Broadly Antiviral Activities of TAP1 through Activating the TBK1-IRF3-Mediated Type I Interferon Production

Abstract

Deeply understanding the virus-host interaction is a prerequisite for developing effective anti-viral strategies. Traditionally, the transporter associated with antigen processing type 1 (TAP1) is critical for antigen presentation to regulate adaptive immunity. However, its role in controlling viral infections through modulating innate immune signaling is not yet fully understood. In the present study, we reported that TAP1, as a product of interferon-stimulated genes (ISGs), had broadly antiviral activity against various viruses such as herpes simplex virus 1 (HSV-1), adenoviruses (AdV), vesicular stomatitis virus (VSV), dengue virus (DENV), Zika virus (ZIKV), and influenza virus (PR8) etc. This antiviral activity by TAP1 was further confirmed by series of loss-of-function and gain-of-function experiments. Our further investigation revealed that TAP1 significantly promoted the interferon (IFN)-β production through activating the TANK binding kinase-1 (TBK1) and the interferon regulatory factor 3 (IRF3) signaling transduction. Our work highlighted the broadly anti-viral function of TAP1 by modulating innate immunity, which is independent of its well-known function of antigen presentation. This study will provide insights into developing novel vaccination and immunotherapy strategies against emerging infectious diseases.

DNA methyltransferase inhibition induces dynamic gene expression changes in lung CD4+T cells of neonatal mice withE. colipneumonia

“…Tap1 encodes a membrane-bound antigen transporter responsible for transporting peptides across the endoplasmic reticulum for MHC-I molecule assembly (31, 32). Itself an interferon-stimulated gene, Tap1 can additionally stimulate the production of IFN-β (33). Oas1a encodes 2’-5’-oligoadenylate synthetase 1, an interferon-inducible protein that, upon binding to dsRNA, generates 2’-5’ oligoadenylates that activate RNaseL (34) , an antiviral endoribonuclease which is also essential for antibacterial immunity (35), (36).…”

Integrated analysis of immune parameters, miRNA-mRNA interaction, and immune genes expression in the liver of rainbow trout following infectious hematopoietic necrosis virus infection

“…TAP1, TAP2, and MHCI are responsible for presenting antigenic peptides from the cytosol to T cells (64). Furthermore, upregulation of TAP1 is conducive to the IFN-I production via activating the IRF3 signaling transduction (65). All of these molecules involved in antigen presentation have been proved to be related to the antiviral responses of host whether in fish or mammals (66,67).…”

Kynurenine-3-monooxygenase (KMO) broadly inhibits viral infections via triggering NMDAR/Ca2+ influx and CaMKII/ IRF3-mediated IFN-β production

“…The Western Blotting assay was performed as previously described [ 27 ]. Reagents and antibodies are listed in S4 Table .…”

“…To identify the potential genes with antiviral activity, we used a recombinant HSV-GFP-Luc reporter virus to screen the 288 ISGs induced by IFN-α and IFN-γ as we previously reported [23]. Besides the well-known antiviral genes including IRF1 [24], CH25H [25], IFITM2 [26], TAP1 [27], LY6E [28], we also identified some novel genes including KMO, SERPINA5, SLFN12, GPR146, and LIPG, which are uncharacterized with antiviral activity previously (Fig 1A). Our (A,B) 288 genes were screened by a luciferase-based analysis.…”