Analysis of cytomegalovirus pathogenesis in a human challenge system  

Immunosuppressive drugs that prevent the rejection of transplanted organs also reduce immune responses that normally protect patients from virus infections. With previous Wellcome Trust support, we pioneered a way of detecting the most important virus, human cytomegalovirus (HCMV) in the blood to identify those at risk of disease. Based on our research, a pre-emptive therapy involving prompt administration of antiviral drugs at the first detection of HCMV was introduced into clinical practice and reduced the development of serious diseases caused by this virus. Among the patients that all received the same immunosuppressive drugs, only some have HCMV detectable in the blood, showing that they have poor immune control of HCMV. This phenotype could be explained if there were genetic differences in some strains of the virus.

We will exploit recent changes in contemporary medical practice that mean samples can now be obtained from donors. A multidisciplinary team will assess how HCMV evolves after transplant from one person to another and relate the results to measures of how active different components of the immune system are against HCMV. 

As with our earlier research, we expect the results will explain the phenotypes observed and find immediate practical applications in the management of patients.