic epidemiology of COVID-19 in care homes in the East of England. Elife. 2021 Mar 2;10:e64618. doi: 10.7554/eLife.64618. PMID: 33650490 

2.          Kemp SA, …… Goodfellow IG, Gkrania-Klotsas E, Illingworth CJR, McCoy LE, Gupta RK (2021). SARS-CoV-2 evolution during treatment of chronic infection. Nature. 2021 Feb 5. doi: 10.1038/s41586-021-03291-y. Online ahead of print. PMID: 33545711

3.          Ziv O, Price J, Shalamova L, Kamenova T, Goodfellow I, Weber F, Miska EA (2020). The Short- and Long-Range RNA-RNA Interactome of SARS-CoV-2. Molecular Cell. 2020 Dec 17;80(6):1067-1077.e5. doi: 10.1016/j.molcel.2020.11.004. Epub 2020 Nov 5. PMID: 33259809; PMCID: PMC7643667.

4.          Meredith LW, Hamilton WL, Warne B, Houldcroft CJ, Hosmillo M, Jahun AS, Curran MD, Parmar S, Caller LG, Caddy SL, Khokhar FA, Yakovleva A, Hall G, Feltwell T, Forrest S, Sridhar S, Weekes MP, Baker S, Brown N, Moore E, Popay A, Roddick I, Reacher M, Gouliouris T, Peacock SJ, Dougan G, Török ME, Goodfellow I (2020). Rapid implementation of SARS-CoV-2 sequencing to investigate cases of health- care associated COVID-19: a prospective genomic surveillance study. Lancet Infect Dis. 2020 Nov;20(11):1263-1272. doi: 10.1016/S1473-3099(20)30562-4. Epub 2020 Jul 14. PMID: 32679081.

5.          Hosmillo M, Chaudhry Y, Nayak K, Sorgeloos F, Koo BK, Merenda A, Lillestol R, Drumright L, Zilbauer M, Goodfellow I (2020). Norovirus Replication in Human Intestinal Epithelial Cells Is Restricted by the Interferon-Induced JAK/STAT Signaling Pathway and RNA Polymerase II-Mediated Transcriptional Responses. mBio. 2020 Mar 17;11(2):e00215-20. doi: 10.1128/mBio.00215-20. PMID: 32184238; PMCID: PMC7078467.

6.          Arthur SE, Sorgeloos F, Hosmillo M, Goodfellow IG (2019). Epigenetic Suppression of Interferon Lambda Receptor Expression Leads to Enhanced Human Norovirus Replication In Vitro. mBio. 2019 Oct 1;10(5):e02155-19. doi: 10.1128/mBio.02155-19. PMID: 31575769; PMCID: PMC6775457.

7.          Hosmillo M, Lu J, McAllaster MR, Eaglesham JB, Wang X, Emmott E, Domingues P, Chaudhry Y, Fitzmaurice TJ, Tung MK, Panas MD, McInerney G, Locker N, Wilen CB, Goodfellow IG (2019). Noroviruses subvert the core stress granule component G3BP1 to promote viral VPg-dependent translation. Elife. 2019 Aug 12;8:e46681. doi: 10.7554/eLife.46681. PMID: 31403400; PMCID: PMC6739877.

8.          Michaela J. Conley, Marion McElwee, Liyana Azmi, Mads Gabrielsen, Olwyn Byron, Ian G. Goodfellow and David Bhella (2019). Calicivirus VP2 forms a portal-like assembly following receptor engagement. Nature Jan;565(7739):377-381. PMID:30626974

9.          L Thorne A, Nalwoga A J, Mentzer,  Rougemont A de, Hosmillo M, Webb E, Nampiija M, A Muhwezi A, Carstensen T, Gurdasani D,  Hill AV,  Sandhu MS, Elliott A, Goodfellow I (2018). The First Norovirus Longitudinal Seroepidemiological Study from Sub-Saharan Africa Reveals High Seroprevalence of Diverse Genotypes Associated with Host Susceptibility Factors. J Infect Dis. 2018 Jul 24;218(5):716-725. doi: 10.1093/infdis/jiy219. PMID:29912471

10.       Edward Emmott, Frederick Sorgeloos, Sarah L. Caddy, Surender Vashist,Stanistav Sosnovtsev, Richard Lloyd,Kate Heesomand Ian Goodfellow (2017). Norovirus-mediated modification of the translational landscape via virus and host-induced cleavage of translation initiation factors. Molecular and cellular proteomics 2017 Apr;16(4 suppl 1):S215-S229.  PMC5393397

Professor of Virology
Division of Virology
Deputy Head of Department (Research)
Professor Ian  Goodfellow

Contact Details

Division of Virology
Department of Pathology
University of Cambridge
Addenbrooke's Hospital
Hills Road,
Cambrige
UK
+44 (0) 1223 762653
Takes PhD students
Available for consultancy

Affiliations

Specialities: