Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
mSphere. 2021 Apr 14;6(2):e00250-21. doi: 10.1128/mSphere.00250-21.
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a massive impact on human lives worldwide. While the airborne SARS-CoV-2 primarily affects the lungs, viremia is not uncommon. As placental trophoblasts are directly bathed in maternal blood, they are vulnerable to SARS-CoV-2. Intriguingly, the human fetus is largely spared from SARS-CoV-2 infection. We tested whether the human placenta expresses the main SARS-CoV-2 entry factors angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and furin and showed that ACE2 and TMPRSS2 are expressed in the trophoblast rather than in other placental villous cells. While furin is expressed in the main placental villous cell types, we surveyed, trophoblasts exhibit the highest expression. In line with the expression of these entry factors, we demonstrated that a SARS-CoV-2 pseudovirus could enter primary human trophoblasts. Mechanisms underlying placental defense against SARS-CoV-2 infection likely involve postentry processing, which may be germane for mitigating interventions against SARS-CoV-2. Pregnant women worldwide have been affected by COVID-19. As the virus is commonly spread to various organs via the bloodstream and because human placental trophoblasts are directly bathed in maternal blood, feto-placental infection by SARS-CoV-2 seems likely. However, despite the heightened risk to pregnant women, thus far the transmission risk of COVID-19 to the feto-placental unit seems extremely low. This has been recently attributed to a negligible expression of SARS-CoV-2 entry factors in the human placenta. We therefore sought to explore the expression of the entry factors ACE2 and TMPRSS2 in the different cell types of human placental villi. Using a combination of transcriptome sequencing (RNA-seq), real-time quantitative PCR (RT-qPCR), hybridization, and immunofluorescence, we found that trophoblasts, but not the other main villous cell types, express ACE2 and TMPRSS2, with a broad expression of furin. Correspondingly, we also showed that primary human trophoblasts are permissive to entry of SARS-CoV-2 pseudovirus particles.
新型冠状病毒病 2019（COVID-19）大流行是由严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）引起的，对全球人类生活产生了巨大影响。虽然空气传播的 SARS-CoV-2 主要影响肺部，但病毒血症并不罕见。由于胎盘滋养层直接浸泡在母体血液中，因此它们容易受到 SARS-CoV-2 的影响。有趣的是，人类胎儿在很大程度上免受 SARS-CoV-2 感染。我们测试了人类胎盘是否表达 SARS-CoV-2 的主要进入因素血管紧张素转换酶 2（ACE2）、跨膜蛋白酶丝氨酸 2（TMPRSS2）和弗林，并表明 ACE2 和 TMPRSS2 在滋养层中表达，而不在其他胎盘绒毛细胞中表达。虽然弗林在主要胎盘绒毛细胞类型中表达，但我们调查显示，滋养层表达最高。与这些进入因素的表达一致，我们证明了 SARS-CoV-2 假病毒可以进入原代人滋养层。胎盘防御 SARS-CoV-2 感染的机制可能涉及进入后的处理，这对于减轻针对 SARS-CoV-2 的干预措施可能很重要。全世界的孕妇都受到了 COVID-19 的影响。由于病毒通常通过血液传播到各种器官，并且由于人类胎盘滋养层直接浸泡在母体血液中，因此 SARS-CoV-2 似乎很可能感染胎儿-胎盘。然而，尽管孕妇面临更高的风险，但迄今为止，COVID-19 向胎儿-胎盘单位的传播风险似乎极低。这最近归因于 SARS-CoV-2 进入因素在人胎盘组织中的表达微不足道。因此，我们试图探索 ACE2 和 TMPRSS2 进入因子在人胎盘绒毛不同细胞类型中的表达。我们使用转录组测序（RNA-seq）、实时定量 PCR（RT-qPCR）、杂交和免疫荧光的组合，发现滋养层，但不是其他主要绒毛细胞类型，表达 ACE2 和 TMPRSS2，并且广泛表达弗林。相应地，我们还表明，原代人滋养层允许 SARS-CoV-2 假病毒颗粒进入。
