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Mol Cell. 2015 May 7;58(3):541-548. doi: 10.1016/j.molcel.2015.03.014. Epub 2015 Apr 16.

ATP-dependent effector-like functions of RIG-I-like receptors.

Author information

1
Program in Cellular and Molecular Medicine, Children's Hospital Boston, MA 02115, USA.
2
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences Nankai University, Tianjin 300071, China.
3
Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C The Rockefeller University, New York, New York 10065, USA.
4
Department of Biological Chemistry and Molecular Pharmacology Harvard Medical School, Boston, MA 02115, USA.
5
Institut für Molekulare Medizin, Universitätsklinikum Bonn, 53127 Bonn, Germany.
#
Contributed equally

Abstract

The vertebrate antiviral innate immune system is often considered to consist of two distinct groups of proteins: pattern recognition receptors (PRRs) that detect viral infection and induce the interferon (IFN) signaling, and effectors that directly act against viral replication. Accordingly, previous studies on PRRs, such as RIG-I and MDA5, have primarily focused on their functions in viral double-stranded RNA (dsRNA) detection and consequent antiviral signaling. We report here that both RIG-I and MDA5 efficiently displace viral proteins pre-bound to dsRNA in a manner dependent on their ATP hydrolysis, and that this activity assists a dsRNA-dependent antiviral effector protein, PKR, and allows RIG-I to promote MDA5 signaling. Furthermore, truncated RIG-I/MDA5 lacking the signaling domain, and hence the IFN stimulatory activity, displaces viral proteins and suppresses replication of certain viruses in an ATP-dependent manner. Thus, this study reveals novel "effector-like" functions of RIG-I and MDA5 that challenge the conventional view of PRRs.

PMID:
25891073
PMCID:
PMC4427555
DOI:
10.1016/j.molcel.2015.03.014
[Indexed for MEDLINE]
Free PMC Article

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