Journal article
Combating viral contaminants in CHO cells by engineering innate immunity
University of California at San Diego1
United States Food and Drug Administration2
National Institutes of Health3
Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark4
CHO Core, Translational Management, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark5
Viral contamination in biopharmaceutical manufacturing can lead to shortages in the supply of critical therapeutics. To facilitate the protection of bioprocesses, we explored the basis for the susceptibility of CHO cells to RNA virus infection. Upon infection with certain ssRNA and dsRNA viruses, CHO cells fail to generate a significant interferon (IFN) response.
Nonetheless, the downstream machinery for generating IFN responses and its antiviral activity is intact in these cells: treatment of cells with exogenously-added type I IFN or poly I:C prior to infection limited the cytopathic effect from Vesicular stomatitis virus (VSV), Encephalomyocarditis virus (EMCV), and Reovirus-3 virus (Reo-3) in a STAT1-dependent manner.
To harness the intrinsic antiviral mechanism, we used RNA-Seq to identify two upstream repressors of STAT1: Gfi1 and Trim24. By knocking out these genes, the engineered CHO cells exhibited activation of cellular immune responses and increased resistance to the RNA viruses tested. Thus, omics-guided engineering of mammalian cell culture can be deployed to increase safety in biotherapeutic protein production among many other biomedical applications.
Language: | English |
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Publisher: | Nature Publishing Group UK |
Year: | 2019 |
Pages: | 8827 |
ISSN: | 20452322 |
Types: | Journal article |
DOI: | 10.1038/s41598-019-45126-x |
ORCIDs: | 0000-0002-0780-6096 , 0000-0001-8641-5706 , Petersen Bjørn, Sara and Voldborg, Bjørn Gunnar |
Animals Biomarkers CHO Cells Cellular signalling networks Cricetulus Drug Resistance Genetic Engineering Host-Pathogen Interactions Immunity, Innate Industrial Microbiology Interferon Type I Next-generation sequencing Poly I-C RNA Viruses STAT1 Transcription Factor Signal Transduction Virus Replication Virus-host interactions