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Interferon inhibits a model RNA virus via a limited set of inducible effector genes

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE233197 | GEO | 2023/05/26

REPOSITORIES: GEO

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Interferon inhibits a model RNA virus via a limited set of inducible effector genes.

Project description:Interferons control viral infection by inducing the expression of antiviral effector proteins encoded by interferon-stimulated genes (ISGs). The field has mostly focused on identifying individual antiviral ISG effectors and defining their mechanisms of action. However, fundamental gaps in knowledge about the interferon response remain. For example, it is not known how many ISGs are required to protect cells from a particular virus, though it is theorized that numerous ISGs act in concert to achieve viral inhibition. Here, we used CRISPR-based loss-of-function screens to identify a markedly limited set of ISGs that confer interferon-mediated suppression of a model alphavirus, Venezuelan equine encephalitis virus (VEEV). We show via combinatorial gene targeting that three antiviral effectors-ZAP, IFIT3, and IFIT1-together constitute the majority of interferon-mediated restriction of VEEV, while accounting for < 0.5% of the interferon-induced transcriptome. Together, our data suggest a refined model of the antiviral interferon response in which a small subset of "dominant" ISGs may confer the bulk of the inhibition of a given virus.

| S-EPMC10481653 | biostudies-literature

Interferon inhibits a model RNA virus via a limited set of inducible effector genes

Project description:Interferons control viral infection by inducing the expression of antiviral effector proteins encoded by interferon-stimulated genes (ISGs). The field has mostly focused on identifying individual antiviral ISG effectors and defining their mechanisms of action. However, fundamental gaps in knowledge about the interferon response remain. For example, it is not known how many ISGs are required to protect cells from a particular virus, though it is theorized that numerous ISGs act in concert to achieve viral inhibition. Here, we used CRISPR-based loss-of-function screens to identify a markedly limited set of ISGs that confer interferon-mediated suppression of a model alphavirus, Venezuelan equine encephalitis virus (VEEV). We show via combinatorial gene targeting that three antiviral effectors - ZAP, IFIT3, and IFIT1 - together constitute the majority of interferon-mediated restriction of VEEV, while accounting for less than 0.5% of the interferon-induced transcriptome. Together, our data suggests a refined model of the antiviral interferon response in which a small subset of "dominant" ISGs may confer the bulk of the inhibition of a given virus.

| S-SCDT-10_15252-EMBR_202356901 | biostudies-other

Interferon inhibits a model RNA virus via a limited set of inducible effector genes [ISG_CRISPR_Screen]

Project description:Host cells produce interferon (IFN) in response to viral infections. Secreted interferon results in the transcription and production of hundreds of interferon-stimulated genes (ISGs). An ISG-targeted CRISPR screen using IFN beta-treated U-2 OS cells was performed to determine which ISGs were required in order for host cells to suppress Venezuelan equine encephalitis virus (VEEV) infection.

2023-05-26 | GSE233196 | GEO

Interferon inhibits a model RNA virus via a limited set of inducible effector genes [GW_CRISPR_Screen]

Project description:Host cells produce interferon (IFN) in response to viral infections. Secreted interferon results in the transcription and production of hundreds of interferon-stimulated genes (ISGs). A genome-wide CRISPR screen using IFN beta-treated U-2 OS cells was performed to determine which ISGs were required in order for host cells to suppress Venezuelan equine encephalitis virus (VEEV) infection.

2023-05-26 | GSE233195 | GEO

Interferon inhibits a model RNA virus via a limited set of inducible effector genes [RNA-seq]

Project description:To investigate the transcripts induced by the cytokine interferon (IFN) β in U-2 OS cells, we treated U-2 OS cells with IFNβ 20U/mL for 6 and 24 hours and performed RNA-Seq to determine differentially expressed genes.

2023-05-26 | GSE233003 | GEO

Interferon inhibits a model RNA virus via a limited set of inducible effector genes

Project description:Interferon inhibits a model RNA virus via a limited set of inducible effector genes

| PRJNA975286 | ENA

Interferon inhibits a model RNA virus via a limited set of inducible effector genes [GW_CRISPR_Screen]

Project description:Interferon inhibits a model RNA virus via a limited set of inducible effector genes [GW_CRISPR_Screen]

| PRJNA975290 | ENA

Interferon inhibits a model RNA virus via a limited set of inducible effector genes [ISG_CRISPR_Screen]

Project description:Interferon inhibits a model RNA virus via a limited set of inducible effector genes [ISG_CRISPR_Screen]

| PRJNA975291 | ENA

Interferon inhibits a model RNA virus via a limited set of inducible effector genes [RNA-seq]

Project description:Interferon inhibits a model RNA virus via a limited set of inducible effector genes [RNA-seq]

| PRJNA974702 | ENA

Interferon-inducible cholesterol-25-hydroxylase inhibits hepatitis C virus replication via distinct mechanisms.

Project description:Cholesterol 25-hydroxylase (CH25H) as an interferon-stimulated gene (ISG) has recently been shown to exert broad antiviral activity through the production of 25-hydroxycholesterol (25HC), which is believed to inhibit the virus-cell membrane fusion during viral entry. However, little is known about the function of CH25H on HCV infection and replication and whether antiviral function of CH25H is exclusively mediated by 25HC. In the present study, we have found that although 25HC produced by CH25H can inhibit HCV replication, CH25H mutants lacking the hydroxylase activity still carry the antiviral activity against HCV but not other viruses such as MHV-68. Further studies have revealed that CH25H can interact with the NS5A protein of HCV and inhibit its dimer formation, which is essential for HCV replication. Thus, our work has uncovered a novel mechanism by which CH25H restricts HCV replication, suggesting that CH25H inhibits viral infection through both 25HC-dependent and independent events.

| S-EPMC4252895 | biostudies-other

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