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Congenital Zika syndrome is associated with maternal protein malnutrition

2020; American Association for the Advancement of Science; Volume: 6; Issue: 2 Linguagem: Inglês

10.1126/sciadv.aaw6284

2375-2548

Jimena Barbeito‐Andrés, Paula Pezzuto, Luiza M. Higa, André Alves Dias, Janaína Mota de Vasconcelos, Thaís Maria Pires dos Santos, Jéssica C. C. G. Ferreira, Raiane Oliveira Ferreira, Fabiano Ferreira, Átila Duque Rossi, Rudyan Victor Macêdo Barbosa, C. K. N. Amorim, Michel Platini Caldas de Souza, Leila Chimelli, Renato Santana Aguiar, Paula González, Flávio Alves Lara, Márcia C. Castro, Zoltàn Molnàr, Ricardo Tadeu Lopes, Marcelo T. Bozza, João Lídio da Silva Gonçalves Vianez Júnior, Cláudio Gustavo Barbeito, Patrícia Cuervo, Maria Bellio, Amílcar Tanuri, Patrícia P. Garcez,

Child Nutrition and Water Access

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.