Congenital Zika syndrome is associated with maternal protein malnutrition

BARBEITO-ANDRÉS, J.; PEZZUTO, P.; HIGA, L. M.; DIAS, A. A.; VASCONCELOS, J. M.; SANTOS, T. M. P.; FERREIRA, J. C. C. G.; FERREIRA, R. O.; DUTRA, F. F.; ROSSI, A. D.; BARBOSA, R. V.; AMORIM, C. K. N.; DE SOUZA, M. P. C.; CHIMELLI, L.; AGUIAR, R. S.; GONZALEZ, P. N.; LARA, F. A.; CASTRO, M. C.; MOLNÁR, Z.; LOPES, R. T.; BOZZA, M. T.; VIANEZ, J. L. S. G.; BARBEITO, C. G.; CUERVO, P.; BELLIO, M.; TANURI, A.; GARCEZ, P. P.

Science Advances

AAAS

Año: 2020 vol. 6

Zika virus (ZIKV) infection during pregnancy is associated with a spectrum of developmental impairments knownas congenital Zika syndrome (CZS). The prevalence of this syndrome varies across ZIKV endemic regions, suggestingthat its occurrence could depend on cofactors. Here, we evaluate the relevance of protein malnutrition for theemergence of CZS. Epidemiological data from the ZIKV outbreak in the Americas suggest a relationship betweenundernutrition and cases of microcephaly. To experimentally examine this relationship, we use immunocompetentpregnant mice, which were subjected to protein malnutrition and infected with a Brazilian ZIKV strain. We foundthat the combination of protein restriction and ZIKV infection leads to severe alterations of placental structure andembryonic body growth, with offspring displaying a reduction in neurogenesis and postnatal brain size. RNA-seqanalysis reveals gene expression deregulation required for brain development in infected low-protein progeny.These results suggest that maternal protein malnutrition increases susceptibility to CZS.