Cytomegalovirus Infection: The Neurodevelopmental Peptide Signatures

Abstract

Background and objective: HCMV infection may cause neurodevelopmental disorders, including intellectual disability, hearing loss, cortical malformations, and calcifications. Theorizing about the still unknown molecular basis of HCMV-related diseases, this study analyzes the peptide sharing between HCMV, strains AD169 and Merlin, and human proteins, searching for shared sequences that might lead to crossreactive autoimmune injuries in the brain during immune responses following HCMV infection.

Method: HCMV proteins were analyzed for peptides shared with the human proteome using the Pir Peptide Match resource.

Result: Numerous HCMV peptides (ranging from 9 to 13 mer in length) are disseminated through hundreds of human proteins. The peptide sharing mostly involves crucial neurodevelopmental antigens such as PITX3, implicated in the differentiation of meso-diencephalic dopaminergic neurons; SIX3, which controls proper anterioposterior patterning of the diencephalon and formation of the rostral diencephalon during forebrain development; and ZIC2, which plays a fundamental role in the early stage of organogenesis of the central nervous system.

Conclusion: This study describes a HCMV vs human peptide overlap that may represent a crossreactive platform linking the pathologic sequelae of HCMV infection to the immune anti-HCMV response. The data could inform development of effective and safe immune therapeutic/preventive approaches against HCMV infections.

Keywords: HCMV infection; HCMV-related diseases; anti-HCMV immune response; crossreactivity; neurodevelopmental proteins; peptide sharing..