ATRX reduces the accessibility of HCMV genomes during lytic infections
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE262839 | GEO | 2024/08/28
REPOSITORIES: GEO
Similar Datasets
Project description:Primary infection with Human cytomegalovirus (HCMV) results in a persistent lifelong infection due to its ability to establish latent infection. During productive HCMV infection, viral genes are expressed in a coordinated cascade that is characteristic of all herpesviruses and traditionally relies on the dependencies of viral genes on protein synthesis and viral DNA replication. In contrast, the transcriptional landscape associated with HCMV latency is still disputed and poorly understood. Here, we examine viral transcriptomic dynamics during the establishment of both productive and latent HCMV infections. These temporal measurements reveal that viral gene expression dynamics along productive infection and their dependencies on protein synthesis and viral DNA replication, do not fully align. This illustrates that the regulation of herpesvirus genes does not represent a simple sequential transcriptional cascade and surprisingly many viral genes are regulated by multiple independent modules. Using our improved classification of viral gene expression kinetics in conjunction with transcriptome-wide measurements of the effects of a wide array of chromatin modifiers, we unbiasedly show that a defining characteristic of latent cells is the unique repression of immediate early (IE) genes. In particular, we demonstrate that IE1 (a central IE protein) expression is the principal barrier for achieving a full productive cycle. Altogether, our findings provide an unbiased and elaborate definition of HCMV gene expression in lytic and latent infection states.
2022-03-29 | GSE193467 | GEO
Project description:Purpose: to investigate expression of HCMV and cellular RNAs at early times post-infection in a lytic model
2022-12-18 | GSE171520 | GEO
Project description:Purpose: to investigate occupancy of Pol II and H3K27Ac on the HCMV and cellular genomes at early times post-infection in a lytic model
2022-12-18 | GSE171512 | GEO
Project description:Temporal Dynamics of HCMV Gene Expression in Lytic and Latent Infections
| PRJNA796314 | ENA
Project description:Purpose: to investigate the role of the HCMV immediate early proteins in controlling the HCMV and cellular epigneomes during lytic infectioin
2022-12-21 | GSE171518 | GEO
Project description:Primary human GBM stem like cells were infected with HCMV TR strain (MOI=1) and treated with IE siRNA (a combination of oligos targeting IE1 and IE2 HCMV genes) 72 hours following siRNA treatment, RNA was harvested using Qiagen and divided equally for profiling using Affymetrix arrays and HCMV arrays.
2015-08-13 | GSE56750 | GEO
Project description:Human Cytomegalovirus (hCMV) infects a broad range of the population and establishes life-long latency in the infected individuals. Periodically the latently infected virus can reactivate and becomes a significant cause of morbidity and mortality in immunocompromised individuals. Upon reactivation, the repressive chromatin is remodeled to an active form, allowing viral lytic gene transcription, initiated by the expression of viral Immediate Early (IE) genes. During this process, a number of histone modification enzymes, including histone demethylases (HDMs), play important roles in driving IE expression, but the mechanisms involved are not fully understood. To get a better understanding of these mechanisms, we profiled this well-established CMV experimental latency-reactivation model based on TPA (12-O-Tetradecanoylphorbol-13-acetate) induced THP-1 differentiation, which recapitulates many key features of CMV latency and reactivation in vivo, including the important role of viral chromatin in controlling viral IE gene expression.
2017-03-27 | GSE97041 | GEO
Project description:Small, compact genomes confer a selective advantage to viruses, yet human cyto-megalovirus (HCMV) expresses the long non-coding RNAs (lncRNAs); RNA1.2, RNA2.7, RNA4.9, and RNA5.0. Little is known about the function of these lncRNAs in the virus life cycle. Here, we dissected the functional and molecular landscape of HCMV lncRNAs. We found that HCMV lncRNAs occupy ~30 % and 50~60 % of to-tal and poly(A)+ viral transcriptome, respectively, throughout virus life cycle. RNA1.2, RNA2.7, and RNA4.9, the three abundantly expressed lncRNAs, appear to be es-sential in all infection states. Among these three lncRNAs, depletion of RNA2.7 and RNA4.9 results in the greatest defect in maintaining latent reservoir and promoting lytic replication, respectively. Moreover, we delineated the global post-transcriptional nature of HCMV lncRNAs by nanopore direct RNA sequencing and interactome analysis. We revealed that the lncRNAs are modified with N⁶-methyladenosine (m6A) and interact with m6A readers in all infection states. In-depth analysis demonstrated that m6A machineries stabilize HCMV lncRNAs, which could account for the over-whelming abundance of viral lncRNAs. Our study lays the groundwork for under-standing the viral lncRNA–mediated regulation of host-virus interaction throughout the HCMV life cycle.
2022-11-16 | GSE217713 | GEO
Project description:Small, compact genomes confer a selective advantage to viruses, yet human cyto-megalovirus (HCMV) expresses the long non-coding RNAs (lncRNAs); RNA1.2, RNA2.7, RNA4.9, and RNA5.0. Little is known about the function of these lncRNAs in the virus life cycle. Here, we dissected the functional and molecular landscape of HCMV lncRNAs. We found that HCMV lncRNAs occupy ~30 % and 50~60 % of to-tal and poly(A)+ viral transcriptome, respectively, throughout virus life cycle. RNA1.2, RNA2.7, and RNA4.9, the three abundantly expressed lncRNAs, appear to be es-sential in all infection states. Among these three lncRNAs, depletion of RNA2.7 and RNA4.9 results in the greatest defect in maintaining latent reservoir and promoting lytic replication, respectively. Moreover, we delineated the global post-transcriptional nature of HCMV lncRNAs by nanopore direct RNA sequencing and interactome analysis. We revealed that the lncRNAs are modified with N⁶-methyladenosine (m6A) and interact with m6A readers in all infection states. In-depth analysis demonstrated that m6A machineries stabilize HCMV lncRNAs, which could account for the over-whelming abundance of viral lncRNAs. Our study lays the groundwork for under-standing the viral lncRNA–mediated regulation of host-virus interaction throughout the HCMV life cycle.
2022-11-16 | GSE217710 | GEO
Project description:During productive human cytomegalovirus (HCMV) infection, viral genes are expressed in a coordinated cascade that conventionally relies on the dependencies of viral genes on protein synthesis and viral DNA replication. By contrast, the transcriptional landscape of HCMV latency is poorly understood. Here, we examine viral gene expression dynamics during the establishment of both productive and latent HCMV infections. We redefine HCMV gene expression kinetics during productive infection and reveal that viral gene regulation does not represent a simple sequential cascade; many viral genes are regulated by multiple independent modules. Using our improved gene expression classification combined with transcriptome-wide measurements of the effects of a wide array of epigenetic inhibitors on viral gene expression during latency, we show that a defining feature of latency is the unique repression of immediate-early (IE) genes. Altogether, we recharacterize HCMV gene expression kinetics and reveal governing principles of lytic and latent gene expression.
| S-EPMC9035752 | biostudies-literature