AI Article Synopsis
- Viral contamination in biopharmaceutical manufacturing can cause shortages of vital therapies, particularly affecting CHO cells' vulnerability to RNA viruses.
- CHO cells show a weak interferon response upon infection, but enhancing this response with treatments can reduce virus damage significantly.
- By using RNA sequencing to identify key genetic repressors, scientists engineered CHO cells to enhance their immune response, boosting protection against RNA viruses, which could improve biotherapeutic safety and efficacy.
Article Abstract
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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586939 | PMC |
| http://dx.doi.org/10.1038/s41598-019-45126-x | DOI Listing |
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