Regulation of Tripartite Motif-Containing Proteins on Immune Response and Viral Evasion

Zhang, Xiuzhong; Li, Fuhuang; Wang, Xiaojia

doi:10.3389/fmicb.2021.794882

Cited by 6 publications

(2 citation statements)

References 131 publications

(204 reference statements)

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“…Given that earlier studies have demonstrated the antiviral activities of various TRIMs [ 84 ], we focused on TRIMs whose function primarily involved innate immune signaling pathways: TLRs, RIG-like receptors, and cyclic GMP-AMP synthase (cGAS)-stimulator of IFN genes (STING). Activation of these pathways leads to the production of IFNs and IL27 that promote the induction of ISG expression [ 25 , 85 ]. For instance, TRIM25 is essential for RIG-I-mediated antiviral activity [ 86 ].…”

Section: Discussionmentioning

confidence: 99%

Interleukin 27, Similar to Interferons, Modulates Gene Expression of Tripartite Motif (TRIM) Family Members and Interferes with Mayaro Virus Replication in Human Macrophages

Hernández-Sarmiento,

Tamayo-Molina,

Valdés-López

et al. 2024

Viruses

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Background: The Tripartite motif (TRIM) family includes more than 80 distinct human genes. Their function has been implicated in regulating important cellular processes, including intracellular signaling, transcription, autophagy, and innate immunity. During viral infections, macrophages are key components of innate immunity that produce interferons (IFNs) and IL27. We recently published that IL27 and IFNs induce transcriptional changes in various genes, including those involved in JAK-STAT signaling. Furthermore, IL27 and IFNs share proinflammatory and antiviral pathways in monocyte-derived macrophages (MDMs), resulting in both common and unique expression of inflammatory factors and IFN-stimulated genes (ISGs) encoding antiviral proteins. Interestingly, many TRIM proteins have been recognized as ISGs in recent years. Although it is already very well described that TRIM expression is induced by IFNs, it is not fully understood whether TRIM genes are induced in macrophages by IL27. Therefore, in this study, we examined the effect of stimulation with IL27 and type I, II, and III IFNs on the mRNA expression profiles of TRIM genes in MDMs. Methods: We used bulk RNA-seq to examine the TRIM expression profile of MDMs treated with IFNs or IL27. Initially, we characterized the expression patterns of different TRIM subfamilies using a heatmap. Subsequently, a volcano plot was employed to identify commonly differentially expressed TRIM genes. Additionally, we conducted gene ontology analysis with ClueGO to explore the biological processes of the regulated TRIMs, created a gene-gene interaction network using GeneMANIA, and examined protein-protein interactions with the STRING database. Finally, RNA-seq data was validated using RT-qPCR. Furthermore, the effect of IL27 on Mayaro virus replication was also evaluated. Results: We found that IL27, similar to IFNs, upregulates several TRIM genes’ expression in human macrophages. Specifically, we identified three common TRIM genes (TRIM19, 21, and 22) induced by IL27 and all types of human IFNs. Additionally, we performed the first report of transcriptional regulation of TRIM19, 21, 22, and 69 genes in response to IL27. The TRIMs involved a broad range of biological processes, including defense response to viruses, viral life cycle regulation, and negative regulation of viral processes. In addition, we observed a decrease in Mayaro virus replication in MDMs previously treated with IL27. Conclusions: Our results show that IL27, like IFNs, modulates the transcriptional expression of different TRIM-family members involved in the induction of innate immunity and an antiviral response. In addition, the functional analysis demonstrated that, like IFN, IL27 reduced Mayaro virus replication in MDMs. This implies that IL27 and IFNs share many similarities at a functional level. Moreover, identifying distinct TRIM groups and their differential expressions in response to IL27 provides new insights into the regulatory mechanisms underlying the antiviral response in human macrophages.

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Section: Discussionmentioning

confidence: 99%

Interleukin 27, Similar to Interferons, Modulates Gene Expression of Tripartite Motif (TRIM) Family Members and Interferes with Mayaro Virus Replication in Human Macrophages

Hernández-Sarmiento,

Tamayo-Molina,

Valdés-López

et al. 2024

Viruses

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“…Understanding the mechanisms by which TRIMs participate in viral immune evasion can help to identify new molecular targets for treating and preventing viral infectious diseases. It is crucial to study the dynamic interactions between TRIMs and viral proteins to develop strategies to combat viral infections [ 192 ]. Romagnoli et al found that TRIM32, a novel player involved in the intracellular response to Mycobacterium tuberculosis ( M. tb ) infection in macrophages, promotes autophagy-mediated M. tb degradation.…”

Section: Translating the Diverse Functions Of Trim Proteins Into Clin...mentioning

confidence: 99%

Multipronged regulation of autophagy and apoptosis: emerging role of TRIM proteins

Ahsan,

Shariq,

Surolia

et al. 2024

Cell Mol Biol Lett

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TRIM proteins are characterized by their conserved N-terminal RING, B-box, and coiled-coil domains. These proteins are efficient regulators of autophagy, apoptosis, and innate immune responses and confer immunity against viruses and bacteria. TRIMs function as receptors or scaffold proteins that target substrates for autophagy-mediated degradation. Most TRIMs interact with the BECN1-ULK1 complex to form TRIMosomes, thereby efficiently targeting substrates to autophagosomes. They regulate the functions of ATG proteins through physical interactions or ubiquitination. TRIMs affect the lipidation of MAP1LC3B1 to form MAP1LC3B2, which is a prerequisite for phagophore and autophagosome formation. In addition, they regulate MTOR kinase and TFEB, thereby regulating the expression of ATG genes. TRIM proteins are efficient regulators of apoptosis and are crucial for regulating cell proliferation and tumor formation. Many TRIM proteins regulate intrinsic and extrinsic apoptosis via the cell surface receptors TGFBR2, TNFRSF1A, and FAS. Mitochondria modulate the anti- and proapoptotic functions of BCL2, BAX, BAK1, and CYCS. These proteins use a multipronged approach to regulate the intrinsic and extrinsic apoptotic pathways, culminating in coordinated activation or inhibition of the initiator and executor CASPs. Furthermore, TRIMs can have a dual effect in determining cell fate and are therefore crucial for cellular homeostasis. In this review, we discuss mechanistic insights into the role of TRIM proteins in regulating autophagy and apoptosis, which can be used to better understand cellular physiology. These findings can be used to develop therapeutic interventions to prevent or treat multiple genetic and infectious diseases. Graphical Abstract

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TRIM46 accelerates H1N1 influenza virus-induced ferroptosis and inflammatory response by regulating SLC7A11 ubiquitination

Zhou,

Bao,

Chen

2024

J Bioenerg Biomembr

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Regulation of Tripartite Motif-Containing Proteins on Immune Response and Viral Evasion

Cited by 6 publications

References 131 publications

Interleukin 27, Similar to Interferons, Modulates Gene Expression of Tripartite Motif (TRIM) Family Members and Interferes with Mayaro Virus Replication in Human Macrophages

Interleukin 27, Similar to Interferons, Modulates Gene Expression of Tripartite Motif (TRIM) Family Members and Interferes with Mayaro Virus Replication in Human Macrophages

Multipronged regulation of autophagy and apoptosis: emerging role of TRIM proteins

TRIM46 accelerates H1N1 influenza virus-induced ferroptosis and inflammatory response by regulating SLC7A11 ubiquitination

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