KSHV/EBV co-infection and tumorigenesis
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB18662 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR2029480_1.fastq.gz | Fastqsanger.gz | |||
| ERR2029480_2.fastq.gz | Fastqsanger.gz | |||
| ERR2029490_1.fastq.gz | Fastqsanger.gz | |||
| ERR2029490_2.fastq.gz | Fastqsanger.gz | |||
| ERR2029500_1.fastq.gz | Fastqsanger.gz |
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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: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: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
Project description:The establishment of latency is an essential step for the life-long persistent infection and pathogenesis of KaposiM-bM-^@M-^Ys sarcoma-associated herpesvirus (KSHV). While the KSHV genome is chromatin-free in the virions, the viral DNA in latently infected cells has a chromatin structure that is characterized by a specific pattern of activating and repressive histone modifications that ultimately promote latent gene expression while suppressing lytic gene expression. To investigate the molecular events involved in the establishment of the latent chromatin structure during the pre-latency phase of KSHV infection, we performed a comprehensive epigenetic study to analyze the recruitment of chromatin regulatory factors onto the KSHV genome at various time-points following de novo infection of SLK and TIME cells. This showed that the KSHV genome undergoes a biphasic chromatinization following de novo infection. Initially, a transcriptionally active chromatin (euchromatin), characterized by high levels of the H3K4me3 and acetylated H3K27 (H3K27ac) activating histone marks, was deposited on the viral episome and was accompanied by the temporary induction of a limited number of lytic genes. Interestingly, transient expression of the RTA protein facilitated the increases of H3K4me3 and H3K27ac occupancy on the KSHV episome during de novo infection. Between 24-72 hours post-infection, as the levels of these activating histone marks declined on the KSHV genome, the levels of the repressive H3K27me3 and H2AK119ub histone marks increased concomitantly with the decline of lytic gene expression. Importantly, this transition to heterochromatin was dependent on both the Polycomb Repressive Complex 2 and 1. In contrast, upon infection of human gingiva-derived epithelial cells, the KSHV genome underwent a continuously transcription-active euchromatinization, resulting in efficient lytic gene expression. Our data demonstrate that the KSHV genome undergoes a temporally ordered biphasic euchromatin-to-heterochromatin transition in endothelial cells, leading to latent infection, whereas KSHV preferentially adopts a transcriptionally active euchromatin in oral epithelial cells, resulting in lytic gene expression. Our results suggest that the differential epigenetic modification of the KSHV genome in distinct cell types is a potential determining factor for latent infection vs. lytic replication of KSHV. Please see above. 16 hybridizations: ChIP and Input DNA
2014-01-01 | E-GEOD-51660 | biostudies-arrayexpress
Project description:Epstein-Barr virus (EBV) Rta is a latent-lytic molecular switch evolutionarily conserved in all gamma-herpesviruses. In previous studies, doxycycline-inducible Rta was shown to potently produce an irreversible G1 arrest followed by cellular senescence in 293 cells. Here, we demonstrate that in this system the inducible Rta not only reactivates resident genome of EBV but also that of Kaposi’s sarcoma-associated herpesvirus (KSHV), to similar efficiency. However, Rta-induced senescence program was terminated by the robust viral lytic cycle replication that eventually caused cell death. Furthermore, prior to the abrupt expression of immediate-early protein (EBV BZLF1 or KSHV RTA), Rta simultaneously down-regulates cell cycle activators (c-Myc, CDK6, CCND2) and up-regulates senescence-related genes (p21, 14-3-3s). Since Rta is a viral immediate-early transcriptional activator, it is envisioned that during the initial stage of viral reactivation, Rta may engage to modulate the host transcriptome, to halt cell cycle progression, and to maintain an ideal environment for manufacturing infectious virions. Refer to individual Series. This SuperSeries is composed of the following subset Series: GSE24585: Expression profiling of host genes modulated by Epstein-Barr virus (EBV) Rta in HEK293 cells GSE24586: Expression profiling of host genes modulated by Epstein-Barr virus Rta in nasopharyngeal carcinoma cells
2011-03-31 | E-GEOD-24587 | biostudies-arrayexpress
Project description:The nucleus is a highly structured environment containing multiple membrane-less bodies formed through liquid-liquid phase separation. These provide spatial separation and concentration of specific biomolecules enabling efficient and discrete processes to occur which regulate gene expression. One such nuclear body, paraspeckles, are comprised of multiple paraspeckle proteins (PSPs) built around the architectural RNA, NEAT1_2. Paraspeckle function is yet to be fully elucidated but has been implicated in a variety of developmental and disease scenarios. We demonstrate that Kaposi’s sarcoma-associated herpesvirus (KSHV) drives formation of structurally distinct paraspeckles with a dramatically increased size and altered protein composition that are essential for productive lytic replication. We highlight these virus-induced paraspeckle-like structures form adjacent to virus replication centres, functioning as RNA processing hubs for both viral and cellular transcripts during infection. Notably, we reveal that PSP sequestration into virus-induced paraspeckle-like structures results in increased genome instability during both KSHV and Epstein Barr virus (EBV) infection, implicating their formation in virus-mediated tumorigenesis.
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Project description:The establishment of latency is an essential step for the life-long persistent infection and pathogenesis of Kaposi’s sarcoma-associated herpesvirus (KSHV). While the KSHV genome is chromatin-free in the virions, the viral DNA in latently infected cells has a chromatin structure that is characterized by a specific pattern of activating and repressive histone modifications that ultimately promote latent gene expression while suppressing lytic gene expression. To investigate the molecular events involved in the establishment of the latent chromatin structure during the pre-latency phase of KSHV infection, we performed a comprehensive epigenetic study to analyze the recruitment of chromatin regulatory factors onto the KSHV genome at various time-points following de novo infection of SLK and TIME cells. This showed that the KSHV genome undergoes a biphasic chromatinization following de novo infection. Initially, a transcriptionally active chromatin (euchromatin), characterized by high levels of the H3K4me3 and acetylated H3K27 (H3K27ac) activating histone marks, was deposited on the viral episome and was accompanied by the temporary induction of a limited number of lytic genes. Interestingly, transient expression of the RTA protein facilitated the increases of H3K4me3 and H3K27ac occupancy on the KSHV episome during de novo infection. Between 24-72 hours post-infection, as the levels of these activating histone marks declined on the KSHV genome, the levels of the repressive H3K27me3 and H2AK119ub histone marks increased concomitantly with the decline of lytic gene expression. Importantly, this transition to heterochromatin was dependent on both the Polycomb Repressive Complex 2 and 1. In contrast, upon infection of human gingiva-derived epithelial cells, the KSHV genome underwent a continuously transcription-active euchromatinization, resulting in efficient lytic gene expression. Our data demonstrate that the KSHV genome undergoes a temporally ordered biphasic euchromatin-to-heterochromatin transition in endothelial cells, leading to latent infection, whereas KSHV preferentially adopts a transcriptionally active euchromatin in oral epithelial cells, resulting in lytic gene expression. Our results suggest that the differential epigenetic modification of the KSHV genome in distinct cell types is a potential determining factor for latent infection vs. lytic replication of KSHV. Please see above.
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Project description:Most humans are infected with Epstein-Barr virus (EBV), a cancer-causing virus. While EBV generally persists silently in B lymphocytes, periodic lytic (re-)activation of latent virus is central to its life cycle and to most EBV-related diseases. However, a substantial fraction of EBV-infected B cells and tumor cells in a population is refractory to lytic activation. This resistance to lytic activation directly and profoundly impacts viral persistence and effectiveness of oncolytic therapy for EBV+ cancers. To identify the mechanisms that underlie susceptibility to EBV-lytic activation, we used host protein-expression profiling of separated-lytic and -refractory cells.
2016-04-27 | PXD001838 | Pride
Project description:Epstein-Barr virus (EBV) Rta is a latent-lytic molecular switch evolutionarily conserved in all gamma-herpesviruses. In previous studies, doxycycline-inducible Rta was shown to potently produce an irreversible G1 arrest followed by cellular senescence in 293 cells. Here, we demonstrate that in this system the inducible Rta not only reactivates resident genome of EBV but also that of Kaposi’s sarcoma-associated herpesvirus (KSHV), to similar efficiency. However, Rta-induced senescence program was terminated by the robust viral lytic cycle replication that eventually caused cell death. Furthermore, prior to the abrupt expression of immediate-early protein (EBV BZLF1 or KSHV RTA), Rta simultaneously down-regulates cell cycle activators (c-Myc, CDK6, CCND2) and up-regulates senescence-related genes (p21, 14-3-3s). Since Rta is a viral immediate-early transcriptional activator, it is envisioned that during the initial stage of viral reactivation, Rta may engage to modulate the host transcriptome, to halt cell cycle progression, and to maintain an ideal environment for manufacturing infectious virions. This SuperSeries is composed of the SubSeries listed below.
2011-03-31 | GSE24587 | GEO