During human pregnancy, CMV infects the uterine-placental interface with varied outcomes from fetal intrauterine growth restriction to permanent birth defects, depending on the level of maternal immunity and gestational age. Virus spreads from infected uterine blood vessels, amplifies by replicating in decidual cells, and disseminates to the placenta in immune complexes. Cytotrophoblasts – epithelial cells of the placenta – differentiate along two distinct pathways. In the first, cells fuse into syncytiotrophoblasts covering the surface of chorionic villi that transport substances from the maternal to fetal bloodstream. In the second, cells invade the uterine interstitium and blood vessels, remodel the vasculature and form anchoring villi. CMV initiates replication in cytotrophoblast progenitor cells of floating villi, whereas syncytiotrophoblasts are spared. This extraordinary pattern of focal infection in underlying cells hinges on virion receptors being upregulated as villous cytotrophoblasts begin to differentiate. Expression of developmentally regulated receptors could explain viral replication in spatially distinct maternal and fetal compartments. Reduced invasiveness of infected cells could impair remodeling of the uterine vasculature, restrict maternal blood flow and access of the fetus to nutrients causing intrauterine growth restriction.
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Pereira, L., Maidji, E. (2008). Cytomegalovirus Infection in the Human Placenta: Maternal Immunity and Developmentally Regulated Receptors on Trophoblasts Converge. In: Shenk, T.E., Stinski, M.F. (eds) Human Cytomegalovirus. Current Topics in Microbiology and Immunology, vol 325. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-77349-8_21
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