DHX15 senses double-stranded RNA in myeloid dendritic cells

J Immunol. 2014 Aug 1;193(3):1364-72. doi: 10.4049/jimmunol.1303322.

Hongbo Lu ¹, Ning Lu ¹, Leiyun Weng ¹, Bin Yuan ², Yong-Jun Liu ³, Zhiqiang Zhang ⁴

Affiliations

1 Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204; and.
2 Immunobiology and Transplant Research, Houston Methodist Hospital and Houston Methodist Research Institute, Houston, TX 77030.
3 Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204; and yong-jun.liu@baylorhealth.edu zzhang@houstonmethodist.org.
4 Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204; and Immunobiology and Transplant Research, Houston Methodist Hospital and Houston Methodist Research Institute, Houston, TX 77030 yong-jun.liu@baylorhealth.edu zzhang@houstonmethodist.org.

PMID: 24990078 DOI: 10.4049/jimmunol.1303322

Abstract

Many members of the DEXD/H box helicase family play important roles in the innate immune system against viral Infection. Therefore, we isolated dsRNA complex in myeloid dendritic cells. We found that DHx15, a DEXDc helicase family member, is one of the components of this complex. Knockdown of DHX15 expression by short hairpin RNA efficiently reduced the ability of myeloid dendritic cells to produce IFN-β, IL-6, and TNF-α in response to dsRNA and RNA virus. DHX15 specifically bound polyinosine-polycytidylic acid via its helicase C-terminal domain. DHX15 interacted with MAVS and formed a complex following stimulation with polyinosine-polycytidylic acid. The N-terminal domain containing a DEXDc motif in DHX15 bound the C terminus of MAVS. DHX15 is required to activate IRF3 phosphorylation as well as NF-κB and MAPK signaling during RNA virus Infection. We, therefore, identified DHX15 as a new RNA virus sensor mediated by MAVS to activate the immune responses to RNA.

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