Persistent Infections

Lead Research Organisation: University of Glasgow

Abstract

Congenital, Genital and Transplant-Acquired Infections – Genomics of Human Cytomegalovirus
Dr Andrew Davison, Lead Investigator, in collaboration with Prof Sheila Graham and Prof Ruth Jarrett, MRC-University of Glasgow Centre for Virus Research (CVR), University of Glasgow.
Human cytomegalovirus (HCMV) can be a serious issue for people whose immune systems are immature or not working properly. It is a major cause of foetal infections, a leading cause of illness in transplant recipients, and a problem for AIDS patients.
HCMV has a large genome, but new methods make it possible for us to understand the role that differences among viral strains play in infection. To make this practical, we have created a rapid way of sequencing complete HCMV genomes directly from clinical samples. We plan to relate viral variation to the outcome of infection in various groups, particularly transplant recipients. This will
involve analysing viral genome sequences in over 1000 infected patients.
In other projects, we will use modern approaches to study the functions of unusual HCMV RNAs and work out whether this might provide new ideas for drugs to treat infections.
Finally, we will apply our techniques to a relative of HCMV called human herpesvirus 6 (HHV6). This will help us understand whether the 1% of humans who have an HHV6 genome integrated into all their cells, and are capable of passing it to their children, are at risk of particular diseases.

Technical Summary

Understanding the role that viral variation plays in human cytomegalovirus (HCMV) disease has been limited by the large size of the genome and the challenges of getting whole-genome data from patient samples. My group has created a high-throughput pipeline for sequencing complete HCMV genomes directly from clinical material. We plan to capitalise on this by relating the diversity, evolution and strain dynamics of HCMV to clinical outcome in various groups, particularly transplant recipients. This will involve analysing viral genome sequence data from at least 1200 patient samples.
We have also used modern genomics and transcriptomics technologies to help establish a particular HCMV isolate (Merlin) as a well characterized research strain for use in laboratory studies. Using Merlin, we plan to determine the functions of HCMV long noncoding RNAs (lncRNAs), in order to assess whether they provide points at which HCMV infections might be suppressed. This will involve detailed functional characterization of viral mutants with completely characterised genomes.
Finally, we plan to provide added value to the congenital, genital and transplant-acquired infections programme by developing a pipeline for sequencing human herpesvirus 6 (HHV6) genomes. This will contribute to understanding the evolution and function of inherited chromosomal integration by this virus in human populations, on which evidence for clinical relevance is starting to accumulate from population studies.

Publications

10 25 50
 
Description International Committee on Taxonomy of Viruses (ICTV)
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
 
Description UK NEQAS for CMV DNA quantification
Geographic Reach National 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
 
Description Biomedical Resource Development Grant (Dr Andrew Davison)
Amount £532,413 (GBP)
Funding ID 108418/Z/15/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2016 
End 01/2021
 
Description Collaborative Award in Science (Dr Andrew Davison)
Amount £2,669,767 (GBP)
Funding ID 204870/Z/16/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2017 
End 03/2022
 
Description Prediction of Spillover Potential and Interventional En Masse Animal Vaccination to Prevent Emerging Pathogen Threats in Current and Future Zones of US Military Operation
Amount $9,669,372 (USD)
Funding ID HR001118S0017 
Organisation Defense Advanced Research Projects Agency (DARPA) 
Sector Public
Country United States
Start 10/2018 
End 03/2022
 
Description Principals Early Career Mobility Fund (Dr Nicolás Suárez)
Amount £4,000 (GBP)
Organisation University of Glasgow 
Sector Academic/University
Country United Kingdom
Start 07/2017 
End 08/2017
 
Description Research Grant (Dr Nicolás Suárez)
Amount £12,336 (GBP)
Funding ID S17-22 
Organisation Tenovus 
Department Tenovus Scotland
Sector Charity/Non Profit
Country United Kingdom
Start 02/2018 
End 06/2018
 
Description Research Incentive Grant (Dr Nicolás Suárez)
Amount £8,194 (GBP)
Funding ID RIG007549 
Organisation Carnegie Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2018 
End 12/2018
 
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 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 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 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 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 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 February 2017 Trust me I'm a Doctor - Dr Chris Boutell 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact In September 2016 Dr Chris Boutell was approached by the BBC and asked to review content for a show that would air on BBC 2 called Trust me I'm a Doctor. The show contained a short segment on herpes virus and Dr Boutell was asked questions and provided commentary on content to ensure accuracy. The show aired on prime time television in February 2017.
Year(s) Of Engagement Activity 2017
URL https://www.facebook.com/centreforvirusresearch
 
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
 
Description September 2018 - Connor Bamford and Betty Lau blog post 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact CVR postdoc Connor Bamford published a blog post written by postdoc Betty Lau to highlight a visit from Prof Kawaoka winner of the 2018 Sir Michael Stoker Award. The post was shared on Facebook and Twitter -

https://cvrblog.myportfolio.com/visit-from-prize-winner-prof-kawaoka

the post will be followed up by a podcast in future.
Year(s) Of Engagement Activity 2018
URL https://www.facebook.com/centreforvirusresearch/
 
Description Tortoise 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
Year(s) Of Engagement Activity 2015
URL http://www.sciencedaily.com/releases/2015/10/151029102730.htm