Temporal Dynamics of HCMV Gene Expression in Lytic and Latent Infections
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ABSTRACT:
PROVIDER: PRJNA796314 | ENA |
REPOSITORIES: ENA
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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:We investigated the role of the chromatin remodeling protein ATRX on chromatin accessibility of HCMV genomes during the IE phase of lytic infections
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Project description:Purpose: to investigate expression of HCMV and cellular RNAs at early times post-infection in a lytic model
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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:Latent human cytomegalovirus (HCMV) in myeloid cells can be reactivated during cell differentiation and by inflammatory mediators. Expression level of immune regulator IL1R8 has been associated with the differentiation status of myeloid cells. As far, little is known about the role of IL1R8 in the association between reactivation of latent HCMV and differentiation of myeloid cells. To gain additional insights into IL1R8 and latency, a comparative transcriptome analysis was carried out through a unique bioinformatics approach that integrated IL1R8-correlated genes with differentially expressed genes to identify IL1R8-associated significant pathways. The Metascape pathway tool was utilized to perform enrichment analysis. The initial analysis revealed a significant inverse correlation between IL1R8 and viral counts (r = -0.42, z-score = -4.69) at single cell level in HCMV-infected monocytes at 4-14 days postinfection. In contrast to the majority of pathway analysis studies presenting unilateral up- or down-regulation, the current study discovered a number of bilaterally regulated key immune pathways in both lytic and latent infections. Notably, a ~3-fold predominant downregulation of the high-level adaptive immune system pathway was followed by a modestly predominant downregulation of mid-level Lymphocyte and low-level T cell activation pathways in latent infection. More interestingly, a unilateral upregulation pattern was identified exclusively in latent infection for Myeloid leukocyte activation, differentiation, and migration, in which upregulated genes were in concord with IL1R8 negatively correlated genes. The findings in the present study provided a comprehensive view of immunological alterations and a better understanding on the potential role of IL1R8 in the association between HCMV reactivation and myeloid cell differentiation in HCMV infection. The current study, for the first time, presented unique evidence supportive of a IL1R8-associated unilateral upregulation of myeloid leukocyte pathways in latent infection.
2021-04-26 | GSE173290 | GEO
Project description:Purpose: to investigate the role of the HCMV immediate early proteins in controlling the HCMV and cellular epigneomes during lytic infectioin
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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
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