A single letter change in the virus’s genetic code can mean the difference between a mild infection and a life-threatening illness in a transplant patient. Human cytomegalovirus (HCMV) is a major cause of birth defects and a leading threat to organ transplant recipients and people with weakened immune systems. Despite its importance, researchers have lacked the tools to quickly compare the full genomes of different viral strains from patient samples. This project fills that gap by using a new rapid sequencing method to analyse HCMV genomes from over 1,000 infected patients, linking specific genetic variations to disease outcomes. If successful, the work could transform how clinicians predict and manage HCMV risk in transplant wards—for instance, by identifying which viral strains are most dangerous before a patient receives a new organ. The project also explores unusual viral RNAs that may reveal new drug targets, and extends the same genomic approach to human herpesvirus 6 (HHV6), which is permanently integrated into the DNA of about 1% of people. Understanding whether this integration causes disease could eventually inform screening or treatment for that population.
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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.
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