Proteome analysis of neural stem cells and neurospheres infected with Zika Virus

Abstract

The Brazilian outbreak of the Zika virus (ZIKV) in 2015 was accompanied by an increase in the number of cases of microcephaly, which involves severe changes in brain development, indicating a possible association between the viral infection with these cerebral malformations. The molecular mechanisms that promote these modifications have not been fully understood. In order to do so, in vitro models using human induced pluripotency stem cells (hiPSC), differentiated into neural cells, are being studied as a model of neurodevelopment. Here, we infected human neural progenitors (hNPCs) with ZIKV and dengue virus (DENV) strains. The infection was performed in the progenitor state and during its differentiation into neurospheres, in order to analyze in vitro the modifications caused by viral infection in these models. The samples, infected or not with one virus strain, underwent large-scale quantitative proteomic analysis, aiming to analyze differences and similarities of the effects of the Brazilian and African viral strains, as well as to compare ZIKV infection with DENV. The analysis of the cellular proteome allowed the identification of possible metabolic pathways and proteins, such as processing and splicing of mRNAs, Hippo, NIK/NF~kappaB and Wnt signaling pathways. Which may be related to the mechanisms and development of the disease. And we were also able to point potential differences between the cellular response to the different virus strains analyzed.