Why certain viruses cross the physical barrier of the human placenta but others do not is incompletely understood. Over the past 20 years, we have gained deeper knowledge of intrauterine infection and routes of viral transmission. This review focuses on human viruses that replicate in the placenta, infect the fetus, and cause birth defects, including rubella virus, varicella-zoster virus, parvovirus B19, human cytomegalovirus (CMV), Zika virus (ZIKV), and hepatitis E virus type 1. Detailed discussions include (a) the architecture of the uterine-placental interface, (b) studies of placental explants ex vivo that provide insights into the infection and spread of CMV and ZIKV to the fetal compartment and how these viruses undermine early development, and (c) novel treatments and vaccines that limit viral replication and have the potential to reduce dissemination, vertical transmission and the occurrence of congenital disease.

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