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.