Human cytomegalovirus infection: Risk factors, diagnosis, and impact on immunity and health

Human Cytomegalovirus (HCMV) is a ubiquitous β-herpesvirus, which is known to cause birth defects during pregnancy and serious infections, such as HCMV pneumonia, esophagitis, retinitis or encephalitis in immunocompromised patients including those with HIV-induced acquired immune deficiency syndrome (AIDS) and those on post-transplant immunosuppressive therapy. In immunocompentent individuals, primary HCMV infection is typically mild or asymptomatic. The virus is thought to persist in peripheral blood monocytes and myeloid progenitor cells, establishing a chronic HCMV infection. The peripheral blood monocytes, harboring the HCMV genome, circulate in the blood potentially leading to viral reactivation. Pregnancy, immune deficiency or suppression, and critical illness are known risk factors for HCMV infection/reactivation. Acute HCMV infection is assessed by HCMV viral load in the serum or plasma. Chronic HCMV infection is conventionally diagnosed by positive anti-HCMV IgG serology. HCMV seroprevalence in adults is estimated to be 70-99% worldwide. A large number of studies have demonstrated evidence of inflammation and immune activation, including HCMV-specific T-cell clonal expansion, in HCMV seropositive older adults, suggesting chronic HCMV infection may serve as a driving force for age-related immunosenescence. However, the relationship between positive anti-HCMV serology and adverse health outcomes in older adults, such as disability and frailty, remains controversial. Therefore, whether chronic HCMV infection is the culprit or an innocent bystander in immunosenescence, will require further investigation. Recent studies suggest that novel techniques such as HCMV DNA detection in peripheral blood monocytes by nested PCR may improve the diagnosis of chronic HCMV infection in older adults and help to address the above controversies. This chapter will provide an overview of our current understanding of HCMV infection and its risk factors, diagnosis, and impact on the immune system.