TY - JOUR
T1 - Antiviral Activity of Human OASL Protein Is Mediated by Enhancing Signaling of the RIG-I RNA Sensor
AU - Zhu, Jianzhong
AU - Zhang, Yugen
AU - Ghosh, Arundhati
AU - Cuevas, Rolando A.
AU - Forero, Adriana
AU - Dhar, Jayeeta
AU - Ibsen, MikkelSøes
AU - Schmid-Burgk, JonathanLeo
AU - Schmidt, Tobias
AU - Ganapathiraju, Madhavi K.
AU - Fujita, Takashi
AU - Hartmann, Rune
AU - Barik, Sailen
AU - Hornung, Veit
AU - Coyne, Carolyn B.
AU - Sarkar, Saumendra N.
PY - 2014/6/19
Y1 - 2014/6/19
N2 - 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-likedomain 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. © 2014 Elsevier Inc.
AB - 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-likedomain 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. © 2014 Elsevier Inc.
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U2 - 10.1016/j.immuni.2014.05.007
DO - 10.1016/j.immuni.2014.05.007
M3 - Article
C2 - 24931123
SN - 1074-7613
VL - 40
SP - 936
EP - 948
JO - Immunity
JF - Immunity
IS - 6
ER -
SDG 3 Good Health and Well-being