Term Human Placental Trophoblasts Express SARS-CoV-2 Entry Factors ACE2, TMPRSS2, and Furin.
Term Human Placental Trophoblasts Express SARS-CoV-2 Entry Factors ACE2, TMPRSS2, and Furin.
复制标题
术语人胎盘滋养细胞表达SARS-COV-2进入因子ACE2，TMPRSS2和FURIN。
DOI：
10.1128/msphere.00250-21
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发表时间：
2021-04-14
期刊：
影响因子：
4.8
通讯作者：
Sadovsky Y
中科院分区：
文献类型：
--
作者：
Ouyang Y;Bagalkot T;Fitzgerald W;Sadovsky E;Chu T;Martínez-Marchal A;Brieño-Enríquez M;Su EJ;Margolis L;Sorkin A;Sadovsky Y
由严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）引起的2019年冠状病毒病（COVID-19）大流行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。由于胎盘滋养层细胞直接沐浴在母体血液中，它们对SARS-CoV-2很脆弱。有趣的是，人类胎儿在很大程度上免于SARS-CoV-2感染。我们检测了人胎盘是否表达主要的SARS-CoV-2进入因子血管紧张素转换酶2（ACE 2）、跨膜蛋白酶丝氨酸2（TMPRSS 2）和弗林蛋白酶，结果表明ACE 2和TMPRSS 2在滋养层细胞而不是其他胎盘绒毛细胞中表达。虽然弗林蛋白酶在主要的胎盘绒毛细胞类型中表达，我们调查，滋养层细胞表现出最高的表达。与这些进入因子的表达一致，我们证明了SARS-CoV-2假病毒可以进入原代人滋养层细胞。胎盘对SARS-CoV-2感染的防御机制可能涉及产后处理，这可能与减轻对SARS-CoV-2的干预密切相关。全球孕妇均受到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的胎儿-胎盘感染似乎是可能的。然而，尽管对孕妇的风险增加，但到目前为止，COVID-19传播到胎儿胎盘单位的风险似乎极低。这最近被归因于SARS-CoV-2进入因子在人胎盘中的可忽略表达。因此，我们试图探索进入因子ACE 2和TMPRSS 2在不同类型的人胎盘绒毛细胞中的表达。使用转录组测序（RNA-seq），实时定量PCR（RT-qPCR），原位杂交和免疫荧光的组合，我们发现滋养层细胞，但不是其他主要的绒毛细胞类型，表达ACE 2和TMPRSS 2，广泛表达弗林蛋白酶。相应地，我们也发现原代人滋养层细胞允许SARS-CoV-2假病毒颗粒进入。
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. IMPORTANCE 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), in situ 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.