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The interaction between the helicase DHX33 and IPS-1 as a novel pathway to sense double-stranded RNA and RNA viruses in myeloid dendritic cells

Cellular & Molecular Immunology volume 11, pages 49–57 (2014)Cite this article

Abstract

In eukaryotes, there are at least 60 members of the DExD/H helicase family, many of which are able to sense viral nucleic acids. By screening all known family members, we identified the helicase DHX33 as a novel double-stranded RNA (dsRNA) sensor in myeloid dendritic cells (mDCs). The knockdown of DHX33 using small heteroduplex RNA (shRNA) blocked the ability of mDCs to produce type I interferon (IFN) in response to poly I:C and reovirus. The HELICc domain of DHX33 was shown to bind poly I:C. The interaction between DHX33 and IPS-1 is mediated by the HELICc region of DHX33 and the C-terminal domain of IPS-1 (also referred to MAVS and VISA). The inhibition of DHX33 expression by RNA interference blocked the poly I:C-induced activation of MAP kinases, NF-κB and IRF3. The interaction between the helicase DHX33 and IPS-1 was independent of RIG-I/MDA5 and may be a novel pathway for sensing poly I:C and RNA viruses in mDCs.

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Acknowledgements

We thank M Wentz for critical reading. We thank all of our colleagues in our laboratory.

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Author notes

  1. Dr YJ Liu, Baylor Institute for Immunology Research, Baylor Research Institute, 3434 Live Oak St, Dallas, TX 75204, USA. E-mail: yong-jun.liu@baylorhealth.edu

  2. Dr ZQ Zhang, Baylor Institute for Immunology Research, Baylor Research Institute, 3434 Live Oak St, Dallas, TX 75204, USA. E-mail: zhiqiang.zhang@baylorhealth.edu

Authors and Affiliations

  1. Department of Infectious Diseases, The First Hospital, Jilin University, Changchun, China

    Ying Liu & Feng Wang

  2. Department of Immunology, Center for Cancer Immunology Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Ning Lu & Bin Yuan

  3. Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX, USA

    Leiyun Weng, Yong-Jun Liu & Zhiqiang Zhang

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Liu, Y., Lu, N., Yuan, B. et al. The interaction between the helicase DHX33 and IPS-1 as a novel pathway to sense double-stranded RNA and RNA viruses in myeloid dendritic cells. Cell Mol Immunol 11, 49–57 (2014). https://doi.org/10.1038/cmi.2013.40

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