Neuroteratogenic Viruses and Lessons for Zika Virus Models

The Centers for Disease Control and Prevention has confirmed that Zika virus (ZIKV) causes congenital microcephaly. ZIKV now joins five other neuroteratogenic (NT) viruses in humans and ZIKV research is in its infancy. In addition, there is only one other NT human arbovirus (Venezuelan equine encephalitis virus), which is also poorly understood. But further insight into ZIKV can be found by evaluating arboviruses in domestic animals, of which there are at least seven NT viruses, three of which have been well studied. Here we review two key anatomical structures involved in modeling transplacental NT virus transmission: the placenta and the fetal blood–brain barrier. We then survey major research findings regarding transmission of NT viruses for guidance in establishing a mouse model of Zika disease that is crucial for a better understanding of ZIKV transmission and pathogenesis.

TrendsA substantial body of scientific information exists on transplacental transmission (TPT) of naturally occurring neuroteratogenic (NT) viruses, including mouse models of Japanese encephalitis virus TPT.An ideal mouse model of Zika viral disease will demonstrate vector and sexual transmission, TPT, and productive infection of the fetal brain in a maximally immunocompetent host. Microcephaly is a nonspecific defect seen in many viral and noninfectious diseases.Each virus and host has a gestational teratogenic window of time during which infection of the brain can result in birth defects.To infect the fetal brain, viruses must breach the placenta and fetal blood–brain barrier.Potential target cells in the brain are stem/progenitor cells, neurons, oligodendrocytes, astrocytes, microglia, and endothelial cells.