Surfaceome CRISPR screen identifies OLFML3 as a rhinovirus-inducible IFN antagonist
H Mei, Z Zha, W Wang, Y Xie, Y Huang, W Li, D Wei… - Genome biology, 2021 - Springer
H Mei, Z Zha, W Wang, Y Xie, Y Huang, W Li, D Wei, X Zhang, J Qu, J Liu
Genome biology, 2021•SpringerAbstract Background Rhinoviruses (RVs) cause more than half of common colds 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 have
proven clinical relevance. Results Herein, we systematically compare genome-wide
CRISPR screen and surface protein-focused CRISPR screen, referred to as surfaceome
CRISPR screen, for their efficiencies in identifying RV host factors. We find that surfaceome …
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 have
proven clinical relevance. Results Herein, we systematically compare genome-wide
CRISPR screen and surface protein-focused CRISPR screen, referred to as surfaceome
CRISPR screen, for their efficiencies in identifying RV host factors. We find that surfaceome …
Background
Rhinoviruses (RVs) cause more than half of common colds 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 have proven clinical relevance.
Results
Herein, we systematically compare genome-wide CRISPR screen and surface protein-focused CRISPR screen, referred to as surfaceome CRISPR screen, for their efficiencies in identifying RV host factors. We find that surfaceome screen outperforms the genome-wide screen in the success rate of hit identification. Importantly, using the surfaceome screen, we identify olfactomedin-like 3 (OLFML3) as a novel host factor of RV serotypes A and B, including a clinical isolate. We find that OLFML3 is a RV-inducible suppressor of the innate immune response and that OLFML3 antagonizes type I interferon (IFN) signaling in a SOCS3-dependent manner.
Conclusion
Our study suggests that RV-induced OLFML3 expression is an important mechanism for RV to hijack the immune system and underscores surfaceome CRISPR screen in identifying viral host factors.
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