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Front. Immunol. | doi: 10.3389/fimmu.2018.00409

Negative Regulation of IFN-β Production by Alternative Splicing of Tumor necrosis factor receptor-associated factor 3 in Ducks

Xiaoqin Wei1, 2, Wei Qian1, Suolang Sizhu2,  Yongtao Li1,  Kelei Guo1,  Meilin Jin1 and  Hongbo Zhou1*
  • 1Huazhong Agricultural University, China
  • 2College of Agricultural and Animal Husbandry, Tibet University, China

Tumor necrosis factor receptor-associated factor 3 (TRAF3), an intracellular signal transducer, is identified as an important component of Toll-like receptors (TLRs) and RIG-I-like receptors (RLRs) induced type I interferon (IFN) signaling pathways. Previous studies have clarified TRAF3 function in mammals, but little is known about the role of TRAF3 in ducks. Here, we cloned and characterized the full-length duck TRAF3 (duTRAF3) gene and an alternatively spliced isoform of duTRAF3 (duTRAF3-S) lacking the fragment encoding amino acids 217 to 319, from duck embryo fibroblasts (DEFs). We found that duTRAF3 and duTRAF3-S played different roles in regulating IFN-β production in DEFs. duTRAF3 through its TRAF domain interacted with duMAVS or duTRIF, leading to the production of IFN-β. However, duTRAF3-S, containing the TRAF domain, was unable to bind duMAVS or duTRIF due to the intramolecular binding between the N- and C-terminal of duTRAF3-S that blocked the function of its TRAF domain. Further analysis identified that duTRAF3-S competed with duTRAF3 itself for binding to duTRAF3, perturbing duTRAF3 self-association, that impaired the assembly of duTRAF3-duMAVS/duTRIF complex, ultimately resulted in a reduced production of IFN-β. These findings suggest that duTRAF3 is an important regulator of duck innate immune signaling and reveal a novel mechanism for the negative regulation of IFN-β production via changing the formation of the homo-oligomerization of wild molecules, implying a novel regulatory role of truncated proteins.

Keywords: Duck, duTRAF3, duTRAF3-S, IFN-β, Negative regulation, Avian virus

Received: 08 Sep 2017; Accepted: 14 Feb 2018.

Edited by:

Uday Kishore, Brunel University, United Kingdom

Reviewed by:

Junji Xing, Houston Methodist Research Institute, United States
Shuobing Chen, Columbia University Medical Center, United States  

Copyright: © 2018 Wei, Qian, Sizhu, Li, Guo, Jin and Zhou. 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 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. Hongbo Zhou, Huazhong Agricultural University, Wuhan, China, hbzhou@mail.hzau.edu.cn