ILF3 contributes to the establishment of the antiviral type I interferon program

Watson, Samir F.; Bellora, Nicolás; Macías, Sara

doi:10.1101/809608

Cited by 5 publications

(7 citation statements)

References 61 publications

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“…In splicing factor analysis, ILF3 and SRSF7 are identified as a splicing factor affecting the splicing of exons. ILF3 plays a role in antiviral response by inducing the expression of interferon-stimulated genes [46]. In another computational analysis, SRSF7 is also predicted to have binding potential with SARS-CoV-2 RNA [47].…”

Section: Discussionmentioning

confidence: 99%

Systematic analysis of alternative splicing in time course data using Spycone

Lio

Louadi

Fenn

et al. 2022

Preprint

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During disease progression or organism development, alternative splicing (AS) may lead to isoform switches (IS) that demonstrate similar temporal patterns and reflect the AS co-regulation of such genes. Tools for dynamic process analysis usually neglect AS. Here we propose Spycone (https://github.com/yollct/spycone), a splicing-aware framework for time course data analysis. Spycone exploits a novel IS detection algorithm and offers downstream analysis such as network and gene set enrichment. We demonstrate the performance of Spycone using simulated and real-world data of SARS-CoV-2 infection.

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Section: Discussionmentioning

confidence: 99%

Systematic analysis of alternative splicing in time course data using Spycone

Lio

Louadi

Fenn

et al. 2022

Preprint

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“…In one case, A549 cells infected with Sendai virus exhibited decreased IFN upon small interfering RNA knockdown of ILF3 (28). A more recent study in HeLa cells found that NF110 enhanced translation of IFNB1 mRNA and a subset of ISGs (27). Given that the mechanisms regulating innate immune sensing and IFN production are known to be different between cell lines of immune and nonimmune origin (84), it is not particularly surprising that ILF3's function is context dependent.…”

Section: Discussionmentioning

confidence: 99%

“…We were particularly intrigued by the transcription factor ILF3, as it has been reported to negatively regulate IFN production during influenza infection in primary human bronchial epithelial cells (26). Additionally, under different experimental conditions in HeLa and A549 cells, ILF3 has been shown to promote the IFN response upon dsRNA stimulation (27,28). The gene encoding ILF3 produces two major isoforms, NF90 and NF110 (collectively named ILF3 for the purposes of this study), and both are known to act as transcriptional regulators (1113, 2931).…”

Section: Temporal Promoter and Transcriptome Analysis Predict Ilf3 As...mentioning

confidence: 99%

ILF3 Is a Negative Transcriptional Regulator of Innate Immune Responses and Myeloid Dendritic Cell Maturation

Nazitto

Amon

Mast

et al. 2021

The Journal of Immunology

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APCs such as myeloid dendritic cells (DCs) are key sentinels of the innate immune system. In response to pathogen recognition and innate immune stimulation, DCs transition from an immature to a mature state that is characterized by widespread changes in host gene expression, which include the upregulation of cytokines, chemokines, and costimulatory factors to protect against infection. Several transcription factors are known to drive these gene expression changes, but the mechanisms that negatively regulate DC maturation are less well understood. In this study, we identify the transcription factor IL enhancer binding factor 3 (ILF3) as a negative regulator of innate immune responses and DC maturation. Depletion of ILF3 in primary human monocyte-derived DCs led to increased expression of maturation markers and potentiated innate responses during stimulation with viral mimetics or classic innate agonists. Conversely, overexpression of short or long ILF3 isoforms (NF90 and NF110) suppressed DC maturation and innate immune responses. Through mutagenesis experiments, we found that a nuclear localization sequence in ILF3, and not its dual dsRNA-binding domains, was required for this function. Mutation of the domain associated with zinc finger motif of ILF3’s NF110 isoform blocked its ability to suppress DC maturation. Moreover, RNA-sequencing analysis indicated that ILF3 regulates genes associated with cholesterol homeostasis in addition to genes associated with DC maturation. Together, our data establish ILF3 as a transcriptional regulator that restrains DC maturation and limits innate immune responses through a mechanism that may intersect with lipid metabolism.

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“…A dsRNA binding protein ILF3 was identified from (8 total:4 unique) peptides in the infected sample. This protein was shown to be important for the establishment of dsRNA-induced anti-viral signaling and to either promote or inhibit the replication of diverse viruses (97)(98)(99)(100)(101). The ILF3 gene is expressed as multiple isoforms of the two major variants of 90KDa and 110KDa proteins.…”

Section: Identification Of Novel Factors Affecting Viral Replication ...mentioning

confidence: 99%

A Proximity Biotinylation Assay with a Host Protein Bait Reveals Multiple Factors Modulating Enterovirus Replication

Moghimi

Viktorova

Gabaglio

et al. 2022

Preprint

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As ultimate parasites, viruses depend on host factors for every step of their life cycle. On the other hand, cells evolved multiple mechanisms of detecting and interfering with viral replication. Yet, our understanding of the complex ensembles of pro- and anti-viral factors is very limited in virtually every virus-cell system. Here we investigated the proteins recruited to the replication organelles of poliovirus, a representative of the genus Enterovirus of the Picornaviridae family. We took advantage of a strict dependence of enterovirus replication on a host protein GBF1, and established a stable cell line expressing a truncated GBF1 fused to APEX2 peroxidase that effectively supported viral replication upon inhibition of the endogenous GBF1. This construct biotinylated multiple host and viral proteins on the replication organelles. Among the viral proteins, the polyprotein cleavage intermediates were overrepresented, arguing that the GBF1 environment is linked to the viral polyprotein processing. The proteomics characterization of biotinylated host proteins identified those previously associated with the enterovirus replication, as well as more than 200 new factors recruited to the replication organelles. RNA metabolism proteins many of which normally localize in the nucleus constituted the largest group, underscoring the massive release of nuclear factors in the cytoplasm of infected cells and their involvement in the viral replication. Analysis of several newly identified proteins revealed both pro- and anti-viral factors, including a novel component of infection-induced stress granules. Depletion of these proteins similarly affected the replication of diverse enteroviruses indicating broad conservation of the replication mechanisms. Thus, our data significantly increase the knowledge about the organization of enterovirus replication organelles and may provide new targets for anti-viral interventions.

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ILF3 contributes to the establishment of the antiviral type I interferon program

Cited by 5 publications

References 61 publications

Systematic analysis of alternative splicing in time course data using Spycone

Systematic analysis of alternative splicing in time course data using Spycone

ILF3 Is a Negative Transcriptional Regulator of Innate Immune Responses and Myeloid Dendritic Cell Maturation

A Proximity Biotinylation Assay with a Host Protein Bait Reveals Multiple Factors Modulating Enterovirus Replication

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