Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan.
International Master's Program of Biomedical Sciences, China Medical University, Taichung 404, Taiwan.
Int J Mol Sci. 2023 Dec 22;25(1):217. doi: 10.3390/ijms25010217.
How ACE2 functions as the major host receptor of SARS-CoV-2 despite having low expression in the lungs is still unknown. To facilitate the development of therapeutic strategies against coronaviruses, gaining a deeper comprehension of the molecular mechanism of SARS-CoV-2 infection is imperative. In our previous study, we identified several potential host factors of SARS-CoV-2 using an shRNA arrayed screen, one of which was Wnt3a. Here, we validated the significance of Wnt3a, a potent activator of the Wnt/β-catenin signaling pathway, for SARS-CoV-2 entry into cells by evaluating the effects of its knockdown and overexpression on SARS-CoV-2 pseudotyped virus entry. Further analysis revealed that SARS-CoV-2 pseudotyped virus infection activates the canonical Wnt/β-catenin signaling pathway, which we found could subsequently stimulate ACE2 transcription. Collectively, our study identified Wnt3a as an important host factor that facilitates ACE2-mediated virus infection. Insight into the virus entry mechanism is impactful as it will aid in developing novel therapeutic strategies against current and future coronavirus pandemics.
尽管 ACE2 在肺部的表达水平较低，但它如何作为 SARS-CoV-2 的主要宿主受体发挥作用仍不清楚。为了促进针对冠状病毒的治疗策略的发展，深入了解 SARS-CoV-2 感染的分子机制至关重要。在我们之前的研究中，我们使用 shRNA 阵列筛选鉴定了几种 SARS-CoV-2 的潜在宿主因子，其中之一是 Wnt3a。在这里，我们通过评估其敲低和过表达对 SARS-CoV-2 假型病毒进入的影响，验证了 Wnt3a（Wnt/β-连环蛋白信号通路的有效激活剂）对 SARS-CoV-2 进入细胞的重要性。进一步的分析表明，SARS-CoV-2 假型病毒感染激活了经典的 Wnt/β-连环蛋白信号通路，我们发现该通路随后可以刺激 ACE2 的转录。总之，我们的研究确定了 Wnt3a 是促进 ACE2 介导的病毒感染的重要宿主因子。深入了解病毒进入机制具有重要意义，因为它将有助于针对当前和未来的冠状病毒大流行开发新的治疗策略。
