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Article ; Online: High-content screening of coronavirus genes for innate immune suppression reveals enhanced potency of SARS-CoV-2 proteins

Olson, Erika J / Brown, David M / Chang, Timothy Z / Ding, Lin / Ng, Tai L / Weiss, H. Sloane / Koch, Peter / Koide, Yukiye / Rollins, Nathan / Mach, Pia / Meisinger, Tobias / Bricken, Trenton / Rollins, Joshus / Zhang, Yun / Molloy, Colin / Queenan, Briodget N / Mitchison, Timothy / Marks, Debora / Way, Jeffrey C /
Glass, John I / Silver, Pamela A

bioRxiv

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 ... ...

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.
Keywords covid19
Language English
Publishing date 2021-03-02
Publisher Cold Spring Harbor Laboratory
Document type Article ; Online
DOI 10.1101/2021.03.02.433434
Database COVID19

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