Wnt3a Facilitates SARS-CoV-2 Pseudovirus Entry into Cells
- Int J Mol Sci. 2023 Dec 22;25(1):217. doi: 10.3390/ijms25010217.
- 1. Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan.
- 2. International Master's Program of Biomedical Sciences, China Medical University, Taichung 404, Taiwan.
- 3. Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202, Taiwan.
- 4. Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung 202, Taiwan.
- 5. Institute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
- 6. Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan.
- 7. Drug Development Center, China Medical University, Taichung 404, Taiwan.
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.