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Zinc-finger antiviral protein mediates RIG-I-like-receptor-independent antiviral response to murine leukemia virus

Hanna Lee1, 2, Jun Komano3, Tatsuya Saitoh1, 2 and Shizuo Akira1, 2*
  • 1 Osaka Unviresity, WPI Immunology frontier research center (IFReC), Japan
  • 2 Osaka University, Research Institute for Microbial Disease, Japan
  • 3 Osaka Prefectural Institue of Public Health, Department of Infection Disease, Japan

Innate immunity is induced after the recognition of viral RNAs by pattern-recognition receptors (PRRs) and is the first line of the host defenses against a variety of RNA viruses (1, 2). Although Toll-like receptor 7 (TLR7) recognizes the genomic RNA of extracellular murine leukemia virus (MLV) to mediate the antiviral response (3-5), the RNA-sensing PRR that recognizes the MLV in the cytosol is not fully understood. Here, we show that zinc-finger antiviral protein (ZAP) is a cytosolic viral RNA sensor, inducing the degradation of the MLV transcripts by the exosome, an RNA degradation system, on RNA granules. Although loss of the RIG-I-like receptors (RLRs), which recognize various RNA viruses in the cytosol and induce the type I interferon (IFN)-dependent antiviral response, does not alter the replication efficiency of MLV, loss of ZAP greatly enhances the replication efficiency of MLV. ZAP localizes to RNA granules, where the processing-body and stress-granule proteins assemble. The CCCH-type zinc-finger domains of ZAP, which are RNA-binding motifs, mediate its localization to the RNA granules. ZAP recruits the MLV transcripts and an exosome component to the RNA granules leading to degradation of MLV transcripts. Although ZAP was known as a regulator of RLR signaling in human cells (6), ZAP does not regulate the RLR-dependent production of type I IFN in mouse cells. Thus, ZAP is a novel member of the cytosolic viral RNA-sensing PRR family that induces elimination of RNA viruses independently of TLR and RLR family members.

Acknowledgements

We thank Drs. H. Fan, D. Trono, H. Miyoshi, and T. Taniguchi for providing invaluable materials. This work was supported by a Japan Society for the Promotion of Science Grant-in-Aid for Challenging Exploratory Research (to T.S.); the Cabinet Office, Government of Japan, and the Japan Society for the Promotion of Science Funding Program for World-Leading Innovative R&D on Science and Technology ‘FIRST Program’ (to S.A.); and National Institutes of Health Grant PO1-AI070167 (to S.A.).

References

1. Kawai T, Akira S (2009) The roles of TLRs, RLRs and NLRs in pathogen recognition. Int Immunol 21(4):317-337.
2. Iwasaki A (2012) A virological view of innate immune recognition. Annu Rev Microbiol 66:177-196.
3. Cella M, et al. (1999) Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nat Med 5(8):919-923.
4. Diebold SS, et al. (2004) Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 303(5663):1529-1531.
5. Heil F, et al. (2004) Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 303(5663):1526-1529.
6. Hayakawa S, et al. (2011) ZAPS is a potent stimulator of signaling mediated by the RNA helicase RIG-I during antiviral responses. Nat Immunol 12(1):37-44.

Keywords: Antiviral protein, innate immunity, Retrovirus, RNA granule, CCCH-type zinc-finger-domain-containing protein

Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.

Presentation Type: Abstract

Topic: Innate immunity

Citation: Lee H, Komano J, Saitoh T and Akira S (2013). Zinc-finger antiviral protein mediates RIG-I-like-receptor-independent antiviral response to murine leukemia virus. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00750

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Received: 18 Jun 2013; Published Online: 22 Aug 2013.

* Correspondence: Prof. Shizuo Akira, Osaka Unviresity, WPI Immunology frontier research center (IFReC), Osaka, Japan, sakira@biken.osaka-u.ac.jp