Studies on respiratory syncytial virus

Lead Research Organisation: MRC Virology Unit

Abstract

We want to find out more about how the respiratory syncytial virus (RSV) works. Everyone will get RSV by the age of 3 and we continue to get infected with RSV throughout our lifetime. In most people it only causes cold symptoms like a runny nose and sore throat but in babies and the elderly it can become very serious resulting in hospitalisation. At present we do not have a vaccine or an effective treatment for RSV.||To be successful the virus must be able to get in and out of cells, copy itself and hide from the bodys defences. The RSV virus makes just eleven proteins and these can be broadly separated into doing these different jobs. We are using molecular biology and microscopy techniques to learn more about these proteins and how they work together. We are targeting the proteins needed for the virus to get in and out of cells and to make new virus. By understanding how these proteins interact with each other and the cell we hope to identify targets to block the virus infection.

Technical Summary

Respiratory syncytial virus (RSV) has been recognised as the major cause of lower respiratory tract infection in young infants for many years. However, only recently has the importance of the impact of this virus in the elderly population become evident. No vaccine is available for RSV. Currently RSV-specific drugs are limited to antibody-based treatments, primarily used to prevent infection in very high-risk infants through the RSV season.||RSV is a member of the Paramyxoviridae. Other notable viruses in this family include Measles virus, Mumps virus and some of the newly emerging viruses such as Nipah virus and Hendra virus. The RSV genome is composed of a single-strand of negative-sense RNA. The genome encodes ten viral genes producing eleven proteins. The overall aim of our research is to identify how these proteins interact with one other and with the host-cell during RSV infection. A wide range of molecular biology, biochemical and microscopy techniques are being used to do this.||Current areas of research include:|The role of the SH protein, a novel glycoprotein found in a subset of mononegaviruses including Mumps virus and Human Metapneumovirus. The function of SH is not known. However, it has been shown to be important for pathogenesis of the virus. From analysis of the protein sequence, SH has been proposed to be a member of an expanding group of viral proteins known as viroporins. We are investigating the possible viroporin activity of SH and the function of this protein during RSV infection.||The regulation of RNA synthesis. For several years, we have known that three proteins are absolutely required for RNA synthesis, namely the nucleoprotein (N), phosphoprotein (P) and the large polymerase (L). A fourth protein transcription-elongating factor (M2-1) is also required for transcription of the complete genome. Much work has been performed to investigate the RNA signals involved in replication and transcription. Building on this work, we are interested in investigating how these processes are regulated during infection and determining if other viral proteins are involved.||RSV and programmed cell death. RSV-infected lungs stain extensively for apoptotic markers. RSV also causes apoptosis in tissue culture, triggering both the extrinsic and intrinsic pathways. We are exploring the effect of RSV infection on components of the apoptosis pathway.

Publications

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Description Interaction between F-actin and respiratory syncytial virus 
Organisation University of Edinburgh
Department School of Biological Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise in the study of respiratory syncytial virus
Collaborator Contribution Provision of field emission scanning electron microscopy for ultrastructural studies.
Impact Publications 16514154 and 17825340
Start Year 2006
 
Description Lipid content of raft membranes during respiratory syncytial virus infection 
Organisation Nanyang Technological University
Country Singapore 
Sector Academic/University 
PI Contribution Expertise in respiratory virus and electron microscopy
Collaborator Contribution Expertise in lipid analysis
Impact Publication 19178924
Start Year 2006
 
Description Secretion of respiratory syncytial virus fusion protein from insect cells 
Organisation DSO National Laboratories
Country Singapore 
Sector Charity/Non Profit 
PI Contribution Provision of expertise in respiratory syncytial virus
Collaborator Contribution Expression in insect cells using baculovirus technology
Impact Publication 17502677
Start Year 2006