Yoshida Nagisa, Thomas Jake R, Appios Anna, Brember Matthew P, Aye Irving L M H, Edgar James R, Firth Andrew E, Chung Betty Y W, McGovern Naomi, Stewart Hazel
Department of Pathology, University of Cambridge, Cambridge, England, UK.
Centre for Trophoblast Research, University of Cambridge, Cambridge, England, UK.
Wellcome Open Res. 2024 Nov 22;9:209. doi: 10.12688/wellcomeopenres.20514.2. eCollection 2024.
Infection during pregnancy with SARS-CoV-2 can have a serious impact on both maternal and foetal health. Clinical studies have shown that SARS-CoV-2 transmission from the mother to the foetus typically does not occur. However, there is evidence that SARS-CoV-2 can infect the placenta . Here we sought to quantify the permissiveness of placental cells to SARS-CoV-2 infection and to determine if they support viral release.
By using publicly available single-cell RNA sequencing (scRNAseq) data sets and confocal microscopy we compared ACE2 transcript and protein expression across human first trimester and term placental cells. We also used infection assays to quantify the infection rates of a range of placenta-derived cells. Finally, we quantified the viral egress from these cells.
ACE2 transcripts are found in a range of placental cell types across gestation, including trophoblast. However, ACE2 protein expression does not significantly change across placental cell types from first trimester to term. We find that 0.5±0.15 % of term trophoblast cells can be infected with SARS-CoV-2 while primary placental fibroblasts and macrophages, and JEG-3, JAR and HUVEC cell lines are resistant to infection. Furthermore, primary trophoblast cells poorly support viral release while JEG-3 cells allow relatively high levels of viral release.
The low level of viral release by primary placental cells provides insight into how the virus is impaired from crossing the placenta to the foetus.
孕期感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）可对母婴健康产生严重影响。临床研究表明，SARS-CoV-2通常不会从母亲传播给胎儿。然而，有证据表明SARS-CoV-2可感染胎盘。在此，我们试图量化胎盘细胞对SARS-CoV-2感染的易感性，并确定它们是否支持病毒释放。
通过使用公开可用的单细胞RNA测序（scRNAseq）数据集和共聚焦显微镜，我们比较了人类孕早期和足月胎盘细胞中血管紧张素转换酶2（ACE2）转录本和蛋白的表达。我们还使用感染试验来量化一系列胎盘来源细胞的感染率。最后，我们量化了这些细胞的病毒释放。
在整个孕期的一系列胎盘细胞类型中都发现了ACE2转录本，包括滋养层细胞。然而，从孕早期到足月，ACE2蛋白表达在胎盘细胞类型之间没有显著变化。我们发现，0.5±0.15%的足月滋养层细胞可被SARS-CoV-2感染，而原代胎盘成纤维细胞和巨噬细胞以及JEG-3、JAR和人脐静脉内皮细胞（HUVEC）细胞系对感染具有抗性。此外，原代滋养层细胞对病毒释放的支持较差，而JEG-3细胞允许相对高水平的病毒释放。
原代胎盘细胞的低水平病毒释放为病毒如何在从胎盘传播到胎儿的过程中受到损害提供了见解。
