Analysis of the heterologous expression, localization, and cellular response to the Zika virus E protein in vitro.

Zika virus (ZIKV) infection has been associated with damage to neural stem cells in microcephaly in newborns. The virus possesses specific tropism for glioma stem cells mediated by the ZIKV E protein. This infection causes endoplasmic reticulum stress and activation of the unfolded protein response (UPR). However, the cellular response to the expression of the ZIKV E protein alone is unknown. Therefore, in this study, we determined the effect of the expression of the ZIKV E protein on cellular responses and its subcellular localization in HEK-293T cells, due to their use as a biotechnological tool for cellular and lentiviral therapy. We observed that the ZIKV E protein is synthesized in the cytoplasm and inserted into the endoplasmic reticulum (ER), without causing activation of the UPR or cell death, and it is finally transported and located in the cell membrane. Moreover, the expression of the ZIKV E protein does not induce UPR or apoptosis in glioma cells. These results help us to better understand the characteristics of this protein and its possible use as a biotechnological tool for the creation of different gene therapy strategies, vaccines, and synthetic vectors with tropism for neural and glioma stem cells.