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

Genome Biol. 2021 Oct 22;22(1):297. doi: 10.1186/s13059-021-02513-w.

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.

Keywords: CRISPR; Genome-wide screen; OLFML3; Rhinovirus; Surfaceome screen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CRISPR-Cas Systems*
  • Genome, Human
  • Glycoproteins / metabolism*
  • Glycoproteins / physiology
  • HeLa Cells
  • Humans
  • Immunity, Innate
  • Interferon Type I / antagonists & inhibitors*
  • Rhinovirus / physiology*
  • Signal Transduction
  • Suppressor of Cytokine Signaling 3 Protein / metabolism
  • rab5 GTP-Binding Proteins / physiology

Substances

  • Glycoproteins
  • Interferon Type I
  • OLFML3 protein, human
  • SOCS3 protein, human
  • Suppressor of Cytokine Signaling 3 Protein
  • RAB5C protein, human
  • rab5 GTP-Binding Proteins