Congenital Zika syndrome is associated with maternal protein malnutrition.

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.

Zika virus impairs the development of blood vessels in a mouse model of congenital infection.

Zika virus (ZIKV) is associated with brain development abnormalities such as primary microcephaly, a severe reduction in brain growth. Here we demonstrated in vivo the impact of congenital ZIKV infection in blood vessel development, a crucial step in organogenesis. ZIKV was injected intravenously in the pregnant type 2 interferon (IFN)-deficient mouse at embryonic day (E) 12.5. The embryos were collected at E15.5 and postnatal day (P)2. Immunohistochemistry for cortical progenitors and neuronal markers at E15.5 showed the reduction of both populations as a result of ZIKV infection. Using confocal 3D imaging, we found that ZIKV infected brain sections displayed a reduction in the vasculature density and vessel branching compared to mocks at E15.5; altogether, cortical vessels presented a comparatively immature pattern in the infected tissue. These impaired vascular patterns were also apparent in the placenta and retina. Moreover, proteomic analysis has shown that angiogenesis proteins are deregulated in the infected brains compared to controls. At P2, the cortical size and brain weight were reduced in comparison to mock-infected animals. In sum, our results indicate that ZIKV impairs angiogenesis in addition to neurogenesis during development. The vasculature defects represent a limitation for general brain growth but also could regulate neurogenesis directly.

An ontogenetic approach to facial variation in three Native American populations.

Various explanations have been formulated regarding high levels of craniofacial variation among Native American populations but the contribution of developmental processes to the establishment of these patterns of variation remains unknown. In this study, we compare facial morphology in ontogenetic series of three Native South American populations, one hunter-gatherer group and two farmer groups, in order to test the null hypothesis that indicates that the pattern of facial differentiation between populations does not change during ontogeny. If diet-related factors contribute to outline facial morphology, it is likely to find greater differences between hunter-gatherer and both farmer groups than between two groups of farmers and this differentiation is expected to increase with age, especially in those structures that are influenced by the mechanical load of mastication. According to our results, hunter-gatherers clearly differ from the two groups of farmers. Non-heritable factors linked to diet, such as nutritional content of food, may increase differentiation across ontogeny in some cases. However, as hunter-gatherers were clearly separated from farmer populations during entire postnatal ontogeny, an important proportion of size variation may not necessarily reflect eco-sensitive changes. Consequently, the hypothesis cannot be completely rejected.