High-content screening of coronavirus genes for innate immune suppression revealsenhanced potency of SARS-CoV-2 proteins

Olson, E. J.; Brown, D. M.; Chang, T. Z.; Ding, L.; Ng, T. L.; Weiss, H. S.; Koch, P.; Koide, Y.; Rollins, N.; Mach, P.; Meisinger, T.; Bricken, T.; Rollins, J.; Zhang, Y.; Molloy, C.; Queenan, B. N.; Mitchison, T.; Marks, D.; Way, J. C.; Glass, J. I.; Silver, P. A.

doi:10.1101/2021.03.02.433434

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bioRxiv · 10.1101/2021.03.02.433434

High-content screening of coronavirus genes for innate immune suppression revealsenhanced potency of SARS-CoV-2 proteins

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Abstract

Suppression of the host intracellular innate immune system is an essential aspect of viral replication. Here, we developed a suite of medium-throughput high-content cell-based assays to reveal the effect of individual coronavirus proteins on antiviral innate immune pathways. Using these assays, we screened the 196 protein products of seven coronaviruses (SARS-CoV-2, SARS-CoV-1, 229E, NL63, OC43, HKU1 and MERS). This includes a previously unidentified gene in SARS-CoV-2 encoded within the Spike gene. We observe immune-suppressing activity in both known host-suppressing genes (e.g., NSP1, Orf6, NSP3, and NSP5) as well as other coronavirus genes, including the newly identified SARS-CoV-2 protein. Moreover, the genes encoded by SARS-CoV-2 are generally more potent immune suppressors than their homologues from the other coronaviruses. This suite of pathway-based and mechanism-agnostic assays could serve as the basis for rapid in vitro prediction of the pathogenicity of novel viruses based on provision of sequence information alone.

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Olson, E. J., Brown, D. M., Chang, T. Z., Ding, L., Ng, T. L., Weiss, H. S., Koch, P., Koide, Y., Rollins, N., Mach, P., Meisinger, T., Bricken, T., Rollins, J., Zhang, Y., Molloy, C., Queenan, B. N., Mitchison, T., Marks, D., Way, J. C., Glass, J. I., Silver, P. A.. 2021-03-02. High-content screening of coronavirus genes for innate immune suppression revealsenhanced potency of SARS-CoV-2 proteins. https://doi.org/10.1101/2021.03.02.433434

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