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

Ying Liu, Ning Lu, Bin Yuan, Leiyun Weng, Feng Wang, Yong Jun Liu, Zhiqiang Zhang

Research output: Contribution to journalArticle

30 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)49-57
Number of pages9
JournalCellular and Molecular Immunology
Volume11
Issue number1
DOIs
StatePublished - 2014

Keywords

  • DHX33
  • Helicase
  • Innate immunity
  • IPS-1
  • Myeloid dendritic cell
  • Viral nucleic acid

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

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