Analysis of cytomegalovirus pathogenesis in a human challenge system

A single blood test could determine which organ transplant patients are most at risk of a dangerous viral infection, allowing doctors to target treatment only to those who need it. Human cytomegalovirus (HCMV) is a common virus that usually causes mild or no symptoms in healthy people. But in transplant recipients, whose immune systems are deliberately suppressed to prevent organ rejection, HCMV can cause severe disease in the lungs, gut, or eyes. Current practice gives antiviral drugs to all patients with detectable virus in their blood, but many would never develop symptoms. The researchers have already shown that measuring specific biomarkers can identify which patients are truly at risk. This project now aims to understand *why* some patients get sick and others do not. The team will sequence the entire genome of HCMV from organ donors and recipients, tracking which viral strains infect or reactivate in each patient. They will also measure immune responses—antibodies, T cells, and natural killer cells—to see which ones correlate with protection. Because the clinical protocol already creates a controlled human challenge (patients are monitored from the moment of infection), this work offers a rare window into the natural history of HCMV in real time. If successful, the research could lead to more precise antiviral guidelines, sparing low-risk patients from unnecessary drug side effects. It may also reveal new targets for vaccines or immunotherapies against HCMV.