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Single-cell RNA sequencing reveals a strong connection between Gadd45g upregulation and oncolytic HSV infection in tumor tissue

ABSTRACT: Single-cell RNA sequencing reveals a strong connection between Gadd45g upregulation and oncolytic HSV infection in tumor tissue

PROVIDER: PRJNA775970 | ENA |

REPOSITORIES: ENA

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Single-cell RNA sequencing reveals a strong connection between Gadd45g upregulation and oncolytic HSV infection in tumor tissue

Project description:The oncolytic effect of virotherapy derives from the intrinsic capability of the applied virus in selectively infecting and killing tumor cells. Although oncolytic viruses of various constructions have been shown to efficiently infect and kill tumor cells in vitro, the efficiency of these viruses to exert the same effect on tumor cells within tumor tissues in vivo has not been extensively investigated. Here we report our studies using single-cell RNA sequencing to comprehensively analyze the gene expression profile of tumor tissues following herpes simplex virus 2-based oncolytic virotherapy. Our data revealed the extent and cell types within the tumor microenvironment that could be infected by the virus. Moreover, we observed changes in the expression of cellular genes, including antiviral genes, in response to viral infection. One notable gene found to be upregulated significantly in oncolytic virus-infected tumor cells was Gadd45g, which is desirable for optimal virus replication. These results not only help reveal the precise infection status of the oncolytic virus in vivo, but also provide insight that may lead to the development of new strategies to further enhance the therapeutic efficacy of oncolytic virotherapy.

2021-10-31 | GSE186753 | GEO

Transcription profiling of human MPNST cancer cells infected with G207 an oncolytic HSV

Project description:We used microarrays to identify genes regulated during oncolytic HSV infection. Oncolytic herpes simplex viruses (oHSV) are promising anticancer therapeutics. We sought to identify alterations in gene expression during oHSV infection of human cancer cells. Human malignant peripheral nerve sheath tumor (MPNST) cells were infected with G207, an ICP34.5-deleted oHSV previously evaluated in clinical trials. G207-infected cells demonstrated massive degradation of cellular mRNAs, while a subset were upregulated. A gene signature of 21 oHSV-induced genes contained 7 genes known to be HSV-induced. Go ontology classification revealed that a majority of upregulated genes are involved in Jak/STAT signaling, transcriptional regulation, nucleic acid metabolism, protein synthesis and apoptosis. Ingenuity-defined functional networks highlighted nodes for AP-1 subunits and interferon signaling via STAT1, SOCS1, SOCS3 and RANTES. Upregulation of SOCS1 correlated with sensitivity of MPNST lines to G207 and depletion of SOCS1 reduced virus replication >1-log. The transcriptome of oHSV-induced genes may predict oncolytic efficacy and provides rationale for next generation oncolytics. Experiment Overall Design: 5 human MPNST cancer cell lines were infected with G207 or mock infected for 6 hours followed by RNA extraction and hybridization on Affymetrix microarrays.

2008-06-16 | E-GEOD-8717 | biostudies-arrayexpress

Expression data from Human MPNST cancer cells infected with G207 and oncolytic HSV

2007-08-08 | GSE8717 | GEO

Single-cell RNA sequencing reveals a strong connection between <i>Gadd45g</i> upregulation and oncolytic HSV infection in tumor tissue.

Project description: Not available

| S-EPMC8573104 | biostudies-literature

Comprehensive characterization of tumor immune landscape following oncolytic virotherapy by single-cell RNA sequencing

Project description:single-cell RNA sequencing analysis on carcinomas treated with an HSV-2-based oncolytic virus to characterize the immunogenic changes in the TME

2021-11-01 | GSE186548 | GEO

Identification of gene expression alteration in macrophage cells with oncolytic HSV

Project description:Identification of gene expression alteration in macrophage cells with oncolytic HSV

| PRJNA759634 | ENA

A Combination of Chemotherapy and Oncolytic Virotherapy Sensitizes Colorectal Adenocarcinoma to Immune Checkpoint Inhibitors in a cDC1-Dependent Manner

Project description:Comparison of transcriptome data in tumors from mice treated with combinations of mitomycin C, oncolytic HSV-1, anti-PD-1 and anti-CTLA-4.

2022-03-01 | GSE195924 | GEO

HSV-2 Triggers Upregulation of MALAT1 in CD4+ T cells and Promotes HIV Latency Reversal (scRNA-Seq)

Project description:HSV-2 coinfection is associated with increased HIV-1 viral loads and expanded tissue reservoirs, but the mechanisms are not well-defined. HSV-2 recurrences result in an influx of activated CD4+ T cells to sites of viral replication and an increase in activated CD4+ T cells in peripheral blood. We hypothesized that HSV-2 induces changes in these cells that facilitate HIV-1 reactivation and replication and tested this hypothesis in human CD4+ T cells and 2D10 cells, a model of HIV-1 latency. HSV-2 promoted latency reversal in HSV-2 infected and bystander 2D10 cells. Bulk and single-cell RNA sequencing studies of activated primary human CD4+ T cells identified decreased expression of HIV-1 restriction factors and increased expression of transcripts including MALAT1 that could drive HIV replication in both the HSV-2-infected and bystander cells. Transfection of 2D10 cells with VP16, an HSV-2 protein that regulates transcription, significantly upregulated MALAT1 expression, decreased trimethylation of lysine 27 on histone H3 protein, and triggered HIV latency reversal. Knockout of MALAT1 from 2D10 cells abrogated the response to VP16 and reduced the response to HSV-2 infection. These results demonstrate that HSV-2 contributes to HIV-1 reactivation through diverse mechanisms including upregulation of MALAT1 to release epigenetic silencing.

2023-05-07 | GSE229391 | GEO

HSV-2 Triggers Upregulation of MALAT1 in CD4+ T cells and Promotes HIV Latency Reversal (Bulk RNA-Seq)

2023-05-07 | GSE229390 | GEO

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

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