Neuroteratogenic Viruses and Lessons for Zika Virus Models Kenneth Kim, Sujan Shresta  Trends in Microbiology  Volume 24, Issue 8, Pages 622-636 (August 2016) DOI: 10.1016/j.tim.2016.06.002 Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 1 Comparative Placentation of Primates, Mice, and Ruminants. (A) The primate placenta is hemomonochorial and composed of villi bathed in maternal blood and anchored in the uterine decidua. (B) The primate trophoblast–uterine interface is composed of extravillous trophoblasts (EVT) juxtaposed with decidual fibroblasts and maternal leukocytes. (C) In a cross-section of a primate placental villus, maternal blood is separated from fetal vessels by a single syncytiotrophoblast (SYN). Underlying the SYN is a layer of mononuclear subsyncytial trophoblasts (MNT) that loses continuity as gestation advances. Underlying both structures is a basement membrane (BM). (D) In the hemotrichorial mouse placenta, maternal and fetal vessels are in close contact within a nutrient-exchange labyrinth that is anchored in the decidua via a (E) Spongiotrophoblast (SpT) region and trophoblast giant cells (TGC, analogous to EVT). (F) Labyrinthine region cross-section. A semi-discontinuous layer of mononuclear trophoblasts (MNT) overlies two layers of syncytiotrophoblast. Beyond this lies fetal endothelium (FE). (G) The ruminant placenta is epitheliochorial, and composed of multiple placentomes throughout the uterus. (H) Each placentome includes a uterine caruncle and fetal cotyledon. (I) Much of the cotyledonary surface faces a maternal epithelium (Mepi). Maternal blood is separated from fetal blood (FB) by maternal endothelium (ME), endometrial fibroblasts, maternal epithelium, SYN, chorionic fibroblasts and fetal endothelium (FE). (B–I) Yellow cells, maternal leukocytes; spindle cells, fibroblasts. Figure from [7] with adapted description. Trends in Microbiology 2016 24, 622-636DOI: (10.1016/j.tim.2016.06.002) Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 2 Blood–Brain Barrier (BBB) Structure and Mechanisms of Viral Entry. Structures composing the normal BBB are astrocytes, basal lamina, pericytes, and endothelial cells joined by tight junctions. Hematogenous viruses gain entry into the central nervous system (CNS) by transcytosis through the endothelium, paracytosis through intercellular junctions, transport by phagocytes, and through a disrupted BBB. Other viruses can enter the CNS via axonal transport (not pictured). Trends in Microbiology 2016 24, 622-636DOI: (10.1016/j.tim.2016.06.002) Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 3 Superior Views of Normal Brain and Viral Neuroteratogenesis in Calves. (A) In normal brain the cerebral hemispheres (Cx) fill the cranial cavity, and prominent gyri and sulci are apparent on the brain's surface. (B) In this case transplacental infection with Akabane virus has led to near complete necrosis of the cerebral hemispheres, the thin hemispheres are collapsed, and the resulting space is mostly fluid-filled (hydranencephaly). Similar teratogenesis has resulted from live vaccine strains of Bluetongue virus. Abbreviation: Fl, fluid. (B) reproduced from [34]; (A) provided by J.S. Agerholm. Trends in Microbiology 2016 24, 622-636DOI: (10.1016/j.tim.2016.06.002) Copyright © 2016 Elsevier Ltd Terms and Conditions