DDX1, DDX21, and DHX36 helicases form a complex with the adaptor molecule TRIF to sense dsRNA in dendritic cells. Academic Article uri icon

Overview

abstract

  • The innate immune system detects viral infection predominantly by sensing viral nucleic acids. We report the identification of a viral sensor, consisting of RNA helicases DDX1, DDX21, and DHX36, and the adaptor molecule TRIF, by isolation and sequencing of poly I:C-binding proteins in myeloid dendritic cells (mDCs). Knockdown of each helicase or TRIF by shRNA blocked the ability of mDCs to mount type I interferon (IFN) and cytokine responses to poly I:C, influenza A virus, and reovirus. Although DDX1 bound poly I:C via its Helicase A domain, DHX36 and DDX21 bound the TIR domain of TRIF via their HA2-DUF and PRK domains, respectively. This sensor was localized within the cytosol, independent of the endosomes. Thus, the DDX1-DDX21-DHX36 complex represents a dsRNA sensor that uses the TRIF pathway to activate type I IFN responses in the cytosol of mDCs.

authors

  • Zhang, Zhiqiang
  • Kim, Taeil
  • Bao, Musheng
  • Facchinetti, Valeria
  • Jung, Sung Yun
  • Ghaffari, Amir Ali
  • Qin, Jun
  • Cheng, Genhong
  • Liu, Yong-Jun

publication date

  • June 24, 2011

Research

keywords

  • Adaptor Proteins, Vesicular Transport
  • DEAD-box RNA Helicases
  • Dendritic Cells
  • RNA, Double-Stranded

Identity

PubMed Central ID

  • PMC3652560

Scopus Document Identifier

  • 79959344720

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2011.03.027

PubMed ID

  • 21703541

Additional Document Info

volume

  • 34

issue

  • 6