Zika Virus Infection at Different Pregnancy Stages: Anatomopathological Findings, Target Cells and Viral Persistence in Placental Tissues

Abstract

Zika virus (ZIKV) infection in humans has been associated with congenital malformations and other neurological disorders, such as Guillain-Barré syndrome. The mechanism(s) of ZIKV intrauterine transmission, the cell types involved, the most vulnerable period of pregnancy for severe outcomes from infection and other physiopathological aspects are not completely elucidated. In this study, we analyzed placental samples obtained at the time of delivery from a group of 24 women diagnosed with ZIKV infection during the first, second or third trimesters of pregnancy. Villous immaturity was the main histological finding in the placental tissues, although placentas without alterations were also frequently observed. Significant enhancement of the number of syncytial sprouts was observed in the placentas of women infected during the third trimester, indicating the development of placental abnormalities after ZIKV infection. Hyperplasia of Hofbauer cells (HCs) was also observed in these third-trimester placental tissues, and remarkably, HCs were the only ZIKV-positive fetal cells found in the placentas studied that persisted until birth, as revealed by immunohistochemical (IHC) analysis. Thirty-three percent of women infected during pregnancy delivered infants with congenital abnormalities, although no pattern correlating the gestational stage at infection, the IHC positivity of HCs in placental tissues and the presence of congenital malformations at birth was observed. Placental tissue analysis enabled us to confirm maternal ZIKV infection in cases where serum from the acute infection phase was not available, which reinforces the importance of this technique in identifying possible causal factors of birth defects. The results we observed in the samples from naturally infected pregnant women may contribute to the understanding of some aspects of the pathophysiology of ZIKV.

The role of pregnant women with rash in the Zika virus sentinel surveillance

“…The majority of confirmed cases of ZIKV occurred in the second and third trimesters of gestation. However, when analyzing the trimester of ZIKV infection in children born with microcephaly, we noticed that most of them became infected in the first trimester of pregnancy, which is compatible with the literature, since pregnant women with infection in the first trimester have the most severe cases, as well as an increased risk of microcephaly in their conceptuses 11,12,13 .…”

Maternal-Fetal Interplay in Zika Virus Infection and Adverse Perinatal Outcomes

“…More severe damage to fetal development, such as microcephaly, has been shown when maternal ZIKV infection occurs in the first trimester of pregnancy (141). Histopathological findings in the placenta at this time were similar to those found in TORCH infections, including chronic villitis, edema, trophoblastic lesion, and an increase in HBCs (142). However, third semester placentas showed only delayed villous maturation without any pathological changes.…”

Atovaquone Inhibits Arbovirus Replication through the Depletion of Intracellular Nucleotides

“…Finally, we show that atovaquone also works to inhibit ZIKV infection in human first-and second-trimester placental explants. Many studies have shown that placental cytotrophoblasts, trophoblasts, Hofbauer cells, and fibroblasts are susceptible to ZIKV (18,20,(70)(71)(72)(73)(74); thus, recreating the dynamics of this infection and host-virus interaction at the placental level makes this study relevant to the most vulnerable target of ZIKV, pregnant women.…”