Purpose

The high infection rate of SARS-CoV-2 necessitates the need for multiple studies identifying the molecular mechanisms that facilitate the viral entry and propagation. Currently the potential extra-respiratory transmission routes of SARS-CoV-2 remain unclear.

Methods

Using single-cell RNA Seq and ATAC-Seq datasets and immunohistochemical analysis, we investigated SARS-CoV-2 tropism in the embryonic, fetal and adult human ocular surface.

Results

The co-expression of ACE2 receptor and entry protease TMPRSS2 was detected in the human adult conjunctival, limbal and corneal epithelium, but not in the embryonic and fetal ocular surface up to 21 post conception weeks. These expression patterns were corroborated by the single cell ATAC-Seq data, which revealed a permissive chromatin in ACE2 and TMPRSS2 loci in the adult conjunctival, limbal and corneal epithelium. Co-expression of ACE2 and TMPRSS2 was strongly detected in the superficial limbal, corneal and conjunctival epithelium, implicating these as target entry cells for SARS-CoV-2 in the ocular surface. Strikingly, we also identified the key pro-inflammatory signals TNF, NFKβ and IFNG as upstream regulators of the transcriptional profile of ACE2⁺TMPRSS2⁺ cells in the superficial conjunctival epithelium, suggesting that SARS-CoV-2 may utilise inflammatory driven upregulation of ACE2 and TMPRSS2 expression to enhance infection in ocular surface.

Conclusions

Together our data indicate that the human ocular surface epithelium provides an additional entry portal for SARS-CoV-2, which may exploit inflammatory driven upregulation of ACE2 and TMPRSS2 entry factors to enhance infection.

中文翻译：

---

SARS-CoV-2 进入基因在成人结膜、角膜缘和角膜上皮的共表达表明存在通过眼表的额外进入途径。

 目的

SARS-CoV-2 的高感染率需要进行多项研究来确定促进病毒进入和传播的分子机制。目前，SARS-CoV-2 潜在的呼吸道外传播途径仍不清楚。

 方法

使用单细胞 RNA Seq 和 ATAC-Seq 数据集以及免疫组织化学分析，我们研究了胚胎、胎儿和成人眼表中的 SARS-CoV-2 趋向性。

 结果

在受孕后 21 周内，在成人结膜、角膜缘和角膜上皮中检测到ACE2受体和进入蛋白酶TMPRSS2的共表达，但在胚胎和胎儿眼表面中未检测到。这些表达模式得到了单细胞 ATAC-Seq 数据的证实，该数据揭示了成人结膜、角膜缘和角膜上皮中ACE2和TMPRSS2基因座的允许染色质。在浅层角膜缘、角膜和结膜上皮中强烈检测到 ACE2 和 TMPRSS2 的共表达，表明这些细胞是眼表 SARS-CoV-2 的目标进入细胞。引人注目的是，我们还确定了关键的促炎信号 TNF、NFKβ 和 IFNG 作为表层结膜上皮中 ACE2 ⁺ TMPRSS2 ⁺细胞转录谱的上游调节因子，这表明 SARS-CoV-2 可能利用炎症驱动的ACE2和 TMPRSS2 + 细胞转录谱的上游调节因子。 TMPRSS2表达可增强眼表感染。

 结论

我们的数据共同表明，人类眼表上皮为 SARS-CoV-2 提供了额外的进入门户，这可能利用炎症驱动的ACE2和TMPRSS2进入因子的上调来增强感染。