Sara van den Berg

175 7 Duration of CMV infection ABSTRACT CMV infection is thought to affect the immune system and to impact general health and specifically the prevalence of cardiovascular disease. These effects are believed to accumulate over time. The increased CMV-specific antibody levels observed in elderly are generally assumed to reflect experienced viral reactivation during life. Furthermore, high levels of terminally-differentiated T-cells and large expansions of CMV-specific T-cells are hallmarks of CMV infection, which are thought to increase over time, a process also referred to as memory inflation. We had the unique opportunity to study CMV-specific antibody levels over ~27 years in 268 individuals (aged 60-87 years at endpoint), and to link CMV-duration to T-cell numbers, CMV-specific T-cell functions, frailty and cardiovascular disease at endpoint. In our study, 136/268 individuals were long-term CMV-seropositive and 19 persons seroconverted during follow-up (seroconversion rate: 0.56%/year). Although CMV-specific antibody levels increased slightly over time, differences in CMV-specific antibody levels at endpoint were hardly explained by CMV-duration. CMV-duration was not related to the size and function of the memory T-cell pool at endpoint. Elevated levels of CMV-specific antibodies were associated with cardiovascular disease, but not with frailty. Age at CMV-seroconversion was positively associated with CMV-specific antibody levels, memory CD4 + T-cell numbers and frailty. In conclusion, CMV-specific memory T-cells develop shortly after CMV infection but do not seem to further increase over time. Age-related effects other than duration of CMV infection seem to contribute to CMV-induced changes in the immune system. Although CMV-specific immunity is not linked to frailty, it might be related to increased prevalence of cardiovascular disease.