Sec13 is a positive regulator of VISA-mediated antiviral signaling
- 3 Downloads
Viral infection triggers the innate antiviral immune response that rapidly produces type I interferons in most cell types to combat viruses invading. Upon viral infection, the cytoplasmic RNA sensors RIG-I/MDA5 recognize viral RNA, and then RIG-I/MDA5 is transported to mitochondria interacting with VISA through the CARD domain. From there, VISA recruits downstream antiviral signaling pathways molecules, such as TRAFs and TBK1. Eventually, IRF3 is phosphorylated and type I IFNs are induced to fight as the first line of defense against viruses. However, it remains unclear how VISA acts as a scaffold to assemble the signalosome in RIG-I-mediated antiviral signaling. Here, we demonstrated Sec13 as a novel component that was involved in VISA-mediated antiviral signaling pathway. The co-immunoprecipitation assays showed that Sec13 specifically interacts with VISA. Overexpression of Sec13 increases VISA’s aggregation and ubiquitination and significantly enhances the phosphorylation and dimerization of IRF3, facilitating the IFN-β production. Conversely, the knockdown of Sec13 attenuates Sendai virus-induced and VISA-mediated IRF3 activation and the production of IFNβ, thus weakens antiviral immune activity.
KeywordsSec13 VISA/MAVS RLR antiviral signaling Interferon IRF3
We are grateful to Dr. Hong-Bing Shu (Medical Research Institute, Wuhan University) for his helping for providing plasmids and other reagents assistance. This work was supported by Grants from the National Natural Science Foundation of China (Grant Nos. 31370876, 31570876), the Natural Science Foundation of Jiangxi Province (20143ACB20004, 20161BAB204177), the Open Project Program of Key Laboratory of Functional Small Organic Molecule, Ministry of Education, and Jiangxi Normal University (KLFS-KF-201407), Postdoctoral Start Fund of Jiangxi Normal University (2014A).
LX designed the research. TC, TX, and DW performed the experiments. LX and TC did data analysis and discussion. TC and LX wrote the manuscript.
Compliance with ethical standards
Conflict of interest
The author declares no conflict of interest.
Human and animal participants
This article does not contain any studies with human participants or animals performed by any of the authors.
- 9.F. Ferrage, K. Dutta, E. Nistal-Villan, J.R. Patel, M.T. Sanchez-Aparicio, P. De Ioannes, A. Buku, G.G. Aseguinolaza, A. Garcia-Sastre, A.K. Aggarwal, Structure and dynamics of the second CARD of human RIG-I provide mechanistic insights into regulation of RIG-I activation. Structure 20, 2048–2061 (2012)CrossRefPubMedPubMedCentralGoogle Scholar
- 21.S. Paz, Q. Sun, P. Nakhaei, R. Romieu-Mourez, D. Goubau, I. Julkunen, R. Lin, J. Hiscott, Induction of IRF-3 and IRF-7 phosphorylation following activation of the RIG-I pathway. Cell. Mol. Biol. (Noisy-le-grand) 52, 17–28 (2006)Google Scholar
- 23.S. Paz, M. Vilasco, S.J. Werden, M. Arguello, D. Joseph-Pillai, T. Zhao, T.L. Nguyen, Q. Sun, E.F. Meurs, R. Lin, J. Hiscott, A functional C-terminal TRAF3-binding site in MAVS participates in positive and negative regulation of the IFN antiviral response. Cell Res. 21, 895–910 (2011)CrossRefPubMedPubMedCentralGoogle Scholar
- 26.D. Vitour, S. Dabo, M. Ahmadi Pour, M. Vilasco, P.O. Vidalain, Y. Jacob, M. Mezel-Lemoine, S. Paz, M. Arguello, R. Lin, F. Tangy, J. Hiscott, E.F. Meurs, Polo-like kinase 1 (PLK1) regulates interferon (IFN) induction by MAVS. J. Biol. Chem. 284, 21797–21809 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
- 35.C. Castanier, N. Zemirli, A. Portier, D. Garcin, N. Bidere, A. Vazquez, D. Arnoult, MAVS ubiquitination by the E3 ligase TRIM25 and degradation by the proteasome is involved in type I interferon production after activation of the antiviral RIG-I-like receptors. BMC Biol. 10, 44 (2012)CrossRefPubMedPubMedCentralGoogle Scholar
- 58.J. Zhu, T. Davoli, J.M. Perriera, C.R. Chin, G.D. Gaiha, S.P. John, F.D. Sigiollot, G. Gao, Q. Xu, H. Qu, T. Pertel, J.S. Sims, J.A. Smith, R.E. Baker, L. Maranda, A. Ng, S.J. Elledge, A.L. Brass, Comprehensive identification of host modulators of HIV-1 replication using multiple orthologous RNAi reagents. Cell Rep. 9, 752–766 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
- 59.T.G. Moreira, L. Zhang, L. Shaulov, A. Harel, S.K. Kuss, J. Williams, J. Shelton, B. Somatilaka, J. Seemann, J. Yang, R. Sakthivel, D.R. Nussenzveig, A.M. Faria, B.M. Fontoura, Sec13 regulates expression of specific immune factors involved in inflammation in vivo. Sci Rep. 5, 17655 (2015)CrossRefPubMedPubMedCentralGoogle Scholar