ArticleCell & bioscience2021
Deletion of ER-retention motif on SARS-CoV-2 spike protein reduces cell hybrid during cell-cell fusion.
Article in Cell & bioscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Establishment of replication-competent vesicular stomatitis virus recapitulating SADS-CoV entry.Journal of virology · 2024Article
- Mathematical Modeling of Virus-Mediated Syncytia Formation: Past Successes and Future Directions.Results and problems in cell differentiation · 2024Review
- Article
- Insights from the Construction of Adenovirus-Based Vaccine Candidates against SARS-CoV-2: Expecting the Unexpected.Viruses · 2023Article
- Article
- SARS-CoV-2 spike host cell surface exposure promoted by a COPI sorting inhibitor.Acta pharmaceutica Sinica. B · 2023Article
- Modified DNA vaccine confers improved humoral immune response and effective virus protection against SARS-CoV-2 delta variant.Scientific reports · 2022Article
- Estimation of virus-mediated cell fusion rate of SARS-CoV-2.Virology · 2022Article
- Hybrid/Atypical Forms of Circulating Tumor Cells: Current State of the Art.Biochemistry. Biokhimiia · 2022Review
- COVID-19: the CaMKII-like system of S protein drives membrane fusion and induces syncytial multinucleated giant cells.Immunologic research · 2021Article
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundThe novel SARS-CoV-2 has quickly become a global pandemic since the first reported case in December 2019, with the virus infecting millions of people to date. The spike (S) protein of the SARS-CoV-2 virus plays a key role in binding to angiotensin-converting enzyme 2 (ACE2), a host cell receptor for SARS-CoV-2. S proteins that are expressed on the cell membrane can initiate receptor-dependent syncytia formation that is associated with extensive tissue damage. Formation of syncytia have been previously observed in cells infected with various other viruses (e.g., HIV, Ebola, Influenza, and Herpesviruses). However, this phenomenon is not well documented and the mechanisms regulating the formation of the syncytia by SARS-CoV-2 are not fully understood.
resultsIn this study, we investigated the possibility that cell fusion events mediated by the S protein of SARS-CoV-2 and ACE2 interaction can occur in different human cell lines that mimic different tissue origins. These cell lines were transduced with either wild-type (WT-S) S protein or a mutated variant where the ER-retention motif was removed (Δ19-S), as well as human ACE2 expression vectors. Different co-culture combinations of spike-expressing 293T, A549, K562, and SK-Hep1 cells with hACE2-expressing cells revealed cell hybrid fusion. However, only certain cells expressing S protein can form syncytial structures as this phenomenon cannot be observed in all co-culture combinations. Thus, SARS-CoV-2 mediated cell-cell fusion represents a cell type-dependent process which might rely on a different set of parameters. Recently, the Δ19-S variant is being widely used to increase SARS-CoV-2 pseudovirus production for in vitro assays. Comparison of cell fusion occurring via Δ19-S expressing cells shows defective nuclear fusion and syncytia formation compared to WT-S.
conclusionsThis distinction between the Δ19-S variant and WT-S protein may have downstream implications for studies that utilize pseudovirus-based entry assays. Additionally, this study suggest that spike protein expressed by vaccines may affect different ACE2-expressing host cells after SARS-CoV-2 vaccine administration. The long-term effects of these vaccines should be monitored carefully. Δ19-S mRNA may represent a safer mRNA vaccine design in the future.
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