Recent Updates on Research Models and Tools to Study Virus–Host Interactions at the Placenta

Abstract

The placenta is a unique mixed organ, composed of both maternal and fetal tissues, that is formed only during pregnancy and serves as the key physiological and immunological barrier preventing maternal–fetal transmission of pathogens. Several viruses can circumvent this physical barrier and enter the fetal compartment, resulting in miscarriage, preterm birth, and birth defects, including microcephaly. The mechanisms underlying viral strategies to evade the protective role of placenta are poorly understood. Here, we reviewed the role of trophoblasts and Hofbauer cells in the placenta and have highlighted characteristics of vertical and perinatal infections caused by a wide range of viruses. Moreover, we explored current progress and future opportunities in cellular targets, pathogenesis, and underlying biological mechanisms of congenital viral infections, as well as novel research models and tools to study the placenta.

Analysis of SARS-CoV-2 vertical transmission during pregnancy

“…As several lines of evidence indicate that systemic maternal infection and consequent inflammation contribute to the disruption of placenta development/function and possibly favour viral vertical transmission 43,44 , we decided to profile the inflammatory status of four selected patients at both local (placenta) and systemic (maternal and foetal) levels. The results obtained by different molecular approaches (RNA expression and protein secretion) give us the same take-home message by showing a trend of generalized immune activation in those patients (17 and 25), who were SARS-CoV-2 positive at delivery and, according to the viral-immunological analyses, infected their neonates in utero.…”

A Message from the Human Placenta: Structural and Immunomodulatory Defense against SARS-CoV-2

“…If pathogens break through this barrier, viral infections can result in detrimental defects, including miscarriage, stillbirth, fetal sepsis, premature delivery, fetal growth restriction, birth defects as microcephaly or congenital heart disease, as well as perinatal mortality [ 4 ]. Some of the most common pathogens that are able to cross and infect the placental barrier are referred to as TORCH ( T oxoplasma gondii , o thers (including varicella zoster virus, parvovirus B19, human immunodeficiency virus (HIV), enteroviruses, Listeria monocytogenes and Treponema pallidum causing syphilis), r ubella, c ytomegalovirus (CMV), and h erpes simplex virus (HSV)) [ 37 , 38 ].…”

“…In general, viral infections may predispose pregnancy towards preterm birth, which may have major long-term health implications for newborns [ 3 ]. Certain viral infections during pregnancy can lead to adverse pregnancy outcomes, like spontaneous abortion, mother-to-child transmission (vertical transmission) resulting in congenital viral syndromes, fetal growth restriction or stillbirth [ 4 ]. Overall, data from several maternal viral pneumonias, including influenza, varicella, rubella [ 5 , 6 ], SARS-CoV [ 7 ] and Middle East respiratory syndrome coronavirus (MERS-CoV) [ 8 ], suggest that pregnant women are more susceptible to SARS-CoV-2 infections resulting in adverse outcomes.…”

Coxsackievirus B3 Infection of Human Neural Progenitor Cells Results in Distinct Expression Patterns of Innate Immune Genes

“…Coxsackievirus B3 (CVB3) belongs to Enterovirus genus within the Picornaviridae family of viruses, associated with a wide variety of diseases, ranging from mild flu like symptoms to severe diseases including myocarditis, pancreatitis, and type I diabetes [1]. CVB3 can cause severe morbidity and mortality, particularly in younger patients, and infection during pregnancy can result in susceptibility to spontaneous abortion, fetal myocarditis, and neurodevelopmental defects in neonates [2,3]. In addition, the neonatal central nervous system (CNS) and heart are major targets of CVB3 infection.…”