Combating viral contaminants in CHO cells by engineering innate immunity

Austin W.T. Chiang, Shangzhong Li, Benjamin P. Kellman, Gouri Chattopadhyay, Yaqin Zhang, Chih Chung Kuo, Jahir M. Gutierrez, Faezeh Ghazi, Hana Schmeisser, Patrice Ménard, Sara Petersen Bjørn, Bjørn Gunnar Voldborg, Amy S. Rosenberg, Montserrat Puig*, Nathan E. Lewis

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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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.
Original languageEnglish
Article number8827
JournalScientific Reports
Volume9
Issue number1
ISSN2045-2322
DOIs
Publication statusPublished - 2019

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