Cytomegalovirus Infection and Neurological Disorders

Cytomegalovirus

Cytomegalovirus (CMV) is one of the eight human herpesviruses, classified as a β-herpesvirus due to its restricted host range. It is the leading non-genetic aetiology of congenital malformation in developed countries, causing significant fetal neurological injury, including microcephaly, intracranial calcifications, cerebral palsy, mental disability, sensorineural hearing loss, seizures, and visual impairment. CMV infection has not yet fully elucidated pathogenetic mechanisms for central nervous system damage.

In recent years, researchers have been investigating CMV-induced changes using multicellular cerebral organoids to demonstrate CMV-induced changes and interrogate the accompanying mRNA and protein expression. Cerebral organoids are three-dimensional structures that recapitulate brain development and provide a platform to study the effects of CMV infection on human brain development.

According to a study published in the journal Nature, human cytomegalovirus (HCMV) infection was found to dysregulate 236 Autism Spectrum Disorder (ASD)-related genes and pathways, suggesting a potential link between congenital CMV infection and ASD. Additionally, the study identified over-representation of 103 diseases related to neural malformation or mental disorders in CMV-infected organoids, suggesting potential mechanisms for congenital CMV-induced neural malformation and ASD.

The study also analyzed the effects of CMV infection on neuronal populations, revealing a reduction in neuronal populations in the fetal brain. This reduction was corroborated by gene ontology analysis, which showed significant CMV-induced over-representation of downregulated DEGs in systems involved in cellular differentiation and development.

The researchers demonstrated that CMV infection may acutely induce neurodegenerative disease-like pathology through a decrease in neuronal populations. They found significant alteration of protein localization for specific genes like DYRK1A, DYRK1B, ULK3, GLI2, Shh, and Rb (effector) in CMV-infected cerebral organoids, consistent with previous observations in HFF cells.

Another study published in the Journal of Virology indicated that CMV generates an assembly compartment (AC) in the early phase of infection, which is a large cytoplasmic structure containing a large number of membranous intermediates that may serve as a site for final CMV envelopment. The AC is fully formed at late stages of infection after late viral genes encoding tegument and envelope proteins are expressed.

In summary, CMV infection has been found to cause significant neurological injury in the fetal brain, including microcephaly, intracranial calcifications, cerebral palsy, mental disability, sensorineural hearing loss, seizures, and visual impairment. The pathogenetic mechanisms of CMV-induced central nervous system damage are not yet fully understood but may involve dysregulation of functions involving neurodegenerative diseases and disrupted neuronal differentiation.