Congenital Zika syndrome is associated with maternal protein malnutrition.
Barbeito-Andrés J., Pezzuto P., Higa LM., Dias AA., Vasconcelos JM., Santos TMP., Ferreira JCCG., Ferreira RO., Dutra FF., Rossi AD., Barbosa RV., Amorim CKN., De Souza MPC., Chimelli L., Aguiar RS., Gonzalez PN., Lara FA., Castro MC., Molnár Z., Lopes RT., Bozza MT., Vianez JLSG., Barbeito CG., Cuervo P., Bellio M., Tanuri A., Garcez PP.
Zika virus (ZIKV) infection during pregnancy is associated with a spectrum of developmental impairments known as congenital Zika syndrome (CZS). The prevalence of this syndrome varies across ZIKV endemic regions, suggesting that its occurrence could depend on cofactors. Here, we evaluate the relevance of protein malnutrition for the emergence of CZS. Epidemiological data from the ZIKV outbreak in the Americas suggest a relationship between undernutrition and cases of microcephaly. To experimentally examine this relationship, we use immunocompetent pregnant mice, which were subjected to protein malnutrition and infected with a Brazilian ZIKV strain. We found that the combination of protein restriction and ZIKV infection leads to severe alterations of placental structure and embryonic body growth, with offspring displaying a reduction in neurogenesis and postnatal brain size. RNA-seq analysis reveals gene expression deregulation required for brain development in infected low-protein progeny. These results suggest that maternal protein malnutrition increases susceptibility to CZS.