Congenital human cytomegalovirus (HCMV) is a herpes virus infecting the majority of the world’s population. Even though it is relatively harmless to healthy individuals, it can be extremely dangerous for people whose immune systems have been compromised (e.g. in organ transplants) or not yet developed (foetuses and newborns). The focus of this research is HCMV infection before birth (in utero) or during birth (congenital infection). Even though relatively unknown to the public, it is the primary cause of long-term neurodevelopmental sequelae, including mental retardation, microcephaly and sensorineural hearing loss. Natural killer (NK) cells play an important role in control of CMV infection, and adaptive features of NK cells in response to CMV infection are recently being increasingly recognized. However, the extent to which congenital CMV infection affects and shapes NK-cell mediated immunity is largely unknown. To address this issue, we will use MCMV infected newborn mice and follow the impact of infection on the maturation and functional properties of NK cells.

The goal of this project is to characterize functional, phenotypic and transcriptional changes in NK cells following perinatal MCMV infection. Furthermore, the goal is to characterize the factors and mechanisms that induce NK cell exhaustion and to determine if NK cell exhaustion can be prevented or reverted. In addition, in the proposed study we will determine the role of NK cells in MCMV control and virus induced pathology in newborn mice.

The project entails collaboration with several international research groups from the USA and Germany as well as clinical centres in Zagreb and Rijeka. The proposed research is an important step towards better understanding of pathogenesis of congenital CMV infection, but will as well contribute to better understanding of NK cell biology in general, in pathological conditions in particular.