Minimal immune determinants connect Zika virus, human Cytomegalovirus, and Toxoplasma gondii to microcephaly-related human proteins.

Aiming at the molecular definition of the relationship(s) between prenatal infections and fetal microcephaly and using pentapeptides as minimal immune determinants, we analyzed the peptide matching between proteins from infectious agents involved in microcephalic syndromes (namely Zika virus, human Cytomegalovirus, and Toxoplasma gondii) and human proteins that, when altered, have been specifically associated with microcephaly. We report that an unexpected high number of epitopic pentapeptides (ie, 34) are common to the three fetopathogenic agents and repeatedly occur throughout an important number of microcephaly-related human proteins. The data introduce the issue of multiple cross-reactivity into the etiology on ZIKV-associated pathologies. Indeed, the commonality of immune determinants might lead to a sequence of boostered immune responses if the host undergoes different fetopathogenic infections, thus temporally scanning a potential clinical progression toward brain malformations. At this juncture, the past history of maternal infections/vaccinations might dictate the fetal pathologic outcome.