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bioRxiv · 10.1101/2020.11.08.372607

Surfaceome CRISPR Screen Identifies OLFML3 as a Rhinovirus-inducible IFN Antagonist

Mei, H.·Zha, Z.·Wang, W.·Xie, Y.·Huang, Y.·Li, W.·Wei, D.·Zhang, X.·Xie, J.·Qu, M.·Liu, J.
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Abstract

BackgroundRhinoviruses (RVs) cause more than half of common cold and, in some cases, more severe diseases. Functional genomics analyses of RVs using siRNA or genome-wide CRISPR screen uncovered a limited set of host factors, few of which has proven clinical relevance. ResultsHerein, we systematically compared genome-wide CRISPR screen and surface protein-focused CRISPR screen, referred to as surfaceome CRISPR screen, for their efficiencies in identifying RV host factors. It was found that surfaceome screen outperformed genome-wide screen in the success rate of hit identification. Importantly, using surfaceome screen we have identified olfactomedin like 3 (OLFML3) as a novel host factor of RV serotypes A and B including a clinical isolate. We found that OLFML3 was a RV-inducible suppressor of the innate immune response and that OLFML3 antagonized type I interferon (IFN) signaling in a SOCS3-dependent manner. ConclusionOur study has suggested that RV-induced OLFML3expression is an important mechanism for RV to hijack the immune system and underscored surfaceome CRISPR screen in identifying viral host factors.

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Mei, H., Zha, Z., Wang, W., Xie, Y., Huang, Y., Li, W., Wei, D., Zhang, X., Xie, J., Qu, M., Liu, J.. 2020-11-08. Surfaceome CRISPR Screen Identifies OLFML3 as a Rhinovirus-inducible IFN Antagonist. https://doi.org/10.1101/2020.11.08.372607

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