Antiviral activity of human OASL protein is mediated by enhancing signaling of the RIG-I RNA sensor.

Abstract

Virus infection is sensed in the cytoplasm by retinoic acid-inducible gene I (RIG-I, also known as DDX58), which requires RNA and polyubiquitin binding to induce type I interferon (IFN) and activate cellular innate immunity. We show that the human IFN-inducible oligoadenylate synthetases-like (OASL) protein has antiviral activity and mediates RIG-I activation by mimicking polyubiquitin. Loss of OASL expression reduced RIG-I signaling and enhanced virus replication in human cells. Conversely, OASL expression suppressed replication of a number of viruses in a RIG-I-dependent manner and enhanced RIG-I-mediated IFN induction. OASL interacted and colocalized with RIG-I, and through its C-terminal ubiquitin-like domain specifically enhanced RIG-I signaling. Bone-marrow-derived macrophages from mice deficient for Oasl2 showed that among the two mouse orthologs of human OASL, Oasl2 is functionally similar to human OASL. Our findings show a mechanism by which human OASL contributes to host antiviral responses by enhancing RIG-I activation.

• Authors: Jianzhong Zhu, Yugen Zhang, Arundhati Ghosh, Rolando A Cuevas, Adriana Forero, Jayeeta Dhar, Mikkel Søes Ibsen, Jonathan Leo Schmid-Burgk, Tobias Schmidt, Madhavi K Ganapathiraju, Takashi Fujita, Rune Hartmann, Sailen Barik, Veit Hornung, Carolyn B Coyne, Saumendra N Sarkar
• Journal: Immunity (Immunity) Vol. 40 Issue 6 Pg. 936-48 (Jun 19 2014) ISSN: 1097-4180 [Electronic] United States
• PMID: 24931123 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• IRF7 protein, human
• Interferon Regulatory Factor-7
• Interferon Type I
• RNA, Small Interfering
• Receptors, Immunologic
• Polyubiquitin
• OASL protein, human
• Oasl2 protein, mouse
• 2',5'-Oligoadenylate Synthetase
• DDX58 protein, human
• DEAD Box Protein 58
• DEAD-box RNA Helicases

Topics

• 2',5'-Oligoadenylate Synthetase (genetics, immunology)
• Animals
• DEAD Box Protein 58
• DEAD-box RNA Helicases (immunology)
• DNA Virus Infections (immunology)
• HCT116 Cells
• HEK293 Cells
• Humans
• Immunity, Innate
• Interferon Regulatory Factor-7 (metabolism)
• Interferon Type I (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Polyubiquitin
• Protein Binding (immunology)
• RNA Interference
• RNA Virus Infections (immunology)
• RNA, Small Interfering
• Receptors, Immunologic
• Signal Transduction (immunology)
• Virus Replication (immunology)