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Identification of cell lines CL-14, CL-40 and CAL-51 as suitable models for SARS-CoV-2 infection studies
Claudia Pommerenke1, Ulfert Rand2, Cord C Uphoff3
1Department of Bioinformatics and Databases, Leibniz Institute DSMZ - German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany.
Abstract:
The SARS-CoV-2 pandemic is a major global threat that sparked global research efforts. Pre-clinical and biochemical SARS-CoV-2 studies firstly rely on cell culture experiments where the importance of choosing an appropriate cell culture model is often underestimated. We here present a bottom-up approach to identify suitable permissive cancer cell lines for drug screening and virus research. Human cancer cell lines were screened for the SARS-CoV-2 cellular entry factors ACE2 and TMPRSS2 based on RNA-seq data of the Cancer Cell Line Encyclopedia (CCLE). However, experimentally testing permissiveness towards SARS-CoV-2 infection, we found limited correlation between receptor expression and permissiveness. This underlines that permissiveness of cells towards viral infection is determined not only by the presence of entry receptors but is defined by the availability of cellular resources, intrinsic immunity, and apoptosis. Aside from established cell culture infection models CACO-2 and CALU-3, three highly permissive human cell lines, colon cancer cell lines CL-14 and CL-40 and the breast cancer cell line CAL-51 and several low permissive cell lines were identified. Cell lines were characterised in more detail offering a broader choice of non-overexpression in vitro infection models to the scientific community. For some cell lines a truncated ACE2 mRNA and missense variants in TMPRSS2 might hint at disturbed host susceptibility towards viral entry.
Insights
Identifying suitable cell culture models is crucial for SARS-CoV-2 research. This study found that cancer cell permissiveness to SARS-CoV-2 depends on more than just entry receptors, identifying new models for drug screening.
Area of Science:
- Virology
- Cell Biology
- Cancer Research
Background:
- The SARS-CoV-2 pandemic necessitates robust preclinical research, heavily relying on cell culture models.
- Selecting appropriate cell lines is critical but often underestimated, impacting study reliability.
Purpose of the Study:
- To develop a systematic approach for identifying permissive cancer cell lines for SARS-CoV-2 drug screening and research.
- To evaluate the correlation between cellular entry factor expression and actual viral permissiveness.
Main Methods:
- Screened human cancer cell lines from the Cancer Cell Line Encyclopedia (CCLE) for ACE2 and TMPRSS2 expression using RNA-seq data.
- Experimentally validated SARS-CoV-2 permissiveness in selected cell lines.
- Characterized identified cell lines for broader applicability.
Main Results:
- Limited correlation observed between ACE2/TMPRSS2 expression and SARS-CoV-2 permissiveness, indicating other cellular factors are involved.
- Identified three highly permissive cancer cell lines (CL-14, CL-40, CAL-51) beyond established models (CACO-2, CALU-3).
- Identified several low-permissive cell lines, expanding the options for in vitro infection models.
Conclusions:
- Cellular permissiveness to SARS-CoV-2 is multifactorial, influenced by entry receptors, cellular resources, intrinsic immunity, and apoptosis.
- The study provides a valuable resource of diverse, non-overexpressing cell lines for SARS-CoV-2 research and drug discovery.
- Potential genetic factors like truncated ACE2 mRNA and TMPRSS2 variants may affect host susceptibility.
