About: Screening and testing for a suitable untransfected cell line for SARS-CoV-2 studies

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About: Screening and testing for a suitable untransfected cell line for SARS-CoV-2 studies Goto Sponge NotDistinct Permalink

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Screening and testing for a suitable untransfected cell line for SARS-CoV-2 studies
Creator	Ludwig, Stephan Riese, Peggy Brunotte, Linda Eschke, Kathrin Cicin-Sain, Luka Denkmann, Sabine Hauer, Vivian Kaufmann, Maren Kim, Yeonsu Kurolt, Ivan-Christian Markotic, Alemka Meyer, Corinna Nagel, Stefan Pommerenke, Claudia Rand, Ulfert Safranko, Zeljka Steenpaß, Laura Uphoff, Cord Zaborski, Margarete
Source	BioRxiv
abstract	At present, the novel pandemic coronavirus SARS-CoV-2 is a major global threat to human health and hence demands united research activities at different levels. Finding appropriate cell systems for drug screening and testing molecular interactions of the virus with the host cell is mandatory for drug development and understanding the mechanisms of viral entry and replication. For this, we selected human cell lines represented in the Cancer Cell Line Encyclopedia (CCLE) based on RNA-seq data determined transcript levels of ACE2 and TMPRSS2, two membrane proteins that have been identified to aid SARS-CoV-2 entry into the host cell. mRNA and protein expression of these host factors were verified via RQ-PCR and western blot. We then tested permissiveness of these cell lines towards SARS-CoV-2 infection, cytopathic effect, and viral replication finding limited correlation between receptor expression and infectability. One of the candidate cancer cell lines, the human colon cancer cell line CL-14, tested positive for SARS-CoV-2 infection. Our data argue that SARS-CoV-2 in vitro infection models need careful selection and validation since ACE2/TMPRSS2 receptor expression on its own does not guarantee permissiveness to the virus. Author summary In the midst of the pandemic outbreak of corona-virus SARS-CoV-2 therapeutics for disease treatment are still to be tested and the virus-host-interactions are to be elucidated. Drug testing and viral studies are commonly conducted with genetically manipulated cells. In order to find a cell model system without genetic modification we screened human cell lines for two proteins known to facilitate entry of SARS-CoV-2. We confirmed and quantified permissiveness of current cell line infection models, but dismissed a number of receptor-positive cell lines that did not support viral replication. Importantly, ACE2/TMPRSS2 co-expression seems to be necessary for viral entry but is not sufficient to predict permissiveness of various cancer cell lines. Moreover, the expression of specific splice variants and the absence of missense mutations of the host factors might hint on successful infection and virus replication of the cell lines.
has issue date	2020-07-09(xsd:dateTime)
bibo:doi	10.1101/2020.07.09.195040
has license	biorxiv
sha1sum (hex)	eea620b16bbb47164304bbb1766c0ad8f433930b
schema:url	https://doi.org/10.1101/2020.07.09.195040
resource representing a document's title	Screening and testing for a suitable untransfected cell line for SARS-CoV-2 studies
schema:publication	bioRxiv
resource representing a document's body	covid:eea620b16bbb47164304bbb1766c0ad8f433930b#body_text
is schema:about of	named entity 'cell' named entity 'selected' named entity 'colon' named entity 'selection' named entity 'VIRAL ENTRY' named entity 'ONE OF' named entity 'VIRAL REPLICATION' named entity 'CYTOPATHIC EFFECT' named entity 'THREAT' named entity 'PANDEMIC' named entity 'PERMISSIVENESS' named entity 'DATA' named entity 'REPLICATION' named entity 'IS A' covid:arg/eea620b16bbb47164304bbb1766c0ad8f433930b named entity 'identified' named entity 'human health' named entity 'viral entry' named entity 'For' named entity 'virus' named entity 'positive' named entity 'cancer cell' named entity 'validation' named entity 'drug screening' named entity 'argue' named entity 'verified' named entity 'infection' named entity 'SARS-CoV-2' named entity 'SARS-CoV-2' named entity 'Cell Line' named entity 'coronavirus' named entity 'drug development' named entity 'virus' named entity 'ACE2' named entity 'molecular interactions' named entity 'SARS-CoV-2' named entity 'SARS-CoV-2' named entity 'western blot' named entity 'receptor expression' named entity 'scientific community' named entity 'antibiotics' named entity 'model systems' named entity 'human cell lines' named entity 'human cell lines' named entity 'breast carcinoma' named entity 'yeast' named entity 'squamous cell carcinoma' named entity 'Leibniz Institute DSMZ' named entity 'kidney' named entity 'serine protease' named entity 'vaccines' named entity 'Ensembl' named entity 'Calu-3' named entity 'epithelial cells' named entity 'DSMZ' named entity 'Vero E6' named entity 'virus replication' named entity 'KYSE' named entity 'mRNA' named entity 'ACE2' named entity 'mycoplasmas' named entity 'clinically proven' named entity 'cell types' named entity 'model systems' named entity 'mucosa' named entity 'TMPRSS2'

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