Immune senescence and cardiovascular morbidity as a result of chronic cytomegalovirus infection

Asymptomatic chronic cytomegalovirus (CMV) infection in otherwise healthy individuals may have important implications for their long-term health. Recent research suggests that CMV may play a critical role in determining human longevity through the remodelling of vasculature and the ageing of the immune system. Immune ageing is known as immune senescence. Acute CMV infection typically occurs in the setting of severe immune suppression, end-stage human immunodeficiency virus infection, post organ transplantation or autoimmune disease. In these instances, CMV infection is severely debilitating and often fatal. On the other hand, chronic CMV infection is mostly indolent, and affects the majority of the world’s population without clinically evident morbidity. This review focuses on the role of CMV in immune senescence and its relationship to cardiovascular mortality and morbidity. In the elderly, CMV seropositivity has been recently linked to immune senescence. The mechanisms by which CMV alters the function and architecture of the body’s immune system and promotes a state of chronic inflammation are only now becoming apparent. Much more research is needed to fully understand the broader impact of this virus. It is proposed that CMV-mediated immune processes are responsible for the development of inflammation-driven disorders – including diabetes, osteoporosis, cognitive dysfunction and cardiovascular disease – in the elderly. Chronic CMV infection elicits recurrent effector T cell responses that may generate collateral damage. Over the course of decades, the host response to chronic CMV infection leads to the development and accumulation of apoptosis-resistant CD28- T cell clones that fail to respond to normal T cell proliferative responses. The cells that are present in atheromatous plaques release cytokines that generate a pro-inflammatory milieu in the intima of arteries, increasing the risk of acute coronary syndromes. In the elderly, the presence of CD28- T cell clones is also associated with weak neo-antigen responses and poor clinical outcomes.