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Virology

Introduction

Virus diseases continue to be major global health problems. The World Health Organisation (WHO) identifies infection with measles virus, hepatitis B virus and rotaviruses among the ten most common causes of mortality worldwide; each of them causes more than a million deaths per year. The human immunodeficiency virus (HIV) seems certain to join them in the 'top ten' as the AIDS pandemic develops. Viruses causing significant mortality and morbidity continue to emerge (or to be described for the first time) including Ebola, Hepatitis C virus and Kaposi's sarcoma-associated herpes virus. On the plus side, research on virus-cell interactions has provided, and may continue to provide, valuable insights into normal cellular mechanisms.

The Course

The course aims to develop such an understanding of the ongoing threat to individuals and populations posed by virus infection through its comprehensive and up-to-date presentation of virology. It starts with the molecular biology of viruses (organisation and expression of genetic information, mechanisms of entry and exit, principles of virus structure). The consequences of virus infection are then considered at the level of the individual cell (cytopathic effects, cell transformation) and in the multicellular host (immune responses, mechanisms of pathogenesis, latent and persistent infections, tumour induction). These principles are illustrated with reference to the major virus diseases of humans and animals. The final section concentrates on epidemiological aspects of virus infection (routes of transmission, antigenic variation) and approaches to the control of virus disease (vaccination, chemotherapy, public health measures). Biotechnological aspects of viruses are covered in lectures on gene therapy and vaccine development.

Research Projects

Staff and students in the Virology Division of the Pathology Department pursue a wide range of research interests. DNA virus topics include herpes simplex virus latency, the roles of herpesvirus glycoproteins in entry and egress, mechanisms controlling infection, replication and latency of a mouse gamma 2- herpesvirus and the cellular and multicellular interactions of human papillomaviruses. RNA virus topics include influenzavirus replication, virus entry mechanisms and virus use of unusual translational mechanisms. We have extensive contacts with virologists in the Department of Medicine. Their interests include human cytomegalovirus transcription and the roles of RNA structures in retrovirus replication. Research projects will be offered in both the Virology Division and the Department of Medicine These projects will be carried out on the Addenbrooke’s site.

Examples of Current/Previous Projects

2014-2015
  • Endocytosis of viral proteins in assembly of HSV-1.
  • Does the human Golgi Anti-apoptotic protein have a role in cancer?
  • Adenovirus-36 and biopsy-proven non-alcoholic fatty liver disease.
  • Understanding events during Papillomavirus Lesion Regression.
  • Characterization of the norovirus VPg-elF4E interaction and its role in the norovirus life cycle.
  • Clinical CMV sequencing for detecting drug resistance in primary infection post-multivisceral transplant.
  • A new function for vaccinia virus protein F13.
  • Examining the impact of KSHV-TK, a viral phosphoprotein, upon celluar Crk signalling pathways.
  • The human HOPS complex is required for Ebola virus infection: how is this complex recruited to intracellular membranes?
  • Analysis of the HIV-1 RNA genome structure inside cells.
  • In vitro analysis of the cardiovirus ribosomal frameshifting mechanism.
  • Programmed ribosomal frameshifting in Porcine Reproductive and Respiratory Syndrome Virus (PRRSV).
2013-2014
  • Translational control of virus gene expression by ribosome profiling.
  • The role of cellular factors in viral termination codon readthrough.
  • Definition of neuronal subpopulations latently infected by herpes simplex virus type-1.
  • Regulation of host and viral gene expression during lytic HSV-1 infection.
  • Polyomaviruses BK and JC: Investigation into viral release pathways and formation of an infectious virion.
  • Identification of functional residues in the norovirus VF1 protein.
  • Investigating the molecular and epidemiological biology of canine calicivirus.
  • TRIM21-mediated antiviral immunity.
  • Studies on HIV latency.
  • Importance of the Murid Herpesvirus-4 (MuHV-4) M3 protein during infection of the upper respiratory tract.
  • Analysis of the effects of down-regulation of Notch Ligand Delta-like 1 (Dll1) during human cytomegalovirus (HCMV) latency.
  • Control of Human cytomegalovirus viral dissemination by virus specific CD4 and CD8+ T cells.
  • Immune evasion by vaccinia virus.