Similar Datasets
Project description:The Epstein Barr virus (EBV) infects almost 95% of the population worldwide. While typically asymptomatic, EBV latent infection is associated with several malignancies of epithelial and lymphoid origin in immunocompromised individuals. In latently infected cells, the EBV genome persists as a chromatinized episome that expresses a limited set of viral genes in different patterns, referred to as latency types, which coincide with varying stages of infection and various malignancies. We have previously demonstrated that latency types correlate with differences in the composition and structure of the EBV episome. Several cellular factors, including the nuclear lamina, regulate chromatin composition and architecture. While the interaction of the viral genome with the nuclear lamina has been studied in the context of EBV lytic reactivation, the role of the nuclear lamina in controlling EBV latency has not been investigated. Here, we report that the nuclear lamina is an essential epigenetic regulator of the EBV episome. We observed that in B cells, EBV infection affects the composition of the nuclear lamina by inducing the expression of lamin A/C, but only in EBV+ cells expressing the Type III latency program. Using ChIP-Seq, we determined that lamin B1 and lamin A/C bind the EBV genome, and their binding correlates with deposition of the histone repressive mark H3K9me2. By RNA-Seq, we observed that knock-out of lamin A/C in B cells alters EBV gene expression. Our data indicate that the interaction between lamins and the EBV episome contributes to the epigenetic control of viral gene expression during latency, suggesting a restrictive function of the nuclear lamina as part of the host response against viral DNA entry into the nucleus.
| S-EPMC9009669 | biostudies-literature
Project description:Several cellular factors, including the nuclear lamina, regulate chromatin composition and architecture. While the interaction of the viral genome with the nuclear lamina has been studied in the context of EBV lytic reactivation, the role of the nuclear lamina in controlling EBV latency has not been investigated. Here, we report that the nuclear lamina is an essential epigenetic regulator of the EBV episome.
2022-03-18 | GSE198954 | GEO
Project description:Approximately 90% of the world population is infected with EBV and carries the virus in a silent, asymptomatic state for life. In immunocompromised individuals, EBV infection can cause B-cell transformation and malignancies. One approach to control EBV infectivity is by changing the expression of viral genes. We are interested in how epigenetics contributes to regulating the gene expression patterns adopted by EBV during latency. The host’s hijacking is a well know strategy adopted by viruses to modify the epigenome, the transcriptome and the proteome of the host with the aim to survive and remain silent in the host. We observed that in B cells, EBV infection mimics antigen-mediated activation, resulting in the induction of specific proteins named Lamin A/C. Lamins have multiple and central roles: they provide nuclear physical support, anchor the heterochromatin to the nuclear periphery and seem to play a role in several nuclear functions requiring the chromatin structure rearrangement. The interaction with lamins has already been studied in the context of EBV lytic reactivation, but their role in the control of the EBV latency states and as epigenetic regulators of different EBV genes expression profiles has not been investigated. The binding of the Lamin AC to important regulatory regions of EBV genome was assessed through ChIP-Seq, and gene expression (RNA-Seq) profiles were evaluated in wild type and Lamin AC KO cell lines. Differences in protein and RNA expressions in B cells activated by using both EBV and a simulation of the immune response were analyzed. Our data suggest two main conclusions: lamins might contribute to the epigenetic control of EBV genes expression during latency changing the interaction of the host structural proteins with key regulatory regions in the viral genome and a possible mechanism with who EBV modifies the nucleus and hijacks cellular mechanisms.
2022-04-08 | GSE198412 | GEO
Project description:Approximately 90% of the world population is infected with EBV and carries the virus in a silent, asymptomatic state for life. In immunocompromised individuals, EBV infection can cause B-cell transformation and malignancies. One approach to control EBV infectivity is by changing the expression of viral genes. We are interested in how epigenetics contributes to regulating the gene expression patterns adopted by EBV during latency. The host’s hijacking is a well know strategy adopted by viruses to modify the epigenome, the trascriptome and the proteome of the host with the aim to survive and remain silent in the host. We observed that in B cells, EBV infection mimics antigen-mediated activation, resulting in the induction of specific proteins named Lamin A/C. Lamins have multiple and central roles they: provide nuclear physical support; anchor the heterochromatin to the nuclear periphery and seem to play a role in several nuclear functions requing the chromatin structure rearrangement. The interaction with lamins has already been study in the context of EBV lytic reactivation, but their role in the control of the EBV latency states and as epigenetic regulators of different EBV genes expression profiles as not been investigated. The binding of the Lamin AC to important regulatory regions of EBV genome was assessed through ChIP-Seq and, and gene expression (RNA-Seq) profiles, were evaluated in wild type and Lamin AC KO cell lines. Differences in protein and RNA expressions in B cells activated by using both EBV and a simulation of the immune response were analyzed. Our data suggest two main conclusion: lamins might contribute to the epigenetic control of EBV genes expression during latency changing the interaction of the host structural proteins with key regulatory regions in the viral genome and a possible mechanism with who EBV modifies the nucleus and hijacks cellular mechanisms.
2022-03-11 | GSE181012 | GEO
Project description:Nuclear Lamina binds the EBV genome during latency and regulates viral gene expression
| PRJNA814988 | ENA
Project description:The Nuclear Lamina Binds the EBV Genome During Latency and Regulates Viral Gene Expression
| PRJNA817564 | ENA
Project description:Nuclear lamina binds the EBV genome during latency and regulates viral gene expression [Hi-C]
| PRJNA814994 | ENA
Project description:Nuclear Lamina binds the EBV genome during latency and regulates viral gene expression [RNA-seq]
| PRJNA750410 | ENA
Project description:The molecular basis for the formation of functional, higher-ordered macro-molecular domains is not completely known. The Kaposi's Sarcoma-Associated Herpesvirus (KSHV) genome forms a super-molecular domain structure during latent infection that is strictly dependent on the DNA binding of the viral nuclear antigen LANA to the viral terminal repeats (TR). LANA is known to form oligomeric structures that have been implicated in viral episome maintenance. In this study, we show that the LANA oligomerization interface is required for the formation of higher-order nuclear bodies that partially colocalize with DAXX, EZH2, H3K27me3, and ORC2 but not with PML. These nuclear bodies assemble at the periphery of condensed cellular chromosomes during mitotic cell division. We demonstrate that the LANA oligomerization interface contributes to the cooperative DNA binding at the viral TR and the recruitment of ORC to the viral episome. Oligomerization mutants failed to auto-regulate LANA/ORF73 transcription, and this correlated with the loss of a chromosome conformational DNA-loop between the TR and LANA promoter. Viral genomes with LANA oligomerization mutants were subject to genome rearrangements including the loss of subgenomic DNA. Our data suggests that LANA oligomerization drives stable binding to the TR and formation of an epigenetically stable chromatin architecture resulting in higher-order LANA nuclear bodies important for viral genome integrity and long-term episome persistence.
| S-EPMC6364946 | biostudies-literature
Project description:Epstein-Barr virus (EBV) controls gene expression to transform human B cells and maintain viral latency. High-throughput sequencing and crosslinking immunoprecipitation (HITS-CLIP) identified mRNA targets of 44 EBV and 310 human microRNAs (miRNAs) in Jijoye (Latency III) EBV-transformed B cells. While 25% of total cellular miRNAs are viral, only three viral mRNAs, all latent transcripts, are targeted. Thus, miRNAs do not control the latent/lytic switch by targeting EBV lytic genes. Unexpectedly, 90% of the 1664 human 3'-untranslated regions targeted by the 12 most abundant EBV miRNAs are also targeted by human miRNAs via distinct binding sites. Half of these are targets of the oncogenic miR-17?92 miRNA cluster and associated families, including mRNAs that regulate transcription, apoptosis, Wnt signalling, and the cell cycle. Reporter assays confirmed the functionality of several EBV and miR-17 family miRNA-binding sites in EBV latent membrane protein 1 (LMP1), EBV BHRF1, and host CAPRIN2 mRNAs. Our extensive list of EBV and human miRNA targets implicates miRNAs in the control of EBV latency and illuminates viral miRNA function in general.
| S-EPMC3343464 | biostudies-literature