scholarly journals Disruption of PML-Associated Nuclear Bodies by IE1 Correlates with Efficient Early Stages of Viral Gene Expression and DNA Replication in Human Cytomegalovirus Infection

Virology ◽  
2000 ◽  
Vol 274 (1) ◽  
pp. 39-55 ◽  
Author(s):  
Jin-Hyun Ahn ◽  
Gary S. Hayward
Keyword(s):  
Gene Expression ◽  
Dna Replication ◽  
Human Cytomegalovirus ◽  
Cytomegalovirus Infection ◽  
Viral Gene Expression ◽  
Nuclear Bodies ◽  
Viral Gene ◽  
Early Stages ◽  
Human Cytomegalovirus Infection

scholarly journals Human Cytomegalovirus Infection Causes Degradation of Sp100 Proteins That Suppress Viral Gene Expression

2011 ◽  
Vol 85 (22) ◽  
pp. 11928-11937 ◽  
Author(s):  
Y.-E. Kim ◽  
J.-H. Lee ◽  
E. T. Kim ◽  
H. J. Shin ◽  
S. Y. Gu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Cytomegalovirus ◽  
Cytomegalovirus Infection ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Human Cytomegalovirus Infection

scholarly journals Real-time Transcriptional Profiling of Cellular and Viral Gene Expression during Lytic Cytomegalovirus Infection

2012 ◽  
Vol 8 (9) ◽  
pp. e1002908 ◽  
Author(s):  
Lisa Marcinowski ◽  
Michael Lidschreiber ◽  
Lukas Windhager ◽  
Martina Rieder ◽  
Jens B. Bosse ◽  
...  
Keyword(s):  
Gene Expression ◽  
Real Time ◽  
Cytomegalovirus Infection ◽  
Transcriptional Profiling ◽  
Viral Gene Expression ◽  
Viral Gene

scholarly journals Human cytomegalovirus transcriptome activity differs during replication in human fibroblast, epithelial and astrocyte cell lines

2012 ◽  
Vol 93 (5) ◽  
pp. 1046-1058 ◽  
Author(s):  
James C. Towler ◽  
Bahram Ebrahimi ◽  
Brian Lane ◽  
Andrew J. Davison ◽  
Derrick J. Dargan
Keyword(s):  
Gene Expression ◽  
Human Cytomegalovirus ◽  
Growth Kinetics ◽  
Viral Gene Expression ◽  
Cell Types ◽  
Viral Gene ◽  
Genome Replication ◽  
Cell Type ◽  
Low Passage ◽  
Temporal Expression Pattern

Broad cell tropism contributes to the pathogenesis of human cytomegalovirus (HCMV), but the extent to which cell type influences HCMV gene expression is unclear. A bespoke HCMV DNA microarray was used to monitor the transcriptome activity of the low passage Merlin strain of HCMV at 12, 24, 48 and 72 h post-infection, during a single round of replication in human fetal foreskin fibroblast cells (HFFF-2s), human retinal pigmented epithelial cells (RPE-1s) and human astrocytoma cells (U373MGs). In order to correlate transcriptome activity with concurrent biological responses, viral cytopathic effect, growth kinetics and genomic loads were examined in the three cell types. The temporal expression pattern of viral genes was broadly similar in HFFF-2s and RPE-1s, but dramatically different in U373MGs. Of the 165 known HCMV protein-coding genes, 41 and 48 were differentially regulated in RPE-1s and U373MGs, respectively, compared with HFFF-2s, and 22 of these were differentially regulated in both RPE-1s and U373MGs. In RPE-1s, all differentially regulated genes were downregulated, but, in U373MGs, some were down- and others upregulated. Differentially regulated genes were identified among the immediate-early, early, early late and true-late viral gene classes. Grouping of downregulated genes according to function at landmark stages of the replication cycle led to the identification of potential bottleneck stages (genome replication, virion assembly, and virion maturation and release) that may account for cell type-dependent viral growth kinetics. The possibility that cell type-specific differences in expressed cellular factors are responsible for modulation of viral gene expression is discussed.

scholarly journals Lytic infection of permissive cells with human cytomegalovirus is regulated by an intrinsic ‘pre-immediate-early’ repression of viral gene expression mediated by histone post-translational modification

2009 ◽  
Vol 90 (10) ◽  
pp. 2364-2374 ◽  
Author(s):  
Ian J. Groves ◽  
Matthew B. Reeves ◽  
John H. Sinclair
Keyword(s):  
Gene Expression ◽  
Human Cytomegalovirus ◽  
Chromatin Structure ◽  
Viral Gene Expression ◽  
Lytic Infection ◽  
Immediate Early ◽  
Late Gene ◽  
Viral Gene ◽  
Gene Promoters ◽  
Late Gene Expression

Human cytomegalovirus (HCMV) lytic gene expression occurs in a regulated cascade, initiated by expression of the viral major immediate-early (IE) proteins. Transcribed from the major IE promoter (MIEP), the major IE genes regulate viral early and late gene expression. This study found that a substantial proportion of infecting viral genomes became associated with histones immediately upon infection of permissive fibroblasts at low m.o.i. and these histones bore markers of repressed chromatin. As infection progressed, however, the viral MIEP became associated with histone marks, which correlate with the known transcriptional activity of the MIEP at IE time points. Interestingly, this chromatin-mediated repression of the MIEP at ‘pre-IE’ times of infection could be overcome by inhibition of histone deacetylases, as well as by infection at high m.o.i., and resulted in a temporal advance of the infection cycle by inducing premature viral early and late gene expression and DNA replication. As well as the MIEP, and consistent with previous observations, the viral early and late promoters were also initially associated with repressive chromatin. However, changes in histone modifications around these promoters also occurred as infection progressed, and this correlated with the known temporal regulation of the viral early and late gene expression cascade. These data argue that the chromatin structure of all classes of viral genes are initially repressed on infection of permissive cells and that the chromatin structure of HCMV gene promoters plays an important role in regulating the time course of viral gene expression during lytic infection.

Cell-cycle-dependent localization of human cytomegalovirus UL83 phosphoprotein in the nucleolus and modulation of viral gene expression in human embryo fibroblasts in vitro

2011 ◽  
Vol 112 (1) ◽  
pp. 307-317 ◽  
Author(s):  
Maria-Cristina Arcangeletti ◽  
Isabella Rodighiero ◽  
Prisco Mirandola ◽  
Flora De Conto ◽  
Silvia Covan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Human Cytomegalovirus ◽  
Human Embryo ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Embryo Fibroblasts ◽  
Cycle Dependent

scholarly journals MicroRNA miR-21 Attenuates Human Cytomegalovirus Replication in Neural Cells by Targeting Cdc25a

2014 ◽  
Vol 89 (2) ◽  
pp. 1070-1082 ◽  
Author(s):  
Ya-Ru Fu ◽  
Xi-Juan Liu ◽  
Xiao-Jun Li ◽  
Zhang-zhou Shen ◽  
Bo Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Stem Cells ◽  
Birth Defects ◽  
Human Cytomegalovirus ◽  
Hcmv Infection ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Gene Products ◽  
Hcmv Replication

ABSTRACTCongenital human cytomegalovirus (HCMV) infection is a leading cause of birth defects, primarily manifesting as neurological disorders. HCMV infection alters expression of cellular microRNAs (miRs) and induces cell cycle arrest, which in turn modifies the cellular environment to favor virus replication. Previous observations found that HCMV infection reduces miR-21 expression in neural progenitor/stem cells (NPCs). Here, we show that infection of NPCs and U-251MG cells represses miR-21 while increasing the levels of Cdc25a, a cell cycle regulator and known target of miR-21. These opposing responses to infection prompted an investigation of the relationship between miR-21, Cdc25a, and viral replication. Overexpression of miR-21 in NPCs and U-251MG cells inhibited viral gene expression, genome replication, and production of infectious progeny, while shRNA-knockdown of miR-21 in U-251MG cells increased viral gene expression. In contrast, overexpression of Cdc25a in U-251MG cells increased viral gene expression and production of infectious progeny and overcame the inhibitory effects of miR-21 overexpression. Three viral gene products—IE1, pp71, and UL26—were shown to inhibit miR-21 expression at the transcriptional level. These results suggest that Cdc25a promotes HCMV replication and elevation of Cdc25a levels after HCMV infection are due in part to HCMV-mediated repression of miR-21. Thus, miR-21 is an intrinsic antiviral factor that is modulated by HCMV infection. This suggests a role for miR-21 downregulation in the neuropathogenesis of HCMV infection of the developing CNS.IMPORTANCEHuman cytomegalovirus (HCMV) is a ubiquitous pathogen and has very high prevalence among population, especially in China, and congenital HCMV infection is a major cause for birth defects. Elucidating virus-host interactions that govern HCMV replication in neuronal cells is critical to understanding the neuropathogenesis of birth defects resulting from congenital infection. In this study, we confirm that HCMV infection downregulates miR-21 but upregulates Cdc25a. Further determined the negative effects of cellular miRNA miR-21 on HCMV replication in neural progenitor/stem cells and U-251MG glioblastoma/astrocytoma cells. More importantly, our results provide the first evidence that miR-21 negatively regulates HCMV replication by targeting Cdc25a, a vital cell cycle regulator. We further found that viral gene products of IE1, pp71, and UL26 play roles in inhibiting miR-21 expression, which in turn causes increases in Cdc25a and benefits HCMV replication. Thus, miR-21 appears to be an intrinsic antiviral factor that represents a potential target for therapeutic intervention.

scholarly journals DNA Microarrays of the Complex Human Cytomegalovirus Genome: Profiling Kinetic Class with Drug Sensitivity of Viral Gene Expression

1999 ◽  
Vol 73 (7) ◽  
pp. 5757-5766 ◽  
Author(s):  
James Chambers ◽  
Ana Angulo ◽  
Dhammika Amaratunga ◽  
Hongqing Guo ◽  
Ying Jiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Cytomegalovirus ◽  
Dna Sequences ◽  
De Novo ◽  
Expression Profiles ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Viral Dna ◽  
Viral Protein Synthesis ◽  
Entire Genome

ABSTRACT We describe, for the first time, the generation of a viral DNA chip for simultaneous expression measurements of nearly all known open reading frames (ORFs) in the largest member of the herpesvirus family, human cytomegalovirus (HCMV). In this study, an HCMV chip was fabricated and used to characterize the temporal class of viral gene expression. The viral chip is composed of microarrays of viral DNA prepared by robotic deposition of oligonucleotides on glass for ORFs in the HCMV genome. Viral gene expression was monitored by hybridization to the oligonucleotide microarrays with fluorescently labelled cDNAs prepared from mock-infected or infected human foreskin fibroblast cells. By using cycloheximide and ganciclovir to block de novo viral protein synthesis and viral DNA replication, respectively, the kinetic classes of array elements were classified. The expression profiles of known ORFs and many previously uncharacterized ORFs provided a temporal map of immediate-early (α), early (β), early-late (γ1), and late (γ2) genes in the entire genome of HCMV. Sequence compositional analysis of the 5′ noncoding DNA sequences of the temporal classes, performed by using algorithms that automatically search for defined and recurring motifs in unaligned sequences, indicated the presence of potential regulatory motifs for β, γ1, and γ2 genes. In summary, these fabricated microarrays of viral DNA allow rapid and parallel analysis of gene expression at the whole viral genome level. The viral chip approach coupled with global biochemical and genetic strategies should greatly speed the functional analysis of established as well as newly discovered large viral genomes.

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