Zika virus and the blood-brain barrier

The blood brain barrier is a complex network of junctions that preserves homeostasis of the central nervous system and confines diffusion of soluble molecules and immune cells from the systemic compartments of the body into the central nervous system. Unfortunately, the blood brain barrier is not impenetrable as evidenced by the multitude of viruses or other pathological circumstances that either lead to damage or breakdown of these junctional proteins. As a neurotropic flavivirus, Zika virus infection leads to neurological disorders such as Guillain-Barré syndrome in adults, it also causes congenital malformations such as microcephaly, calcifications of the central nervous system and ventriculomegaly in newborns through transplacental transmission from infected mothers to fetus during pregnancy. Disruption of the blood brain barrier is the event that occurs prior to viral entry into the central nervous system, causing impairment of fetal and maternal cells including neural stem cells, astrocytes, neural progenitor cells, microglia, Hofbauer cells, and endothelial cells. Endothelial dysfunction is normally identified as the cause of integrity disruption of blood brain barrier by flaviviruses and it has been reported that ZIKV penetration disrupt endothelial integrity, thus, compromising the blood brain barrier. This review discusses the mechanisms exploited by Zika virus for viral entry and crossing the blood brain barrier, as well as endothelial dysfunction reported in different flavivirus infections.