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K1 and K15 of Kaposi sarcoma-associated herpes virus are functional homologues of latent membrane protein 2A of Epstein-Barr virus

ABSTRACT: LMP2A of Epstein-Barr virus is a receptor that mimics an activated B cell receptor, BCR. K1 and K15, related receptors of Kaposi sarcoma-associated herpes virus, KSHV, are expressed in virus-associated tumors but their functions are less obvious. We addressed this uncertainty with mutant EBVs encoding the KSHV genes K1 or K15 in lieu of LMP2A and infected primary human B cells with them. K1 and K15 encoded proteins appear to have noncomplementing redundant functions in this model but our findings suggest that both KSHV proteins can replace LMP2A’s key activities contributing to the survival, activation and proliferation of B cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE53914 | GEO | 2014/04/01

SECONDARY ACCESSION(S): PRJNA233952

REPOSITORIES: GEO

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K1 and K15 of Kaposi sarcoma-associated herpes virus are functional homologues of latent membrane protein 2A of Epstein-Barr virus

Project description:LMP2A of Epstein-Barr virus is a receptor that mimics an activated B cell receptor, BCR. K1 and K15, related receptors of Kaposi sarcoma-associated herpes virus, KSHV, are expressed in virus-associated tumors but their functions are less obvious. We addressed this uncertainty with mutant EBVs encoding the KSHV genes K1 or K15 in lieu of LMP2A and infected primary human B cells with them. K1 and K15 encoded proteins appear to have noncomplementing redundant functions in this model but our findings suggest that both KSHV proteins can replace LMP2AM-bM-^@M-^Ys key activities contributing to the survival, activation and proliferation of B cells. We infected unsorted B cells with the four virus stocks, wt EBV, K1 EBV, K15 EBV or M-NM-^TLMP2A EBV, adjusted to yield similar rates of EBV-activated and growth transformed B cells. Eight days p.i. activated B cells in the lymphocyte gate were collected by FACS sorting and their RNAs analyzed with the aid of the Affymetrix GeneChip Human Gene 1.0 ST Array covering the whole transcriptome of approx. 29,000 annotated human genes. B cell preparations from four different donors were infected and analyzed accordingly.

2014-04-01 | E-GEOD-53914 | biostudies-arrayexpress

Immunization of mice with virus-like vesicles of Kaposi sarcoma-associated herpesvirus reveals a role of ORF4 in complement-mediated neutralization

Project description:The development of a prophylactic vaccine for Kaposi sarcoma-associated Herpesvirus (KSHV) would prevent consequences from infection including disorders such as Kaposi sarcoma and primary effusion lymphoma. Here, we study the immunogenicity of noninfectious virus-like vesicles (VLVs) of KSHV as a potential future vaccine platform. VLVs present a repertoire of viral structural proteins but are noninfectious due to a defect in capsid formation that prevents viral DNA packaging. Immunization of mice with adjuvanted VLVs results in virus-specific antibodies and T cells. These antibodies neutralize viral infection, and this neutralization is enhanced by the complement system. Complement-enhanced neutralization is dependent on antibodies targeting the SCR region of viral ORF4. However, this activity was not present in serum from KSHV-infected humans. Our study highlights an important role of antibody effector functions in the development of a future KSHV vaccine

2023-02-01 | PXD035478 | Pride

Widespread traces of lytic KSHV in primary effusion lymphoma at single-cell resolution

Project description:Cancer cells of primary effusion lymphoma (PEL) often contain both Kaposi sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV). We measured the interplay of human, KSHV, and EBV transcription in a cell culture model of PEL using single-cell RNA sequencing. The data detect widespread trace expression of lytic KSHV genes.

2020-10-13 | GSE154900 | GEO

Lymphatic endothelial cells (LEC) transfected with the KSHV microRNA cluster

Project description:Kaposi sarcoma is the most common cancer in AIDS patients and is typified by red skin lesions. The disease is caused by the KSHV virus (HHV8) and is recognisable by its distinctive red skin lesions. The lesions are KSHV-infected spindle cells, most commonly the lymphatic endothelial and blood vessel endothelial cells (LEC and BEC), plus surrounding stroma. The KSHV virus expresses multiple microRNA in a single cluster. Here we test the effects of this KSHV microRNA cluster in LEC cells using Affymetrix hgu133plus2 chips.

2009-09-30 | GSE16355 | GEO

Transcription profiling of human lymphatic edothelial cells transfected with the KSHV microRNA cluster

2009-10-10 | E-GEOD-16355 | biostudies-arrayexpress

BJAB Cell Lines Transduced with lentiviral vector pNL-SIN-CMV-AcGFP expressing KSHV miRNAs miR-K1, miR-K12-11, or miR-K4-3p

Project description:BJAB cells were infected with pNL-SIN-CMV-AcGFP (see accession number GSE8867 for data) or pNL-SIN-CMV-AcGFP expressing KSHV miR-K1, miR-K12-11 or miR-K4-3p and sorted 48 hours after infection. 12 or 16 days after transduction, cytoplasmic RNA was harvested and gene expression analysis of independent BJAB cell pools was performed using Human Operon v3.0.2 arrays. Each sample was run against Universal Human Reference RNA, Stratagene. The samples listed here were processed in parallel to those with accession number GSE8867, which includes all matched control cell lines. 6 independent B cell pools each expressing KSHV miR-K1, miRK12-11, or miR-K4-3p are included. Matched controls include unmodified BJAB (3 arrays) and cells transducted with parental vector pNL-SIN-CMV-AcGFP (6 replicates).

2011-11-16 | E-GEOD-31746 | biostudies-arrayexpress

Lymphatic endothelial cells (LEC) treated with a MAF-targeted siRNA

Project description:Kaposi sarcoma is the most common cancer in AIDS patients and is typified by red skin lesions. The disease is caused by the KSHV virus (HHV8) and is recognisable by its distinctive red skin lesions. The lesions are KSHV-infected spindle cells, most commonly the lymphatic endothelial and blood vessel endothelial cells (LEC and BEC), plus surrounding stroma. The KSHV virus expresses multiple MAF-downregulating microRNA. Here we test the effects of MAF silencing by siRNA in LEC cells using Affymetrix hgu133plus2 chips.

2009-09-30 | GSE16356 | GEO

Next Generation Sequencing of transfected NC K1 cells and transfected si-NEAT1_2 K1 cells

Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of transfected NC K1 cells and transfected si-NEAT1_2 K1 cells. The goals of this study are to analysis the different mRNA expression between transfected NC K1 cells and transfected si-NEAT1_2 K1 cells. Quantitative reverse transcription polymerase chain reaction (qRT–PCR) methods and to evaluate protocols for optimal high-throughput data analysis. We performed mRNA-seq in the NEAT1_2 knockdown group and NC group in the K1 cell line. We found that after knockdown of NEAT1_2, 615 mRNAs were upregulated and 2364 mRNAs were downregulated.

2020-12-05 | GSE159905 | GEO

RNAi knock down of MAFin human lymphatic endothelial cells

Project description:Kaposi sarcoma is the most common cancer in AIDS patients and is typified by red skin lesions. The disease is caused by the KSHV virus (HHV8) and is recognisable by its distinctive red skin lesions. The lesions are KSHV-infected spindle cells, most commonly the lymphatic endothelial and blood vessel endothelial cells (LEC and BEC), plus surrounding stroma. The KSHV virus expresses multiple MAF-downregulating microRNA. Here we test the effects of MAF silencing by siRNA in LEC cells using Affymetrix hgu133plus2 chips. Experiment Overall Design: There are n=3 of 1. LEC control cells transfected with a non-targeting siRNA, 2. LEC transfected with a MAF-targeting siRNA

2009-10-10 | E-GEOD-16356 | biostudies-arrayexpress

Comparison of the transcriptome of K-LEC spheroids to control LEC spheroids

Project description:Kaposi sarcoma is the most common cancer in AIDS patients and is typified by red skin lesions.The disease is caused by the KSHV virus (HHV8) and is recognisable by its distinctive red skin lesions. The lesions are KSHV infected spindle cells expressing markers of the lymphatic endothelial and blood vessel endothelial cells as well as other cell types. The effects of KSHV infection of lymphatic endothelial cells (LEC) cultured in 3D matrix for three days were assayed using Affymetrix hgu133plus2 chips. There are n=3 of 1. control LEC spheroids (LEC), 2. KSHV infected LEC spheroids (K-LEC)

2011-12-21 | E-GEOD-22522 | biostudies-arrayexpress

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