Global host gene expression changes in KSHV+ PEL cells upon KSHV reactivation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE123898 | GEO | 2019/01/09
REPOSITORIES: GEO
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Project description:Chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) analysis was performed during Kaposi's sarcoma-associated herpesvirus (KSHV) reactivation in KSHV+ recombinant primary effusion B-cell lymphoma cells (PEL). RTA binding sites were identified genome-wide in a recombinant PEL cell line called TRExBCBL1-3xFLAG-RTA cells at 12 hours post-induction (hpi) of RTA expression.
2019-01-09 | GSE123897 | GEO
Project description:Primari effusion lymphoma are (PEL) patient-derived transformed B-cells harboring latent Kaposi's sarcoma-associated herpesvirus (KSHV). The treatment of PEL cells with valproic acid (VA) leads to reactivation of KSHV and viral lytic replication. The aim of this project is to evaluate the effect of KSHV lytic infection on expression of the host transcriptome.
2021-11-08 | GSE179727 | GEO
Project description:Primary effusion lymphoma (PEL) is a rare B-cell malignancy that originates from B cells latently infected with Kaposi’s sarcoma-associated herpesvirus (KSHV, also known as human herpesvirus-8, HHV8). Our previous data indicated that several exogenous ceramide and dh-ceramide species, such as C18-Cer and dhC16-Cer, also displayed effective anti-cancer activities for KSHV+ PEL in vitro and in vivo. However, the underlying mechanisms for exogenous ceramide “killing” PEL cells still require further investigation, which will be helpful to better understand PEL pathogenesis and identify more potential therapeutic targets. In the current study, we used Illumina microarray to determine the altered gene profile in KSHV+ PEL cell-line, BCBL-1 exposure to dhC16-Cer.
2017-06-10 | GSE90038 | GEO
Project description:The RIG-I like receptors (RLRs) RIG-I and MDA5 are cytosolic RNA helicases best characterized as restriction factors for RNA viruses. However, evidence suggests RLRs participate in innate immune recognition of other pathogens, including DNA viruses. Kaposi's sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus and the etiological agent of Kaposi's sarcoma and primary effusion lymphoma (PEL). We demonstrate that RIG-I and MDA5 restrict KSHV lytic reactivation in PEL. By performing fRIP-Seq, we define the in vivo RLR substrates and demonstrate that RIG-I and MDA5-mediated restriction is facilitated exclusively by the recognition of host-derived RNAs.
2018-10-11 | GSE116650 | GEO
Project description:Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of primary effusion lymphoma (PEL). All PEL cell lines are infected with KSHV, and 70% are co-infected with Epstein-Barr Virus (EBV). KSHV reactivation from latency requires promoter-specific transactivation by the KSHV Rta protein through interactions with RBP-Jk (CSL), the cellular DNA binding component of the Notch signal transduction pathway. EBV transformation of primary B cells requires EBV nuclear antigen (EBNA)-2 to interact with RBP-Jk to direct the latent viral and cellular gene expression program. Although KSHV Rta and EBV EBNA-2 both require RBP-Jk for transactivation, previous studies have suggested that RBP-Jk-dependent transactivators do not function identically. We have found that the EBV latent protein LMP-1 is expressed in less than 5% of KSHV+/EBV+ PEL cells, but is induced in an Rta-dependent fashion when KSHV reactivates. KSHV Rta transactivates the EBV latency promoters in an RBP-Jk-dependent fashion and forms a ternary complex with RBP-Jk on the promoters. In B cells that are conditionally transformed by EBV alone, we show that KSHV Rta complements a short-term EBNA2 growth deficiency in an autocrine/paracrine manner. Complementaton of EBNA2-deficiency by Rta depends on RBP-Jk and LMP-1, and Rta transactivation is required for optimal growth of KSHV+/EBV+ PEL lines. Our data suggest that Rta can contribute to EBV-driven cellular growth by transactivating RBP-Jk-dependent EBV latency genes. However, our data also suggest that EBNA2 and Rta induce distinct alterations in the cellular proteomes that contribute to growth of infected cells.
2010-12-31 | GSE21375 | GEO
Project description:Primary effusion lymphoma (PEL) is an aggressive subtype of non-Hodgkin lymphoma caused by Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Currently, treatment options for patients with PEL are limited. Oncolytic viruses have been engineered as anticancer agents and have recently shown increased therapeutic promise. Similarly, lytic activation of endogenous viruses from latently infected tumor cells can also be applied as a cancer therapy. In theory, such a therapeutic strategy would induce oncolysis by viral replication, while simultaneously stimulating an immune response to viral lytic cycle antigens. We examined the combination of the FDA-approved drug ingenol-3-angelate (PEP005) with epigenetic drugs as a rational therapeutic approach for KSHV-mediated malignancies. JQ1, a bromodomain and extra terminal (BET) protein inhibitor, in combination with PEP005, not only robustly induced KSHV lytic replication, but also inhibited IL6 production from PEL cells. Using the dosages of these agents that was found to be effective in reactivating HIV (as a means to clear latent virus with highly active antiretroviral therapy), we were able to inhibit PEL growth in vitro and delay tumor growth in a PEL xenograft tumor model. KSHV reactivation was mediated by activation of NF-kB pathway by PEP005, which led to increased occupancy of RNA polymerase II onto the KSHV 33 genome. RNA-sequencing analysis further revealed cellular targets of PEP005, JQ1, and the synergistic effects of both. Thus, combination of PEP005 with a BET inhibitor may be considered as a rational therapeutic approach for the treatment of PEL.
2017-10-24 | GSE103395 | GEO
Project description:Herpesvirus latency is generally thought to be governed by epigenetic modifications, but the dynamics of viral chromatin at early timepoints of latent infection are poorly understood. Here, we report a comprehensive spatial and temporal analysis of epigenetic modifications during latent infection with Kaposi's sarcoma associated herpesvirus (KSHV), the etiologic agent of Kaposi's sarcoma and primary effusion lymphoma (PEL). Using high resolution tiling microarrays in conjunction with immunprecipitation of methylated DNA (MeDIP) and modified histones (ChIP), we have determined global patterns of epigenetic modifications across the KSHV genome in several tumor-derived cell lines as well as de novo infected endothelial cells, revealing highly distinct landscapes of epigenetic modifications associated with latent KSHV infection. We find that KSHV genomes are subject to profound methylation at CpG dinucleotides, leading to the establishment of characteristic global DNA methylation patterns. However, such patterns evolved slowly and thus are unlikely to govern latency early during the infection process. In contrast, we observed that latent histone modification patterns were rapidly established upon a de novo infection. Our analysis furthermore demonstrates that such patterns are not characterized by the absence of activating histone modifications, since both H3K9/K14-ac and H3K4-me3 marks were prominently detected at several loci, including the promoter of the lytic cycle transactivator Rta. While these regions were furthermore largely devoid of the constitutive heterochromatin marker H3K9-me3, we observed rapid and widespread deposition of H3K27-me3 across latent KSHV genomes, a bivalent modification which is able to repress transcription despite of the simultaneous presence of activating marks. Our findings suggest that the epigenetic patterns identified here induce a poised state of repression during viral latency, which can be rapidly reversed once the lytic cycle is induced. This dataset contains our MeDIP data; the ChIP-on-chip data are deposited in a separate dataset.
2010-06-07 | GSE19905 | GEO
Project description:Primary effusion lymphoma (PEL) is caused by Kaposi's sarcoma-associated herpesvirus (KSHV) and frequently also harbors Epstein-Barr virus (EBV). The expression of KSHV- and, often, EBV-encoded microRNAs (miRNAs) in PELs suggests a role for these miRNAs in viral latency and lymphomagenesis. Here we report the direct and transcriptome-wide identification of miRNA target sites for all miRNAs expressed in PEL cell lines. The resulting dataset revealed that KSHV miRNAs directly target more than 2000 cellular mRNAs encoding proteins that function in pathways with relevance to KSHV pathogenesis. Moreover, ~50% of these mRNAs are also targeted by EBV miRNAs, via distinct binding sites. In addition to a known viral analog of miR-155, we show that KSHV encodes a viral miRNA that mimics cellular miR-142-3p function. In summary, these experiments identify an extensive list of mRNAs targeted by KSHV miRNAs and indicate that these are likely to strongly influence viral replication and pathogenesis. small RNA sequencing, 3 samples Ago2 (EIF2C2) PAR-CLIP, 2 samples
2011-11-16 | E-GEOD-32109 | biostudies-arrayexpress
Project description:Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of primary effusion lymphoma (PEL). All PEL cell lines are infected with KSHV, and 70% are co-infected with Epstein-Barr Virus (EBV). KSHV reactivation from latency requires promoter-specific transactivation by the KSHV Rta protein through interactions with RBP-Jk (CSL), the cellular DNA binding component of the Notch signal transduction pathway. EBV transformation of primary B cells requires EBV nuclear antigen (EBNA)-2 to interact with RBP-Jk to direct the latent viral and cellular gene expression program. Although KSHV Rta and EBV EBNA-2 both require RBP-Jk for transactivation, previous studies have suggested that RBP-Jk-dependent transactivators do not function identically. We have found that the EBV latent protein LMP-1 is expressed in less than 5% of KSHV+/EBV+ PEL cells, but is induced in an Rta-dependent fashion when KSHV reactivates. KSHV Rta transactivates the EBV latency promoters in an RBP-Jk-dependent fashion and forms a ternary complex with RBP-Jk on the promoters. In B cells that are conditionally transformed by EBV alone, we show that KSHV Rta complements a short-term EBNA2 growth deficiency in an autocrine/paracrine manner. Complementaton of EBNA2-deficiency by Rta depends on RBP-Jk and LMP-1, and Rta transactivation is required for optimal growth of KSHV+/EBV+ PEL lines. Our data suggest that Rta can contribute to EBV-driven cellular growth by transactivating RBP-Jk-dependent EBV latency genes. However, our data also suggest that EBNA2 and Rta induce distinct alterations in the cellular proteomes that contribute to growth of infected cells. EREB2-5 cells were transfected and grown in the presence or absence of β-estradiol, as described. Seven days post-transfection, protein extracts were prepared, and 200 ugs. of each were analyzed using the RayBio Human Apoptosis Antibody Array Kit (RayBiotech) as per manufacturers suggestions. The membranes were exposed to autoradiography film for different times to detect the chemiluminescent signals. Images with signals in linear range were quantitated using the program ImageJ [59]. For each membrane, signals from the negative control spots were averaged, and then subtracted from each of the other spots. A signal was considered valid if its value exceeded both its average local background, and the average of all valid negative control values. Valid signals were normalized using the positive control spots (for cellular BID protein). Fold change in signals for each spot were quantitated by dividing by the valid signals for each corresponding spot on the minus β-estradiol membrane. Average fold change, and standard deviation, were calculated for each protein.
2010-12-31 | E-GEOD-21375 | biostudies-arrayexpress
Project description:KSHV-related primary effusion lymphoma is mostly seen in immunocompromised individuals such as HIV+ patients, who frequently suffering polymicrobial infections including different opportunistic pathogens. It is interesting to explore the host gene profile in PEL altered by bacterial quorum sensing molecules, the key systems regulating virulence factors in many bacteria.
2018-05-22 | GSE110172 | GEO