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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02069

A cytosolic sensor, PmDDX41, binds double stranded-DNA and triggers the activation of an innate antiviral response in the shrimp Penaeus monodon via the STING-dependent signaling pathway

  • 1Center of Excellence for Molecular Biology and Genomics of Shrimp, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Thailand
  • 2National Science and Technology Development Agency (NSTDA), National Center for Genetic Engineering and Biotechnology (BIOTEC), Thailand
  • 3Laboratory of Molecular Immunobiology, Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma, Japan

Helicase DDX41 is a cytosolic sensor capable of detecting double-stranded DNA in mammals. However, the function of DDX41 remains poorly understood in invertebrates. In a previous study, we identified the first DDX41 sensor in the black tiger shrimp Penaeus monodon (PmDDX41) and showed that it played a role in anti-viral response. In the present study, we demonstrated that PmDDX41 was localized in the cytoplasm of shrimp hemocytes. However, PmDDX41 was localized in both the cytoplasm and nucleus of hemocytes in the presence of white spot syndrome virus (WSSV) infection or when stimulated by the nucleic acid mimics, poly(dA:dT) and poly(I:C). Similar results were observed when PmDDX41 was transfected into human embryonic kidney 293T (HEK293T) cells. Immunoprecipitation further demonstrated that PmDDX41 bound to biotin-labeled poly(dA:dT) but not poly(I:C). The overexpression of shrimp PmDDX41 and mouse stimulator of interferon gene (MmSTING) in HEK293T cells synergistically promoted IFN-β and NF-κB promotor activity via the DEADc domain. Co-immunoprecipitation (Co-IP) also confirmed that there was an interaction between PmDDX41 and STING after stimulation with poly(dA:dT) but not poly(I:C). Our study is the first to demonstrate that PmDDX41 acts as a cytosolic DNA sensor that interacts with STING via its DEADc domain to trigger the IFN-β and NF-κB signaling pathways, thus activating antiviral innate immune responses.

Keywords: Antiviral immune response, DDX41, Immune signaling pathway, PENAEUS MONODON, STING

Received: 18 Jun 2019; Accepted: 15 Aug 2019.

Copyright: © 2019 Soponpong, Amparyup, Kawai and Tassanakajon. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Anchalee -. Tassanakajon, Center of Excellence for Molecular Biology and Genomics of Shrimp, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Patumwan, 10330, Bangkok, Thailand, Anchalee.K@chula.ac.th