scholarly journals Regulation of Gene Expression in Primate Polyomaviruses

2009 ◽  
Vol 83 (21) ◽  
pp. 10846-10856 ◽  
Author(s):  
Martyn K. White ◽  
Mahmut Safak ◽  
Kamel Khalili
Keyword(s):  
Gene Expression ◽  
Jc Virus ◽  
Regulation Of Gene Expression ◽  
T Antigen ◽  
Bk Virus ◽  
Viral Gene ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Karolinska Institute ◽  
Human Polyomaviruses

ABSTRACT Polyomaviruses are a growing family of small DNA viruses with a narrow tropism for both the host species and the cell type in which they productively replicate. Species host range may be constrained by requirements for precise molecular interactions between the viral T antigen, host replication proteins, including DNA polymerase, and the viral origin of replication, which are required for viral DNA replication. Cell type specificity involves, at least in part, transcription factors that are necessary for viral gene expression and restricted in their tissue distribution. In the case of the human polyomaviruses, BK virus (BKV) replication occurs in the tubular epithelial cells of the kidney, causing nephropathy in kidney allograft recipients, while JC virus (JCV) replication occurs in the glial cells of the central nervous system, where it causes progressive multifocal leukoencephalopathy. Three new human polyomaviruses have recently been discovered: MCV was found in Merkel cell carcinoma samples, while Karolinska Institute Virus and Washington University Virus were isolated from the respiratory tract. We discuss control mechanisms for gene expression in primate polyomaviruses, including simian vacuolating virus 40, BKV, and JCV. These mechanisms include not only modulation of promoter activities by transcription factor binding but also enhancer rearrangements, restriction of DNA methylation, alternate early mRNA splicing, cis-acting elements in the late mRNA leader sequence, and the production of viral microRNA.

scholarly journals JC virus promoter/enhancers contain TATA box-associated Spi-B-binding sites that support early viral gene expression in primary astrocytes

2012 ◽  
Vol 93 (3) ◽  
pp. 651-661 ◽  
Author(s):  
Leslie J. Marshall ◽  
Lisa D. Moore ◽  
Matthew M. Mirsky ◽  
Eugene O. Major
Keyword(s):  
Gene Expression ◽  
Binding Sites ◽  
Jc Virus ◽  
Viral Gene Expression ◽  
Antigen Expression ◽  
T Antigen ◽  
Viral Gene ◽  
Large T Antigen ◽  
Viral Promoter ◽  
The Brain

JC virus (JCV) is the aetiological agent of the demyelinating disease progressive multifocal leukoencephalopathy, an AIDS defining illness and serious complication of mAb therapies. Initial infection probably occurs in childhood. In the working model of dissemination, virus persists in the kidney and lymphoid tissues until immune suppression/modulation causes reactivation and trafficking to the brain where JCV replicates in oligodendrocytes. JCV infection is regulated through binding of host factors such as Spi-B to, and sequence variation in the non-coding control region (NCCR). Although NCCR sequences differ between sites of persistence and pathogenesis, evidence suggests that the virus that initiates infection in the brain disseminates via B-cells derived from latently infected haematopoietic precursors in the bone marrow. Spi-B binds adjacent to TATA boxes in the promoter/enhancer of the PML-associated JCV Mad-1 and Mad-4 viruses but not the non-pathogenic, kidney-associated archetype. The Spi-B-binding site of Mad-1/Mad-4 differs from that of archetype by a single nucleotide, AAAAGGGAAGGGA to AAAAGGGAAGGTA. Point mutation of the Mad-1 Spi-B site reduced early viral protein large T-antigen expression by up to fourfold. Strikingly, the reverse mutation in the archetype NCCR increased large T-antigen expression by 10-fold. Interestingly, Spi-B protein binds the NCCR sequence flanking the viral promoter/enhancer, but these sites are not essential for early viral gene expression. The effect of mutating Spi-B-binding sites within the JCV promoter/enhancer on early viral gene expression strongly suggests a role for Spi-B binding to the viral promoter/enhancer in the activation of early viral gene expression.

scholarly journals Nanopore Assay Reveals Cell-type-dependent Gene Expression of Indiana Vesiculovirus and Differential Host Cell Response

2021 ◽  
Author(s):  
Balázs Kakuk ◽  
András Attila Kiss ◽  
Gábor Torma ◽  
Zsolt Csabai ◽  
István Prazsák ◽  
...  
Keyword(s):  
Gene Expression ◽  
Time Course ◽  
Expression Patterns ◽  
Viral Gene Expression ◽  
Fibroblast Cell ◽  
Economic Loss ◽  
Viral Gene ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Vesicular Stomatitis

Indiana Vesiculovirus (IVV; formerly as Vesicular stomatitis virus and Vesicular stomatitis Indiana virus) causes a disease in livestock that is very similar to the foot and mouth disease thereby an outbreak may lead to significant economic loss. Long-read sequencing (LRS) -based approaches revealed a hidden complexity of the transcriptomes in several viruses already. This technique was utilized already for the sequencing of the IVV genome, but our study is the first for the application of this technique for the profiling of IVV transcriptome. Since LRS is able to sequence full-length RNA molecules, and thereby providing more accurate annotation of the transcriptomes than the traditional short-read sequencing methods. The objectives of this study were to assemble the complete transcriptome of using nanopore sequencing, to ascertain cell-type specificity and dynamics of viral gene expression and to evaluate host gene expression changes induced by the viral infection. We carried out a time-course analysis of IVV gene expression in human glioblastoma and primate fibroblast cell lines using a nanopore-based LRS approach and applied both amplified and direct cDNA sequencing, as well as cap-selection for a fraction of samples. Our investigations revealed that, although the IVV genome is simple, it generates a relative complex transcriptomic architecture. In this study, we also demonstrated that IVV transcripts vary in structure and exhibit differential gene expression patterns in the two examined cell types.

scholarly journals Nanopore Assay Reveals Cell-Type-Dependent Gene Expression of Vesicular Stomatitis Indiana Virus and Differential Host Cell Response

Pathogens ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1196
Author(s):  
Balázs Kakuk ◽  
András Attila Kiss ◽  
Gábor Torma ◽  
Zsolt Csabai ◽  
István Prazsák ◽  
...  
Keyword(s):  
Gene Expression ◽  
Time Course ◽  
Expression Patterns ◽  
Viral Gene Expression ◽  
Fibroblast Cell ◽  
Economic Loss ◽  
Viral Gene ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Vesicular Stomatitis

Vesicular stomatitis Indiana virus (VSIV) of genus Vesiculovirus, species IndianaVesiculovirus (formerly as Vesicular stomatitis virus, VSV) causes a disease in livestock that is very similar to the foot and mouth disease, thereby an outbreak may lead to significant economic loss. Long-read sequencing (LRS) -based approaches already reveal a hidden complexity of the transcriptomes in several viruses. This technique has been utilized for the sequencing of the VSIV genome, but our study is the first for the application of this technique for the profiling of the VSIV transcriptome. Since LRS is able to sequence full-length RNA molecules, it thereby provides more accurate annotation of the transcriptomes than the traditional short-read sequencing methods. The objectives of this study were to assemble the complete transcriptome of using nanopore sequencing, to ascertain cell-type specificity and dynamics of viral gene expression, and to evaluate host gene expression changes induced by the viral infection. We carried out a time-course analysis of VSIV gene expression in human glioblastoma and primate fibroblast cell lines using a nanopore-based LRS approach and applied both amplified and direct cDNA sequencing (as well as cap-selection) for a fraction of samples. Our investigations revealed that, although the VSIV genome is simple, it generates a relatively complex transcriptomic architecture. In this study, we also demonstrated that VSIV transcripts vary in structure and exhibit differential gene expression patterns in the two examined cell types.

scholarly journals Quantification of Human Polyomaviruses JC Virus and BK Virus by TaqMan Quantitative PCR and Comparison to Other Water Quality Indicators in Water and Fecal Samples

2009 ◽  
Vol 75 (11) ◽  
pp. 3379-3388 ◽  
Author(s):  
Shannon M. McQuaig ◽  
Troy M. Scott ◽  
Jerzy O. Lukasik ◽  
John H. Paul ◽  
Valerie J. Harwood
Keyword(s):  
Water Quality ◽  
Quantitative Pcr ◽  
Jc Virus ◽  
The United States ◽  
T Antigen ◽  
Bk Virus ◽  
Qpcr Assay ◽  
Gene Copies ◽  
Bodies Of Water ◽  
Human Polyomaviruses

ABSTRACT In the United States, total maximum daily load standards for bodies of water that do not meet bacterial water quality standards are set by each state. The presence of human polyomaviruses (HPyVs) can be used as an indicator of human-associated sewage pollution in these waters. We have developed and optimized a TaqMan quantitative PCR (QPCR) assay based on the conserved T antigen to both quantify and simultaneously detect two HPyVs; JC virus and BK virus. The QPCR assay was able to consistently quantify ≥10 gene copies per reaction and is linear over 5 orders of magnitude. HPyVs were consistently detected in human waste samples (57 of 64) and environmental waters with known human fecal contamination (5 of 5) and were not amplified in DNA extracted from 127 animal waste samples from 14 species. HPyV concentrations in sewage decreased 81.2 and 84.2% over 28 days incubation at 25 and 35°C, respectively. HPyVs results were compared to Escherichia coli, fecal coliform, and enterococci concentrations and the presence of three other human-associated microbes: Bacteroidetes, Methanobrevibacter smithii, and adenovirus. HPyVs were the most frequently detected of these in human and contaminated environmental samples and were more human specific than the Bacteroidetes (HF183) or M. smithii. HPyVs and M. smithii more closely mimicked the persistence of adenovirus in sewage than the other microbes. The use of this rapid and quantitative assay in water quality research could help regulatory agencies to identify sources of water pollution for improved remediation of contaminated waters and ultimately protect humans from exposure to pathogens.

Specificity of gene expression in adipocytes

1985 ◽  
Vol 5 (2) ◽  
pp. 419-421
Author(s):  
K M Zezulak ◽  
H Green
Keyword(s):  
Gene Expression ◽  
Cell Types ◽  
Cell Type ◽  
3T3 Cells ◽  
Cell Type Specificity ◽  
Number Of Genes ◽  
Enhanced Expression ◽  
Adipose Cells ◽  
Distinctive Phenotype

During the differentiation of preadipose 3T3 cells into adipose cells, the mRNAs for three proteins increase strikingly in abundance. To determine the degree of cell-type specificity in the expression of these mRNAs, we estimated their abundances in several nonadipose tissues of the mouse. None of these mRNAs was strictly confined to adipocytes, but the ensemble of three mRNAs was rather specific to adipocytes. Insofar as is revealed by these three markers, the distinctive phenotype of adipocytes is the result of the enhanced expression of a number of genes, none of which is completely silent in all other cell types.

scholarly journals A scalable platform for the development of cell-type-specific viral drivers

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Sinisa Hrvatin ◽  
Christopher P Tzeng ◽  
M Aurel Nagy ◽  
Hume Stroud ◽  
Charalampia Koutsioumpa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heterologous Gene Expression ◽  
High Specificity ◽  
Cell Types ◽  
Regulatory Elements ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Cell Type Specific ◽  
The Many ◽  
Dna Regulatory Elements

Enhancers are the primary DNA regulatory elements that confer cell type specificity of gene expression. Recent studies characterizing individual enhancers have revealed their potential to direct heterologous gene expression in a highly cell-type-specific manner. However, it has not yet been possible to systematically identify and test the function of enhancers for each of the many cell types in an organism. We have developed PESCA, a scalable and generalizable method that leverages ATAC- and single-cell RNA-sequencing protocols, to characterize cell-type-specific enhancers that should enable genetic access and perturbation of gene function across mammalian cell types. Focusing on the highly heterogeneous mammalian cerebral cortex, we apply PESCA to find enhancers and generate viral reagents capable of accessing and manipulating a subset of somatostatin-expressing cortical interneurons with high specificity. This study demonstrates the utility of this platform for developing new cell-type-specific viral reagents, with significant implications for both basic and translational research.

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 Cell-type Specific Expression Quantitative Trait Loci Associated with Alzheimer Disease in Blood and Brain Tissue

2020 ◽  
Author(s):  
Devanshi Patel ◽  
Xiaoling Zhang ◽  
John J. Farrell ◽  
Jaeyoon Chung ◽  
Thor D. Stein ◽  
...  
Keyword(s):  
Gene Expression ◽  
Quantitative Trait ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Cell Types ◽  
Eqtl Analysis ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

ABSTRACTBecause regulation of gene expression is heritable and context-dependent, we investigated AD-related gene expression patterns in cell-types in blood and brain. Cis-expression quantitative trait locus (eQTL) mapping was performed genome-wide in blood from 5,257 Framingham Heart Study (FHS) participants and in brain donated by 475 Religious Orders Study/Memory & Aging Project (ROSMAP) participants. The association of gene expression with genotypes for all cis SNPs within 1Mb of genes was evaluated using linear regression models for unrelated subjects and linear mixed models for related subjects. Cell type-specific eQTL (ct-eQTL) models included an interaction term for expression of “proxy” genes that discriminate particular cell type. Ct-eQTL analysis identified 11,649 and 2,533 additional significant gene-SNP eQTL pairs in brain and blood, respectively, that were not detected in generic eQTL analysis. Of note, 386 unique target eGenes of significant eQTLs shared between blood and brain were enriched in apoptosis and Wnt signaling pathways. Five of these shared genes are established AD loci. The potential importance and relevance to AD of significant results in myeloid cell-types is supported by the observation that a large portion of GWS ct-eQTLs map within 1Mb of established AD loci and 58% (23/40) of the most significant eGenes in these eQTLs have previously been implicated in AD. This study identified cell-type specific expression patterns for established and potentially novel AD genes, found additional evidence for the role of myeloid cells in AD risk, and discovered potential novel blood and brain AD biomarkers that highlight the importance of cell-type specific analysis.

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