Neurological Consequences of CMV Infection: Overview of Pathogenesis and Host Responses

Human cytomegalovirus (CMV), a member of the Herpesviridae family, is a ubiquitous pathogen that causes mild or asymptomatic infection in healthy individuals but leads to severe complications in immunocompromised patients and congenitally infected newborns. CMV exhibits marked neurotropism, and infection of the central nervous system (CNS) can result in a broad spectrum of neurological manifestations, including encephalitis, cognitive impairment, and developmental anomalies such as microcephaly, cerebral palsy, and sensorineural hearing loss. Though the clinical importance of CMV on the nervous system is well known and studied, the molecular mechanisms underlying CMV neuropathogenesis remain incompletely understood. In this review we present current knowledge on CMV infection of the CNS, highlighting the viral and host determinants that influence neurotropism, latency, immune evasion, and neural injury. We discuss important molecular pathways involved in viral entry, replication, and host immune modulation that contribute to CNS pathology. The article summarises recent insights from in vitro and in vivo models elucidating how CMV interacts with cells of CNS to disrupt neurodevelopment and brain homoeostasis. Furthermore, we review the neurological manifestations of CMV with emphasis on long term neurological sequelae of congenital and acquired CMV infection, as well as characteristic radiological findings associated with CMV neuroinfection. Understanding the complex interplay between CMV and the host nervous system is essential for identifying therapeutic targets and developing effective preventive strategies. This review aims to provide a comprehensive overview of CMV neuropathogenesis and to identify critical knowledge gaps that can guide future research on CMV-associated neurological disease.