Congenital Zika Syndrome is associated with maternal genetic background

Maternal and/or fetal factors that influence Congenital Zika Syndrome (CZS) development remain elusive. Interferon lambda has been reported as an antiviral factor in Zika infections. Using functional analysis, we conducted a case-control study to demonstrate that maternal interferon lambda single nucleotide polymorphisms (SNPs) contribute to newborn protection. Mothers carrying CA/CC genotypes of rs8109886 SNP have 4.5 times reduced risk of having children with CZS. When we combined the genotypes CC from rs12979860 and CA/CC from rs8109886, 93% of the mothers delivered healthy newborns. Placenta coming from CZS cases displayed diminished level of IFNL2 along with higher tissue-specific type-I IFN genes, tagged by of IFIT5, indicating that lower IFNL levels upon ZIKV infection can lead to uncontrolled damage to overexpression of type-I IFN pathway. In summary, genetically regulated IFNL levels contribute to immune homeostasis and CZS prevention.