Abstract
Proteasome is a large protein complex, which degrades most intracellular proteins. It regulates numerous cellular processes, including the removal of misfolded or unfolded proteins, cell cycle control, and regulation of apoptosis. However, the function of proteasome subunits in viral immunity has not been well characterized. In this study, we identified PSMB1, a member of the proteasome β subunits (PSMB) family, as a negative regulator of innate immune responses during viral infection. Knockdown of PSMB1 enhanced the RNA virus-induced cytokine and chemokine production. Overexpression of PSMB1 abolished virus-induced activation of the interferon-stimulated response element (ISRE) and interferon beta (IFNβ) promoters. Mechanistically, PSMB1 inhibited the activation of RIG-I-like receptor (RLR) and Toll-like receptor 3 (TLR3) signaling pathways. PSMB1 was induced after viral infection and its interaction with IKK-ε promoted degradation of IKK-ε through the ubiquitin-proteasome system. Collectively, our study demonstrates PSMB1 is an important regulator of innate immune signaling.
Highlights
The innate immune system can rapidly detect invading viruses and establish an antiviral state [1].Following viral infection, viral nucleic acids can be recognized by pattern recognition receptors (PRRs) to initiate the cellular antiviral responses [2]
To explore the potential role of the proteasome β subunits (PSMB) family in cellular antiviral responses, we examined the expression pattern of the PSMB family in human THP-1 monocytes upon virus infection
To investigate whether PSMB1 is involved in the regulation of RIG-I-like receptor (RLR) signaling, we evaluated the effect of PSMB1 on RLR-dependent IFNβ activation
Summary
Viral nucleic acids can be recognized by pattern recognition receptors (PRRs) to initiate the cellular antiviral responses [2]. Toll-like receptors (TLRs) and RIG-I like receptors (RLRs) are the main PRRs that sense distinct types of RNA viruses [3,4]. PRRs trigger the activation of a downstream signaling pathway, leading to the production of type I IFNs and proinflammatory cytokines [5]. Secreted type I interferons (IFNs) further activate the Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) pathway, trigger the production of interferon stimulated genes (ISGs) and suppress viral replication and infection [6]. In addition to the antiviral activity, excessive production of type I IFNs is associated with inflammatory diseases and autoimmune diseases. Precise regulation of type I IFN production is a significant issue
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