Zika virus productively infects primary human placenta-specific macrophages

Abstract

The strong association of Zika virus infection with congenital defects has led to questions of how a flavivirus is capable of crossing the placental barrier to reach the fetal brain. Here, we demonstrate permissive Zika virus infection of primary human placental macrophages, commonly referred to as Hofbauer cells, and placental villous fibroblasts. We also demonstrate Zika virus infection of Hofbauer cells within the context of the tissue ex vivo using term placental villous explants. In addition to amplifying infectious virus within a usually inaccessible area, the putative migratory activities of Hofbauer cells may aid in dissemination of Zika virus to the fetal brain. Understanding the susceptibility of placenta-specific cell types will aid future work around and understanding of Zika virus–associated pregnancy complications.

Risks associated with viral infections during pregnancy

“…Of note, infection of the cytotrophoblast in early gestation was associated with loss of proliferation (138), which could contribute to ZIKV-associated miscarriage and growth restriction. Finally, this study found that placental fibroblasts and Hofbauer cells were infected by ZIKV (138), with similar findings reported by others (139). These cells are closely associated with the fetal vasculature and could be responsible for harboring virus that can be more easily transmitted to the fetus.…”

Screening Bioactives Reveals Nanchangmycin as a Broad Spectrum Antiviral Active against Zika Virus

“…Therefore, we utilized human primary uterine microvascular endothelial cells (UtMEC). Once ZIKV has breaches the placental barrier, it then targets cells types located in either the core of the villous trees of the human placenta such as placental fibroblasts (Jurado et al, 2016) and also likely targets fetal microvasculare cells to reach the fetal systemic circulation. Therefore, we also tested the effects of compounds in primary placental fibroblasts and in human umbilical vein endothelial cells (HUVEC).…”

Vulnerability of primitive human placental trophoblast to Zika virus

“…Additionally, damage to STB, for example, by herpes simplex virus (58), or transcytosis of ZIKV across STB by piggybacking on an Ig directed against another flavivirus, such as one of the DENV serotypes (18,59), could be other causes of fetal ZIKV infection beyond the first trimester and reasons for geographical and socioeconomic differences in fetal susceptibilities. Whole villi dissected from placentas at different stages of pregnancy and cultured in the presence of ZIKV certainly become infected (57,58,60,61), but STB remains largely unscathed. In the in vitro trophoblast system derived from term placenta, it also seems possible that infection Unlike trophoblast derived from term placentas, ESC differentiated under BAP conditions for 4 d, which we suggest is analogous to the primitive trophoblast of the early first trimester, are highly susceptible to infection by ZIKV U .…”