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Surfaceome CRISPR screen identifies OLFML3 as a rhinovirus-inducible IFN antagonist.


ABSTRACT:

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.

SUBMITTER: Mei H 

PROVIDER: S-EPMC8532573 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Publications

Surfaceome CRISPR screen identifies OLFML3 as a rhinovirus-inducible IFN antagonist.

Mei Hong H   Zha Zhao Z   Wang Wei W   Xie Yusang Y   Huang Yuege Y   Li Wenping W   Wei Dong D   Zhang Xinxin X   Qu Jieming J   Liu Jia J  

Genome biology 20211022 1


<h4>Background</h4>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.<h4>Results</h4>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 fin  ...[more]

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