Human cytomegalovirus (HCMV) is one of the most common human viruses, infecting most people worldwide. In healthy individuals, infection usually causes no symptoms. However, HCMV can cause severe disease in people with weakened immune systems, such as transplant recipients, and is a leading infectious cause of birth defects when transmitted during pregnancy. A key feature of HCMV is its ability to establish lifelong latent infection, during which the virus remains hidden in the body and can later reactivate. Despite its major medical importance, there is currently no approved vaccine against HCMV and no antiviral drugs that specifically target the latent phase of infection.
A major barrier to progress has been an incomplete understanding of HCMV biology. HCMV has the largest genome of any virus known to infect humans, encoding hundreds of potential proteins, many of which were poorly characterized. In addition, although HCMV can infect many cell types, the outcome of infection varies widely. Cells of the myeloid lineage play a central role in viral latency and reactivation, yet the molecular reasons why some cells support latent infection while others allow productive viral replication were largely unknown at the start of this project.
The overall objective of the DissectCMV project was to address these gaps by creating a comprehensive functional map of viral and host factors that control HCMV infection. The project aimed to identify previously unrecognized functional elements in the viral genome, to understand the molecular determinants that govern whether infection becomes latent or productive, and to develop new technologies that enable systematic analysis of virus–host interactions. By the end of the project, these goals were achieved, leading to a revised understanding of HCMV latency as a quantitative and dynamic state shaped by early infection events and host cell properties, rather than a strictly silent or inactive phase.
