CMV (Cytomegalovirus)

Cytomegalovirus is a ubiquitous beta-herpesvirus that establishes lifelong latency after primary infection, with seroprevalence ranging from roughly 40–70% in high-income populations, with rates rising substantially in older age groups, to over 90% in parts of Africa, Asia, and South America. Because CMV is never fully cleared, the immune system sustains a large, chronically activated CD8+ T-cell response against viral antigens, a process called memory inflation. Over decades, these oligoclonal CMV-specific CD8+ expansions progressively occupy a growing fraction of the total T-cell repertoire, displacing naive cells and narrowing immunological breadth — a phenomenon linked to poor vaccine responses, frailty, and all-cause mortality in older adults. CMV seropositivity is considered one of the strongest extrinsic drivers of immunosenescence and is now incorporated into immune-age profiling approaches such as the immune risk profile.