Effect of LANA deletion on the host gene expression during de novo KSHV infection of SLK cells.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Zsolt Toth
PROVIDER: E-GEOD-78282 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Human SLK cells were infected with wildtype (wt) and LANA knockout (KO) Kaposi's sarcoma-associated herpesvirus (KSHV), separately for 3 days. Cellular gene expression changes were identified upon the wild type and LANA KO KSHV virus infection compared to the uninfected SLK cells using the human gene expression microarray U133plus2.0.
2016-08-01 | GSE78282 | GEO
Project description:Gene expression profiling of three PEL cell lines compare to three Burkitt's lymphoma lines to figure out the changed genes under KSHV latent infection. Gene expression profiling of two time points on TIVE cells after infection by KSHV compare to TIVE cell without infection by KSHV to figure out the changed genes on TIVE cell under latent infection of KSHV. Gene expression profiling of four time points after inducing recombinant LANA protein expression when compare to no inducing BJAB/Tet-On/LANA cells to figure out the changed genes under the latency-associate nuclear antigen (LANA) of KSHV expression. Gene expression profiling of three time points after inducing recombinant LANA protein expression when compare to no inducing Jurkat/Tet-On/LANA cell line to figure out the changed genes under the latency-associate nuclear antigen (LANA) of KSHV expression. Gene expression profiling of two time points after inducing recombinant LANA protein expression when compare to no inducing 293/Tet-On/LANA cell line to figure out the changed genes under the latency-associate nuclear antigen (LANA) of KSHV expression. Keywords = TIVE Keywords = KSHV Keywords = LANA Keywords = PEL Keywords = BJAB Keywords = 293 Keywords = Jurkat Keywords: other
2004-10-27 | GSE1880 | GEO
Project description:Latency-associated nuclear antigen (LANA), a multifunctional protein expressed by the Kaposi sarcoma-associated herpesvirus (KSHV) in latently-infected cells, is required for stable maintenance of the viral episome. This is mediated by two interactions: LANA binds to specific sequences (LBS1 and 2) on viral DNA, and also engages host histones, tethering the viral genome to host chromosomes in mitosis. LANA has also been suggested to affect host gene expression, but both the mechanism(s) and role of this dysregulation in KSHV biology remain unclear. Here we have examined LANA interactions with host chromatin on a genome-wide scale using ChIP-seq, and show that LANA predominantly targets human genes near their transcriptional start sites (TSSs). These host LANA-binding sites are generally found within transcriptionally active promoters and display striking overrepresentation of a consensus DNA sequence virtually identical to the LBS1 motif in KSHV DNA. Comparison of the ChIP-seq profile with whole transcriptome (RNA-seq) data reveals that few of the genes that are differentially regulated in latent infection are occupied by LANA at their promoters. This suggests that direct LANA binding to promoters is not the prime determinant of altered host transcription in KSHV-infected cells. Most surprisingly, the association of LANA to both host and viral DNA is strongly disrupted during the lytic cycle of KSHV. This disruption can be prevented by the inhibition of viral DNA synthesis, suggesting the existence of novel and potent regulatory mechanisms linked to either viral DNA replication or late gene expression. Profiling of KSHV LANA positioning on the host genome and examination of gene expression from promoters bound by KSHV LANA.
2014-04-01 | E-GEOD-56144 | biostudies-arrayexpress
Project description:Gene expression profiling of three PEL cell lines compare to three Burkitt's lymphoma lines to figure out the changed genes under KSHV latent infection. Gene expression profiling of two time points on TIVE cells after infection by KSHV compare to TIVE cell without infection by KSHV to figure out the changed genes on TIVE cell under latent infection of KSHV. Gene expression profiling of four time points after inducing recombinant LANA protein expression when compare to no inducing BJAB/Tet-On/LANA cells to figure out the changed genes under the latency-associate nuclear antigen (LANA) of KSHV expression. Gene expression profiling of three time points after inducing recombinant LANA protein expression when compare to no inducing Jurkat/Tet-On/LANA cell line to figure out the changed genes under the latency-associate nuclear antigen (LANA) of KSHV expression. Gene expression profiling of two time points after inducing recombinant LANA protein expression when compare to no inducing 293/Tet-On/LANA cell line to figure out the changed genes under the latency-associate nuclear antigen (LANA) of KSHV expression.
2007-08-25 | E-GEOD-1880 | biostudies-arrayexpress
Project description:[original title] Mock or latently infected KSHV cells (BCBL, SLK and HFF) vs common reference (mixture of RNA from both infected and uninfected cells). Expression profiling of latently infected cells using a custom tiling microarray. SLK and HFF cells were infected and selected for rKSHV.219. Mock infected SLK and HFF cells served as controls for each of these two stably infected cells, respectively. BJAB cells served as uninfected controls for the BCBL-1 cells. Biological replicates were harvested and analyzed.
2010-03-24 | GSE20443 | GEO
Project description:Latency-associated nuclear antigen (LANA), a multifunctional protein expressed by the Kaposi sarcoma-associated herpesvirus (KSHV) in latently-infected cells, is required for stable maintenance of the viral episome. This is mediated by two interactions: LANA binds to specific sequences (LBS1 and 2) on viral DNA, and also engages host histones, tethering the viral genome to host chromosomes in mitosis. LANA has also been suggested to affect host gene expression, but both the mechanism(s) and role of this dysregulation in KSHV biology remain unclear. Here we have examined LANA interactions with host chromatin on a genome-wide scale using ChIP-seq, and show that LANA predominantly targets human genes near their transcriptional start sites (TSSs). These host LANA-binding sites are generally found within transcriptionally active promoters and display striking overrepresentation of a consensus DNA sequence virtually identical to the LBS1 motif in KSHV DNA. Comparison of the ChIP-seq profile with whole transcriptome (RNA-seq) data reveals that few of the genes that are differentially regulated in latent infection are occupied by LANA at their promoters. This suggests that direct LANA binding to promoters is not the prime determinant of altered host transcription in KSHV-infected cells. Most surprisingly, the association of LANA to both host and viral DNA is strongly disrupted during the lytic cycle of KSHV. This disruption can be prevented by the inhibition of viral DNA synthesis, suggesting the existence of novel and potent regulatory mechanisms linked to either viral DNA replication or late gene expression.
2014-04-01 | GSE56144 | GEO
Project description:[original title] Mock or latently infected KSHV cells (BCBL, SLK and HFF) vs common reference (mixture of RNA from both infected and uninfected cells). Expression profiling of latently infected cells using a custom tiling microarray. SLK and HFF cells were infected and selected for rKSHV.219. Mock infected SLK and HFF cells served as controls for each of these two stably infected cells, respectively. BJAB cells served as uninfected controls for the BCBL-1 cells. Biological replicates were harvested and analyzed. Two condition experiment: mock infected vs. latently infected cells. Three cell types.
2010-06-05 | E-GEOD-20443 | biostudies-arrayexpress
Project description:LANA is essential for tethering the KSHV genome to metaphase chromosomes and for modulating host-cell gene expression, but the binding sites in the host-chromosome remain unknown. Here, we use LANA-specific chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-Seq) to identify LANA binding sites in the viral and host-cell genomes of a latently infected pleural effusion lymphoma cell line BCBL1. LANA bound with high occupancy to the KSHV genome terminal repeats (TR), and to a few minor binding sites within the latency control region encoding that LANA transcript. We identified 256 LANA binding peaks with p < 0.01 and overlap in two independent ChIP-Seq experiments. We validated several of the high-occupancy binding sites by conventional ChIP assays and quantitative PCR. Two candidate DNA sequence motifs were identified, and confirmed to bind purified LANA protein, although with weaker affinity compared to viral TR binding site. More than half of the LANA binding sites (170/256) could be mapped to within 2.5 kb of a cellular gene transcript. Pathways and Gene Ontogeny (GO) analysis revealed that LANA binds to genes within the p53 and TNF regulatory network. Further analysis revealed partial overlap of LANA binding sites with STAT1 binding sites in several interferon (IFN)-g regulated genes. We show that ectopic expression of LANA can down-modulate IFN-g mediated activation of a subset of genes, including the TAP1 peptide transporter and proteasome subunit beta type 9 (PSMB9) required for class I antigen presentation. Our data provides a potential mechanism through which LANA may regulate several host cell pathways by direct binding to gene regulatory elements. Study of KSHV LANA
2012-01-06 | E-GEOD-34890 | biostudies-arrayexpress
Project description:Kaposi's sarcoma-associated herpesvirus (KSHV) establishes a latent infection, in which most viral genes are silenced except a few latent proteins such as latency-associated nuclear antigen (LANA). In latent viral chromatin, viral genes are poised to be transcribed, and KSHV LANA plays a major role in maintaining such transcription status. In the poised chromatins, LANA recruits cellular CHD4 (Chromodomain Helicase DNA binding protein 4) and suppresses inducible viral gene promoters. The CHD4 is known to regulate cell differentiation by restricting enhancer-promoter interactions and its mutation or overexpression deregulates the host cell transcription program and therefore associates with tumorigenesis. Here, we identified a putative CHD4 inhibitor from the LANA amino acid sequence from the LANA-CHD4 interaction surface. The small peptide interacts with CHD4 at its PHD domain with 14 nM KD (dissociation constant). The introduction of the peptide into the primary effusion lymphomas induces caspase-mediated CHD4 cleavage and subsequently triggered cell apoptosis and autophagy. A series of MTT assays demonstrated that the peptide preferentially killed lymphoma and leukemia cell lines at low micromolar concentrations, while peripheral mononuclear cells or adhesion cell lines were found to be more resistant to the peptide treatment. A monocyte cell differentiation model demonstrated that pre-treatment with the peptide at a low dose substantially enhanced transitioning into M2 macrophage (by reducing CHD4 occupancies from gene promoters), and globally altered the repertories of phorbol myristate acetate target genes in U937 cells. Finally, the PEL xenograft mouse model inhibited tumor growth without measurable side effects, and PEL cells isolated from xenograft tumors showed reduced CHD4 and LANA expression with terminally differentiated phenotype. We propose that the peptide isolated from the KSHV LANA sequence is biologically active and may function as a CHD4 inhibitor.
2024-03-01 | GSE228656 | GEO
Project description:Kaposi's sarcoma-associated herpesvirus (KSHV) establishes a latent infection, in which most viral genes are silenced except a few latent proteins such as latency-associated nuclear antigen (LANA). In latent viral chromatin, viral genes are poised to be transcribed, and KSHV LANA plays a major role in maintaining such transcription status. In the poised chromatins, LANA recruits cellular CHD4 (Chromodomain Helicase DNA binding protein 4) and suppresses inducible viral gene promoters. The CHD4 is known to regulate cell differentiation by restricting enhancer-promoter interactions and its mutation or overexpression deregulates the host cell transcription program and therefore associates with tumorigenesis. Here, we identified a putative CHD4 inhibitor from the LANA amino acid sequence from the LANA-CHD4 interaction surface. The small peptide interacts with CHD4 at its PHD domain with 14 nM KD (dissociation constant). The introduction of the peptide into the primary effusion lymphomas induces caspase-mediated CHD4 cleavage and subsequently triggered cell apoptosis and autophagy. A series of MTT assays demonstrated that the peptide preferentially killed lymphoma and leukemia cell lines at low micromolar concentrations, while peripheral mononuclear cells or adhesion cell lines were found to be more resistant to the peptide treatment. A monocyte cell differentiation model demonstrated that pre-treatment with the peptide at a low dose substantially enhanced transitioning into M2 macrophage (by reducing CHD4 occupancies from gene promoters), and globally altered the repertories of phorbol myristate acetate target genes in U937 cells. Finally, the PEL xenograft mouse model inhibited tumor growth without measurable side effects, and PEL cells isolated from xenograft tumors showed reduced CHD4 and LANA expression with terminally differentiated phenotype. We propose that the peptide isolated from the KSHV LANA sequence is biologically active and may function as a CHD4 inhibitor.
2024-03-01 | GSE228553 | GEO