Barrier-to-autointegration Factor 1 (BAF) Promotes Gammaherpesvirus Reactivation from Latency
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA826747 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18750785_1.fastq.gz | Fastqsanger.gz | |||
| SRR18750785_2.fastq.gz | Fastqsanger.gz | |||
| SRR18750786_1.fastq.gz | Fastqsanger.gz | |||
| SRR18750786_2.fastq.gz | Fastqsanger.gz | |||
| SRR18750787_1.fastq.gz | Fastqsanger.gz |
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Project description:Gammaherpesviruses, including Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), are DNA viruses that are globally associated with human cancers and establish lifelong latency in the human population. Detection of gammaherpesviral infection by the cGAS-STING innate immune DNA-sensing pathway is critical for suppressing viral reactivation from latency, a process that promotes viral pathogenesis and transmission. We report that Barrier-to-autointegration factor 1 (BAF)-mediated suppression of the cGAS-STING signaling pathway is necessary for reactivation of KSHV and EBV. We demonstrate a novel role for BAF in destabilizing cGAS expression and show that BAF expression in latently infected, reactivating, or uninfected cells leads to suppression of type I interferon-mediated antiviral responses and inhibition of viral replication. Furthermore, BAF overexpression resulted in decreased cGAS expression at the protein level. These results establish BAF as a key regulator of the lifecycle of gammaherpesviruses and a potential target for treating viral infections and malignancies.
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Project description:Gammaherpesviruses, including Kaposi sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), are DNA viruses that are globally associated with human cancers and establish lifelong latency in the human population. Detection of gammaherpesviral infection by the cGAS-STING innate immune DNA-sensing pathway is critical for suppressing viral reactivation from latency, a process that promotes viral pathogenesis and transmission. We report that barrier-to-autointegration factor 1 (BAF)-mediated suppression of the cGAS-STING signaling pathway is necessary for reactivation of KSHV and EBV. We demonstrate a role for BAF in destabilizing cGAS expression and show that inhibiting BAF expression in latently infected, reactivating, or uninfected cells leads to increased type I interferon-mediated antiviral responses and decreased viral replication. Furthermore, BAF overexpression resulted in decreased cGAS expression at the protein level. These results establish BAF as a key regulator of the lifecycle of gammaherpesviruses and a potential target for treating viral infections and malignancies.
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Project description:We applied a custom tiled microarray to examine murine gammaherpesvirus 68 (MHV68) polyadenylated transcript expression in a timecourse of de novo infection of fibroblast cells and following phorbol ester-mediated reactivation from a latently-infected B cell line. During de novo infection, all ORFs were transcribed and clustered into four major temporal groups that were overlapping, yet distinct from clusters based on the phorbol ester-stimulated B cell reactivation timecourse. High-density transcript analysis at two-hour intervals during de novo infection mapped gene boundaries with a 20-nt resolution, including a previously undefined ORF73 transcript and the MHV68 ORF63 homolog of KSHV vNLRP1. ORF6 transcript initiation was mapped by tiled array and confirmed by 5' RACE. The ~1.3 kb region upstream of ORF6 was responsive to lytic infection and MHV68 RTA, identifying a novel RTA-responsive promoter. Transcription in intergenic regions consistent with the previously defined expressed genomic regions was detected during both types of productive infection. We conclude that the MHV68 transcriptome during de novo fibroblast infection and upon phorbol ester-stimulated B cell reactivation is dynamic and distinct, highlighting the need to evaluate further transcript structure and the context-dependent molecular events that govern viral gene expression during chronic infection. This SuperSeries is composed of the following subset Series: GSE35863: Tiled Array Experiment of Murine Gammaherpesvirus 68 Transcripts In Newly Infected Fibroblasts GSE35865: Tiled Array Experiment of Murine Gammaherpesvirus 68 Transcripts Upon TPA-Stimulated Reactivation From Latency Refer to individual Series
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