HSPD1 interacts with IRF3 to facilitate interferon-beta induction.

Lan Lin,Pingan Wang,Jianqing Zhao,Lei Fu,Shan Pan,Meilin Jin,Cheng Liu,Anding Zhang,Xinlin Xu,Edward William Harhaj

doi:10.1371/journal.pone.0114874

Lan Lin, Pingan Wang + Show 8 more

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https://doi.org/10.1371/journal.pone.0114874

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Journal: PloS one	Publication Date: Dec 15, 2014
Citations: 17	License type: CC BY 4.0

Affiliation: Huazhong Agricultural University, Liaocheng University

Abstract

The production of IFN- I (IFN-α/β) is one of the earliest and most important host-protective responses. Interferon regulatory factor 3 (IRF3) is a critical transcriptional factor in the IFN-β signaling pathway. Although significant progress has been achieved in the regulation of IRF3, the process may be more complicated than previously considered. In the present study, heat shock protein 60 (HSP60, HSPD1) was identified as a novel IRF3-interacting protein. Overexpression of HSPD1 facilitated the phosphorylation and dimerization of IRF3 and enhanced IFN-β induction induced by SeV infection. In contrast, knockdown of endogenous HSPD1 significantly inhibited the signaling pathway. Furthermore, HSPD1 enhanced activation of the IFN-β promoter mediated by RIG-I, MDA-5, MAVS, TBK1 and IKKε but not IRF3/5D, a mock phosphorylated form of IRF3. The present study indicated that HSPD1 interacted with IRF3 and it contributed to the induction of IFN-β.

Highlights

The innate immune response is an important and evolutionarily conserved mechanism that protects the host against viral infection [1]
HSPD1 was identified as an interacting protein of activated Interferon regulatory factor 3 (IRF3)
FLAG-tagged IRF3 was exogenously expressed in the HEK293T cell line, and the cells were activated by overexpression of RIG-IN or mock transfected with the respective vector

Summary

Introduction

The innate immune response is an important and evolutionarily conserved mechanism that protects the host against viral infection [1]. The adaptor protein mitochondrial antiviral signaling protein (MAVS, known as IPS-1/VISA/Cardif) [7, 8] is activated and recruits non-canonical IKK family members, Tank-binding kinase 1 (TBK1) and inhibitor of kB kinase e (IKKe) [9, 10]. Both kinases can phosphorylate IRF-3, resulting in its activation, dimerization and translocation into the nucleus [11]. IRF3 together with other transcription factors assembles on the IFN-a/b promoter to initiate IFN-b transcription in a cooperative manner [12]

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