Age-Stratified Seroprevalence of Cytomegalovirus and Epstein–Barr Virus in a Population-Based Cohort in Japan, 2017–2024

Abstract Background Cytomegalovirus (CMV) and Epstein–Barr virus (EBV) are ubiquitous latent herpes viruses, but contemporary population-based seroprevalence data in Japan remain limited, particularly in younger age groups. This study aimed to characterize age- and sex-specific CMV and EBV seroprevalence in a population-based Japanese cohort and to describe combined serostatus patterns across age groups. Methods We conducted a cross-sectional seroepidemiological analysis of the Tohoku Medical Megabank Project Birth and Three-Generation (TMM BirThree) cohort. Serum samples collected between 2017 and 2024 were tested for CMV IgG (age 4–40 years; n = 2,247) and EBV viral capsid antigen IgG (age 4–30 years; n = 1,647) using commercial ELISA. Seroprevalence was stratified by age and sex. Combined CMV/EBV serostatus patterns were described, and sensitivity analyses assessed temporal consistency and intra-family clustering. Results CMV seroprevalence increased during childhood and adolescence and plateaued at approximately 70–80% in early adulthood, whereas EBV seroprevalence rose steadily, exceeding 70% in late adolescence and 90% in the late 20s, with minimal sex differences. Dual seropositivity increased with age, the CMV−/EBV− group declined, and CMV−/EBV+ remained more common than CMV+/EBV− across all age groups. These patterns were consistent in sensitivity analyses. Conclusions CMV and EBV exhibit distinct age-related seroepidemiologic patterns in Japan despite overlapping transmission routes. The early plateau of CMV seroprevalence and near-universal EBV seropositivity by young adulthood indicate divergent infection dynamics with implications for congenital CMV prevention, infectious mononucleosis risk, and ongoing vaccine strategy.