PT  - JOURNAL ARTICLE
AU  - Olson, Erika J.
AU  - Brown, David M.
AU  - Chang, Timothy Z.
AU  - Ding, Lin
AU  - Ng, Tai L.
AU  - Weiss, H. Sloane
AU  - Koide, Yukiye
AU  - Koch, Peter
AU  - Rollins, Nathan
AU  - Mach, Pia
AU  - Meisinger, Tobias
AU  - Bricken, Trenton
AU  - Rollins, Joshua
AU  - Zhang, Yun
AU  - Molloy, Colin
AU  - Zhang, Yun
AU  - Queenan, Bridget N.
AU  - Mitchison, Timothy
AU  - Marks, Debora
AU  - Way, Jeffrey C.
AU  - Glass, John I.
AU  - Silver, Pamela A.
TI  - High-content screening of coronavirus genes for innate immune suppression reveals enhanced potency of SARS-CoV-2 proteins
AID  - 10.1101/2021.03.02.433434
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.03.02.433434
4099  - http://biorxiv.org/content/early/2021/03/02/2021.03.02.433434.short
4100  - http://biorxiv.org/content/early/2021/03/02/2021.03.02.433434.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.