SRA Suppresses Antiviral Innate Immune Response in Macrophages by Limiting TBK1 K63 Ubiquitination via Deubiquitinase USP15

Li, Lei; Luo, Jialiang; Zhu, Zhengyumeng; Xu, Qishan; Wang, Ping; Chang, Bo Yoon; Wang, Di; Yu, Lu; Xiao, Lü; Zhou, Jia; Zuo, Daming; Chen, Qing‐Yun

doi:10.1128/spectrum.02028-22

Cited by 5 publications

(4 citation statements)

References 37 publications

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“…Interferon upregulates nuclear deaminases such as APOBEC3A and APOBEC3B to exert a direct anti-HBV effect [ 81 , 82 ]. Macrophages, as essential cells for endogenous interferon production, can detect viruses through pattern recognition receptors (PRR) such as RIG-I and TBK1, mediate phosphorylation of interferon regulatory factor (IRF)-3 and IRF-7, and promote type I IFN gene transcription [ 83 , 84 ]. Thus, exosomes carrying miR-27b-3p secreted by infected hepatocytes inhibit endogenous IFN-α production in macrophages, possibly explaining the persistence of HBV.…”

Section: Hbv Modifies Exosomes To Reshape the Host Immune Microenviro...mentioning

confidence: 99%

Exosomes target HBV-host interactions to remodel the hepatic immune microenvironment

Wu,

Niu,

Shi

2024

J Nanobiotechnol

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Chronic hepatitis B poses a significant global burden, modulating immune cells, leading to chronic inflammation and long-term damage. Due to its hepatotropism, the hepatitis B virus (HBV) cannot infect other cells. The mechanisms underlying the intercellular communication among different liver cells in HBV-infected individuals and the immune microenvironment imbalance remain elusive. Exosomes, as important intercellular communication and cargo transportation tools between HBV-infected hepatocytes and immune cells, have been shown to assist in HBV cargo transportation and regulate the immune microenvironment. However, the role of exosomes in hepatitis B has only gradually received attention in recent years. Minimal literature has systematically elaborated on the role of exosomes in reshaping the immune microenvironment of the liver. This review unfolds sequentially based on the biological processes of exosomes: exosomes’ biogenesis, release, transport, uptake by recipient cells, and their impact on recipient cells. We delineate how HBV influences the biogenesis of exosomes, utilizing exosomal covert transmission, and reshapes the hepatic immune microenvironment. And based on the characteristics and functions of exosomes, potential applications of exosomes in hepatitis B are summarized and predicted. Graphical Abstract

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Section: Hbv Modifies Exosomes To Reshape the Host Immune Microenviro...mentioning

confidence: 99%

Exosomes target HBV-host interactions to remodel the hepatic immune microenvironment

Wu,

Niu,

Shi

2024

J Nanobiotechnol

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“… 872 The removal of K63 ubiquitination of TBK1 by USP15 negatively regulates TBK1 activity to suppress macrophage antiviral innate immune responses. 873 Pellino 1 (Peli1) can mediate TLR‐stimulated K63 ubiquitination of c‐IAP2 in microglia to trigger the Ub ligase activity of c‐IAP2, which catalyzes the K48 ubiquitination and degradation of TRAF3 and consequently induces proinflammatory cytokine production and the recruitment of autoimmune T cells in peripheral lymphoid organs to the CNS. 874 Peli1 also negatively regulates T‐cell activation and inhibits the development of autoimmunity through K48 ubiquitination‐dependent degradation of c‐Rel.…”

Section: Ubiquitinationmentioning

confidence: 99%

“…For example, the E3 Ub ligase NEURL3 promotes host antiviral immune response by catalyzing K63‐linked polyubiquitination of IRF7 at K375 872 . The removal of K63 ubiquitination of TBK1 by USP15 negatively regulates TBK1 activity to suppress macrophage antiviral innate immune responses 873 . Pellino 1 (Peli1) can mediate TLR‐stimulated K63 ubiquitination of c‐IAP2 in microglia to trigger the Ub ligase activity of c‐IAP2, which catalyzes the K48 ubiquitination and degradation of TRAF3 and consequently induces proinflammatory cytokine production and the recruitment of autoimmune T cells in peripheral lymphoid organs to the CNS 874 .…”

Section: Ubiquitinationmentioning

confidence: 99%

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Zhong

Xiao

Xie

et al. 2023

MedComm

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Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on the backbones or amino acid side chains of proteins and expand the diversity of proteins, which provides the basis for the emergence of organismal complexity. To date, more than 650 types of protein modifications, such as the most well‐known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short‐chain and long‐chain acylation modifications, redox modifications, and irreversible modifications, have been described, and the inventory is still increasing. By changing the protein conformation, localization, activity, stability, charges, and interactions with other biomolecules, PTMs ultimately alter the phenotypes and biological processes of cells. The homeostasis of protein modifications is important to human health. Abnormal PTMs may cause changes in protein properties and loss of protein functions, which are closely related to the occurrence and development of various diseases. In this review, we systematically introduce the characteristics, regulatory mechanisms, and functions of various PTMs in health and diseases. In addition, the therapeutic prospects in various diseases by targeting PTMs and associated regulatory enzymes are also summarized. This work will deepen the understanding of protein modifications in health and diseases and promote the discovery of diagnostic and prognostic markers and drug targets for diseases.

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“…E3 ubiquitin ligase RNF128 promotes DNA- and RNA virus-induced K63-linked polyubiquitination of TBK1 [ 9 ]. Scavenger receptor A, expressed mainly in macrophages, can deubiquitinate TBK1 by promoting the aggregation of USP15, a member of the cysteine protease deubiquitylases, thereby inhibiting DNA and RNA virus-induced IFN production [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

β-Glucan Induces Training Immunity to Promote Antiviral Activity by Activating TBK1

Wang,

Li,

Tian

et al. 2023

Viruses

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Many studies have shown that β-glucan induces a trained immune phenotype in innate immune cells to defend against bacterial and fungal infections. The specific mechanism involves cellular metabolism and epigenetic reprogramming. However, it is unclear whether β-glucan plays a role in antiviral infection. Therefore, this study investigated the role of trained immunity induced by Candida albicans and β-glucan in antiviral innate immunity. It showed that C. albicans and β-glucan promoted the expression of interferon-β (IFN-β) and interleukin-6 (IL-6) in mouse macrophages triggered by viral infection. In addition, β-glucan pretreatment attenuated the pathological damage induced by the virus in mouse lungs and promoted the expression of IFN-β. Mechanistically, β-glucan could promote the phosphorylation and ubiquitination of TANK Binding Kinase 1 (TBK1), a key protein of the innate immune pathway. These results suggest that β-glucan can promote innate antiviral immunity, and this bioactive material may be a potential therapeutic target for antiviral treatment.

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SRA Suppresses Antiviral Innate Immune Response in Macrophages by Limiting TBK1 K63 Ubiquitination via Deubiquitinase USP15

Cited by 5 publications

References 37 publications

Exosomes target HBV-host interactions to remodel the hepatic immune microenvironment

Exosomes target HBV-host interactions to remodel the hepatic immune microenvironment

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

β-Glucan Induces Training Immunity to Promote Antiviral Activity by Activating TBK1

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