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Cell Mol Immunol. 2014 Jan;11(1):49-57. doi: 10.1038/cmi.2013.40. Epub 2013 Sep 16.

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.

Author information

1
Department of Infectious Diseases, The First Hospital, Jilin University, Changchun, China.
2
Department of Immunology, Center for Cancer Immunology Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
3
Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX, USA.

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.

PMID:
24037184
PMCID:
PMC4002151
DOI:
10.1038/cmi.2013.40
[Indexed for MEDLINE]
Free PMC Article

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