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FEAR antiviral response pathway is independent of interferons and countered by poxvirus proteins

ABSTRACT: FEAR antiviral response pathway is independent of interferons and countered by poxvirus proteins

PROVIDER: PRJNA770967 | ENA |

REPOSITORIES: ENA

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FEAR antiviral response pathway is independent of interferons and countered by poxvirus proteins

Project description:The human facilitates chromatin transcription (FACT) complex is a chromatin remodeller composed of human suppressor of Ty 16 homologue (hSpt16) and structure-specific recognition protein-1 subunits that regulates cellular gene expression. Whether FACT regulates host responses to infection remained unclear. We identify a FACT-mediated, interferon-independent, antiviral pathway that restricts poxvirus replication. Cell culture and bioinformatics approaches suggest that early viral gene expression triggers nuclear accumulation of SUMOylated hSpt16 subunits required for the expression of E26 transformation-specific sequence-1 (ETS-1)-a transcription factor that activates virus restriction programs. However, biochemical studies show that poxvirus-encoded A51R proteins block ETS-1 expression by outcompeting structure-specific recognition protein-1 binding to SUMOylated hSpt16 and by tethering SUMOylated hSpt16 to microtubules. Furthermore, A51R antagonism of FACT enhances poxvirus replication in human cells and virulence in mice. Finally, we show that FACT also restricts rhabdoviruses, flaviviruses and orthomyxoviruses, suggesting broad roles for FACT in antiviral immunity. Our study reveals the FACT-ETS-1 antiviral response (FEAR) pathway to be critical for eukaryotic antiviral immunity and describes a unique mechanism of viral immune evasion.

2023-12-31 | GSE185829 | GEO

MinION poxvirus seq

Project description:MinION poxvirus seq

| PRJEB8656 | ENA

Pyk2 suppresses contextual fear memory in an autophosphorylation-independent manner

Project description:We demonstrated that Pyk2 is a novel fear memory suppressor molecule and Pyk2 null mice provide a model for understanding fear-related disorders.

2022-02-02 | GSE180598 | GEO

Pyk2 suppresses contextual fear memory in an autophosphorylation-independent manner

Project description:We demonstrated that Pyk2 is a novel fear memory suppressor molecule and Pyk2 null mice provide a model for understanding fear-related disorders.

2022-02-02 | GSE158606 | GEO

Eutherian interferons

Project description:Eutherian interferons

| PRJEB36709 | ENA

Effect of type I interferons against HSV infection in cerebral organoids

Project description:Administration of recombinant interferons to 3D brain organoid cultures infected with HSV reveals a strong antiviral effect of IFN-alpha against HSV

2021-04-09 | GSE145496 | GEO

Antiviral function of type I and type III interferons in the olfactory epithelium

Project description:Antiviral function of type I and type III interferons in the olfactory epithelium

| PRJNA645461 | ENA

Wadden Sea poxvirus

Project description:Wadden Sea poxvirus Genome sequencing and assembly

| PRJNA896524 | ENA

Profiling whole-tissue metabolic reprogramming during cutaneous poxvirus infection and clearance

Project description:Background Vaccinia virus (VACV) infection induces prominent changes in host cell metabolism. Little is known about the global metabolic reprogramming that takes place in the whole tissue during viral infection. Here, we performed an unbiased longitudinal metabolomics study in VACV-infected mice to investigate metabolic changes in the tissue during infection. We assessed metabolites in homogenized skin over time in the presence or absence of antigen-specific T cells using untargeted mass spectrometry. VACV infection induced several significant metabolic changes, including in the levels of nucleic acid metabolites (reflecting the impact of viral replication on the skin metabolome). Furthermore, monocyte- and antiviral T cell-produced metabolites, including itaconic acid, glutamine, and glutathione, were significantly increased following infection, highlighting the immune response’s contribution to the global skin metabolome. Additional RNA-Seq of infected skin tissue recapitulated transcriptional changes identified via metabolomics. Overall, our study reveals the metabolic balance of viral replication and the antiviral immune response in the skin and identifies metabolic pathways that could contribute to cutaneous poxvirus control in vivo.

2023-11-09 | GSE236603 | GEO

Synaptic and transcriptomic features of fear matrix pyramidal neurons predict inefficient fear extinction

Project description:Trauma-related disorders arise from inefficient fear extinction and have immeasurable social and economic costs. Here, we characterized mouse phenotypes that spontaneously show individual differences in adaptive or maladaptive fear extinction and, before the traumatic experience, we found that specific morphological, electrophysiological and transcriptomic patterns of fear matrix pyramidal neurons predispose to trauma-related disorders. Finally, by using an optogenetic approach we showed the possibility to rescue the inefficient fear extinction activating fear matrix infralimbic pyramidal neurons

2023-06-02 | GSE209572 | GEO

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