1. Academic Validation
  2. The RNA helicase DHX35 functions as a co-sensor for RIG-I-mediated innate immunity

The RNA helicase DHX35 functions as a co-sensor for RIG-I-mediated innate immunity

  • PLoS Pathog. 2024 Jul 22;20(7):e1012379. doi: 10.1371/journal.ppat.1012379.
Yuan Qiao 1 2 Shan Zhu 1 2 Ning Yang 2 Shan-Shan Zou 2 Bao Gao 2 Jing Wu 2 Chunyan Liu 2 Xiaoping Li 2 Yong-Jun Liu 2 Jingtao Chen 1 2
Affiliations

Affiliations

  • 1 Cancer Center, The First Hospital of Jilin University, Changchun, China.
  • 2 Laboratory for Tumor Immunology, The First Hospital of Jilin University, Changchun, China.
Abstract

RNA helicases are involved in the innate immune response against pathogens, including bacteria and viruses; however, their mechanism in the human airway epithelial cells is still not fully understood. Here, we demonstrated that DEAH (Asp-Glu-Ala-His) box polypeptide 35 (DHX35), a member of the DExD/H (Asp-Glu-x-Asp/His)-box helicase family, boosts Antiviral innate immunity in human airway epithelial cells. DHX35 knockdown attenuated the production of interferon-β (IFN-β), IL6, and CXCL10, whereas DHX35 overexpression increased their production. Upon stimulation, DHX35 was constitutively expressed, but it translocated from the nucleus into the cytosol, where it recognized cytosolic poly(I:C) and poly(dA:dT) via its HELICc domain. Mitochondrial Antiviral signaling protein (MAVS) acted as an adaptor for DHX35 and interacted with the HELICc domain of DHX35 using Amino acids 360-510. Interestingly, DHX35 interacted with retinoic acid-inducible gene 1 (RIG-I), enhanced the binding affinity of RIG-I with poly(I:C) and poly(dA:dT), and formed a signalsome with MAVS to activate interferon regulatory factor 3 (IRF3), NF-κB-p65, and MAPK signaling pathways. These results indicate that DHX35 not only acted as a cytosolic nucleic acid sensor but also synergized with RIG-I to enhance Antiviral immunity in human airway epithelial cells. Our results demonstrate a novel molecular mechanism for DHX35 in RIG-I-mediated innate immunity and provide a novel candidate for drug and vaccine design to control viral infections in the human airway.

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