Wnt3a Facilitates SARS-CoV-2 Pseudovirus Entry into Cells

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...

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Published inInternational 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
LanguageEnglish
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
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Abstract 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.
AbstractList 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.
Audience Academic
Author Noriega, Lloyd
Hsu, Pang-Hung
Kuo, Li-Lan
Ngwira, Loveness
Su, Wen-Chi
Melano, Ivonne
Chen, Hui-Jye
AuthorAffiliation 1 Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan; ivonnemelano@yahoo.com (I.M.); huijyechen@mail.cmu.edu.tw (H.-J.C.); ab801017@gmail.com (L.-L.K.); lloydnoriega@gmail.com (L.N.)
5 Institute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
2 International Master’s Program of Biomedical Sciences, China Medical University, Taichung 404, Taiwan; tiongengwira96@gmail.com
7 Drug Development Center, China Medical University, Taichung 404, Taiwan
3 Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202, Taiwan; phsu@ntou.edu.tw
6 Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan
4 Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung 202, Taiwan
AuthorAffiliation_xml – name: 3 Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202, Taiwan; phsu@ntou.edu.tw
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Issue 1
Keywords canonical pathway
ACE2
β-catenin
SARS-CoV-2
host factor
Wnt3a
virus entry
Language English
License https://creativecommons.org/licenses/by/4.0
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These authors contributed equally to this work.
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Snippet 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...
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SubjectTerms 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
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Title Wnt3a Facilitates SARS-CoV-2 Pseudovirus Entry into Cells
URI https://www.ncbi.nlm.nih.gov/pubmed/38203386
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https://pubmed.ncbi.nlm.nih.gov/PMC10778646
https://doaj.org/article/4bfa91baa95e424ca0effda21031b959
Volume 25
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