Antiviral Activity of Human OASL Protein Is Mediated by Enhancing Signaling of the RIG-I RNA Sensor

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. Antiviral Activity of Human OASL Protein Is Mediated by Enhancing Signaling of the RIG-I RNA Sensor. Immunity. 2014 June 19; 40(6): 936–948.

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.

Publication Year: 
2014
Publication Credits: 
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. Coy
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