Genomics of human cytomegalovirus

Lead Research Organisation: MRC Virology Unit

Abstract

We are aiming to find out whether certain strains of human cytomegalovirus (HCMV) cause more serious disease than others.

Infection with HCMV is not a problem for most people, but it can be a serious danger to people whose immune systems are not working properly. Those at risk include AIDS patients, people who have had a transplant, and babies. Drugs that kill HCMV can be used in certain situations, but not in pregnant women. There is no vaccine.

HCMV is a complicated virus, and has the largest DNA molecule of any known human virus. Most of the research done so far in laboratories throughout the world has relied on strains that are highly mutated and behave differently from real virus.

Our research focuses on HCMV as present in people, with the aims of finding out how many genes there are and how they are expressed, discovering how many strains there are and whether some are more likely to cause serious disease than others, and developing new tools for monitoring the growth of virus in people.

Methods for studying genes are advancing very fast at the moment, and we are using the latest. Our research will help us understand how what HCMV does when people are infected, and give new ideas for detection and treatment.

Technical Summary

Human cytomegalovirus (HCMV) is an important pathogen in immunocompromised people such as AIDS patients and transplant recipients, and is a major infectious cause of congenital abnormalities. The HCMV genome is the largest of any human virus, at 236 kbp in size, and contains approximately 170 genes encoding functional proteins. Our focus is on wild type HCMV as it exists in humans.

Our aims are (i) to define the genetic content of HCMV strains, including discovering new genes (ii) to examine transcription patterns across the genome under various conditions that relate to clinical situations, (iii) to understand the striking degree of variation that is evident in certain genes, (iv) to elucidate any connection that particular strains or variants might have with the outcome of disease, (v) to develop new tools for characterizing strains or variants in clinical samples, and (v) to study the dynamics of infections with multiple strains in humans.

To address these aims, we are using next-generation sequencing techniques to obtain data on the sequences and transcription patterns of HCMV genomes. We use enrichment methods to isolate HCMV DNA from clinical material obtained from clinical collaborators, chief among whom are Dr Colin Geddes (NHS, Glasgow), Prof Thomas Schulz (Hannover Medical School) and Prof Giuseppe Gerna (IRCCS Policlinico San Matteo, Pavia). We are also investigating the expression of HCMV RNAs across the genome in various cell types, using high-throughput methods.

This programme of basic research combines strengths in the areas of virology, genome sequencing and bioinformatics. The output in terms of knowledge and materials will enhance our understanding of HCMV infection in clinical situations and provide new insights into treating HCMV disease.

Publications

10 25 50
 
Guideline Title A report of the Expert Committee on Biological Standardization, Geneva, 18 to 22 October 2010. Collaborative Study to Evaluate the Proposed 1st WHO International Standard for Human Cytomegalovirus (HCMV) for Nucleic Acid Amplification (NAT)-Based Assays
Description First international diagnostic standard for human cytomegalovirus
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical guidelines
 
Description International Committee on Taxonomy of Viruses (ICTV)
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
 
Description Royal Society of Edinburgh International Exchange Programme (Dr Andrew Davison)
Amount £1,000 (GBP)
Organisation Royal Society of Edinburgh (RSE) 
Sector Learned Society
Country United Kingdom
Start 10/2007 
End 10/2007
 
Description APHA 
Organisation Animal and Plant Health Agency
Country United Kingdom 
Sector Public 
PI Contribution Generating, analysing and publishing data
Collaborator Contribution Generating, analysing and publishing data
Impact 23552421 25199796
Start Year 2012
 
Description Budapest 
Organisation Hungarian Academy of Sciences (MTA)
Department Institute for Veterinary Medical Research
Country Hungary 
Sector Academic/University 
PI Contribution Generation, analysing and publishing data
Collaborator Contribution Generation, analysing and publishing data
Impact 21450837, 22894926
Start Year 2008
 
Description Cardiff 
Organisation Cardiff University
Department School of Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Generating, analysing and publishing data
Collaborator Contribution Generating, analysing and publishing data
Impact 18069056, 18649324, 19553388, 19906940, 20479471, 20679731, 22109557, 22345649, 23885075, 24787765, 25121749, 25875600, 25894764, 26842472, 28186488, 29691324, 30122656
 
Description Davis 
Organisation University of California, Davis
Country United States 
Sector Academic/University 
PI Contribution Research work, data analysis and preparation of manuscript
Collaborator Contribution Provision of data, data analysis and preparation of manuscript
Impact 17329333, 19565695, 23269803
Start Year 2006
 
Description Gainesville 
Organisation University of Florida
Department Department of Infectious Diseases and Pathology
Country United States 
Sector Academic/University 
PI Contribution Generation, analysis and publication of data
Collaborator Contribution Generation, analysis and publication of data
Impact 28774992, 29051247, 29748409
Start Year 2012
 
Description Glasgow 
Organisation NHS Greater Glasgow and Clyde (NHSGGC)
Department Western Infirmary, Glasgow
Country United Kingdom 
Sector Hospitals 
PI Contribution Generating, analysing and publishing data
Collaborator Contribution Generating, analysing and publishing data
Impact 18649324
Start Year 2006
 
Description Hanover 
Organisation Hannover Medical School
Country Germany 
Sector Academic/University 
PI Contribution Generating, analysing and publishing data
Collaborator Contribution Generating, analysing and publishing data
Impact 18649324, 19906940, 28368496
Start Year 2006
 
Description Johns Hopkins 
Organisation Johns Hopkins University
Country United States 
Sector Academic/University 
PI Contribution Generating, analysing and publishing data
Collaborator Contribution Generating, analysing and publishing data
Impact 19818982
Start Year 2006
 
Description Leuven 
Organisation University of Leuven
Country Belgium 
Sector Academic/University 
PI Contribution Generating, analysing and publishing data
Collaborator Contribution Generating, analysing and publishing data
Impact 22787220 23387531
Start Year 2011
 
Description Liège 
Organisation University of Liege
Department Laboratory of Immunology - Vaccinology
Country Belgium 
Sector Multiple 
PI Contribution Generating, analysing and publishing data
Collaborator Contribution Generating, analysing and publishing data
Impact 24225498, 25700279, 26111587, 26339050, 27924936, 28182952, 28690142, 28794046, 29472472, 29716648
Start Year 2012
 
Description Liverpool 
Organisation University of Liverpool
Country United Kingdom 
Sector Academic/University 
PI Contribution Generating, analysing and publishing data
Collaborator Contribution Generating, analysing and publishing data
Impact 19940063, 22258857, 25767243
Start Year 2008
 
Description Minnesota 
Organisation University of Minnesota
Country United States 
Sector Academic/University 
PI Contribution Generating, analysing and publishing data
Collaborator Contribution Generating, analysing and publishing data
Impact 18649324
Start Year 2006
 
Description Oslo 
Organisation Norwegian Veterinary Institute
Country Norway 
Sector Private 
PI Contribution Generating, analysing and publishing data
Collaborator Contribution Generating, analysing and publishing data
Impact None yet
Start Year 2013
 
Description Pavia 
Organisation Fondazione IRCCS Policlinico San Matteo
Department Servizio di Virologia
Country Italy 
Sector Charity/Non Profit 
PI Contribution Generating, analysing and publishing data
Collaborator Contribution Generating, analysing and publishing data
Impact 18649324, 20479471
Start Year 2006
 
Description Penn 
Organisation Penn State University
Country United States 
Sector Academic/University 
PI Contribution Generating, analysing and publishing data
Collaborator Contribution Generating, analysing and publishing data
Impact 24227835
Start Year 2012
 
Description St Andrews 
Organisation University of St Andrews
Country United Kingdom 
Sector Academic/University 
PI Contribution Generating, analysing and publishing data
Collaborator Contribution Generating, analysing and publishing data
Impact 23449801, 24453358, 27445371, 30742688
Start Year 2012
 
Description UCL 
Organisation University College London
Department MRC Centre for Medical Molecular Virology
Country United Kingdom 
Sector Public 
PI Contribution Generating, analysing and publishing data. Funded by Wellcome collaborative grant since April 2017.
Collaborator Contribution Generating, analysing and publishing data
Impact 18649324, 19906940, 20479471
Start Year 2006
 
Description Virginia 
Organisation Virginia Commonwealth University
Department School of Medicine
Country United States 
Sector Hospitals 
PI Contribution Generating, analysing and publishing data
Collaborator Contribution Generating, analysing and publishing data
Impact 22187535, 28391502
Start Year 2010
 
Description Yale 
Organisation Yale University
Department School of Medicine
Country United States 
Sector Academic/University 
PI Contribution Generating, analysing and publishing data
Collaborator Contribution Generating, analysing and publishing data
Impact 24212889, 29474519
Start Year 2012
 
Description Elephant herpesvirus 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Press release

NA
Year(s) Of Engagement Activity 2013
URL http://www.gla.ac.uk/news/headline_274500_en.html
 
Description March 2017 - Nico Suarez (Davison lab) - Radio Interview 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact In March 2017 Dr Nicolas Suarez was interviewed by a Gran Canaria- based radio show to discuss his research http://play.cadenaser.com/audio/000WB1459720170110111218/ the interview was also shared on CVR Facebook and Twitter accounts.
Year(s) Of Engagement Activity 2017
URL https://www.facebook.com/centreforvirusresearch
 
Description Nuffield Bursary students 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Schools
Results and Impact School pupils took up summer laboratory projects in separate years

Engagement with the scheme opens the door for similar contributions from my group in future
Year(s) Of Engagement Activity 2011,2012,2016
URL http://www.nuffieldfoundation.org/nuffield-research-placements