Wnt3a Facilitates SARS-CoV-2 Pseudovirus Entry into Cells

• Published in: International journal of molecular sciences Vol. 25; no. 1; p. 217
• Main Authors: Melano, Ivonne, Chen, Hui-Jye, Ngwira, Loveness, Hsu, Pang-Hung, Kuo, Li-Lan, Noriega, Lloyd, Su, Wen-Chi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22.12.2023; MDPI
• Subjects: Analysis; Binding sites; canonical pathway; Coronaviruses; Cytoplasm; Cytotoxicity; Health aspects; host factor; Infection; Infections; Kinases; Ligands; Lungs; Maraviroc; Pandemics; Proteins; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Signal transduction; Transcription factors; Vaccines; virus entry; Viruses; Wnt3a; β-catenin; Taiwan; canonical pathway; ACE2; β-catenin; SARS-CoV-2; host factor; Wnt3a; virus entry
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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.