General and Specific Alterations in Programming of Global Viral Gene Expression during Infection by VP16 Activation-Deficient Mutants of Herpes Simplex Virus Type 1

Yang, William; Devi-Rao, G B; Ghazal, Peter; Wagner, Edward K.; Triezenberg, Steven J.

doi:10.1128/jvi.76.24.12758-12774.2002

Cited by 36 publications

(46 citation statements)

References 41 publications

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“…2A). In contrast, infection by RP5 (lacking the VP16 AD) resulted in a dramatic reduction in viral gene expression, in agreement with prior reports (53,70). To test whether this decreased expression corresponded to a failure to recruit the general transcription machinery to IE gene promoters, ChIP assays were performed using antibodies directed against the GTF TBP and RNA Pol II.…”

Section: Resultsmentioning

confidence: 68%

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VP16-Dependent Association of Chromatin-Modifying Coactivators and Underrepresentation of Histones at Immediate-Early Gene Promoters during Herpes Simplex Virus Infection

Herrera

Triezenberg

2004

J Virol

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177

253

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During infection by herpes simplex virus type 1 (HSV-1), the virion protein VP16 activates the transcription of viral immediate-early (IE) genes. Genetic and biochemical assays have shown that the potent transcriptional activation domain of VP16 can associate with general transcription factors and with chromatin-modifying coactivator proteins of several types. The latter interactions are particularly intriguing because previous reports indicate that HSV-1 DNA does not become nucleosomal during lytic infection. In the present work, chemical cross-linking and immunoprecipitation assays were used to probe the presence of activators, general transcription factors, and chromatin-modifying coactivators at IE gene promoters during infection of HeLa cells by wild-type HSV-1 and by RP5, a viral strain lacking the VP16 transcriptional activation domain. The presence of VP16 and Oct-1 at IE promoters did not depend on the activation domain. In contrast, association of RNA polymerase II, TATA-binding protein, histone acetyltransferases (p300 and CBP), and ATP-dependent remodeling proteins (BRG1 and hBRM) with IE gene promoters was observed in wild-type infections but was absent or reduced in cells infected by RP5. In contrast to the previous evidence for nonnucleosomal HSV-1 DNA, histone H3 was found associated with viral DNA at early times of infection. Interestingly, histone H3 was underrepresented on IE promoters in a manner dependent on the VP16 activation domain. Thus, the VP16 activation domain is responsible for recruiting general transcription factors and coactivators to IE promoters and also for dramatically reducing the association of histones with those promoters.The activation domain of VP16 (VP16 AD) from herpes simplex virus type I (HSV-1) has been widely used as a model for the study of transcriptional activation in eukaryotes. During infection, VP16 triggers the cascade of viral gene expression by activating transcription of the viral immediate-early (IE) genes (65). VP16 forms a DNA-binding complex with the cellular proteins Oct-1 and HCF-1 at specific cis elements present in the IE gene promoters (27,40,48,68). The potent VP16 AD (10, 55), often artificially fused to a heterologous DNA-binding domain (47), can activate transcription in a wide range of organisms, including yeasts, insects, plants, and mammals (3,47,58,66), indicating that mechanisms of transcriptional activation are broadly conserved through evolution.Interactions of the VP16 AD with general transcription factors (GTFs) including transcription factor IIB (TFIIB), TFIIH, TATA-binding protein (TBP), and TBP-associated factors (TAFs) suggest that the VP16 AD might activate transcription by stimulating the assembly of an RNA polymerase II (RNA Pol II) preinitiation complex (13,17,24,31,56,67). Consistent with this model, in vitro experiments have demonstrated the ability of the VP16 AD to promote the formation of the ternary complex formed by TFIIA, TFIID, and TATA box DNA (25). The VP16 AD might also recruit the RNA Pol II holoenzyme through i...

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Section: Resultsmentioning

confidence: 68%

“…The VP16 AD is required for efficient transcription of viral IE genes both in transfection experiments and during HSV-1 infection (53,55,62). Infection by RP5, a mutant viral (53,70). ChIP assays were adapted to detect the association of specific proteins with viral promoters during lytic infection by HSV-1.…”

Section: Resultsmentioning

confidence: 99%

VP16-Dependent Association of Chromatin-Modifying Coactivators and Underrepresentation of Histones at Immediate-Early Gene Promoters during Herpes Simplex Virus Infection

Herrera

Triezenberg

2004

J Virol

Self Cite

177

253

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“…Microarray analysis has been increasingly utilized to investigate global transcriptional alterations following viral infection of many types, including human immunodeficiency virus (20,83), herpesviruses (i.e., herpes simplex virus, varicellazoster virus, Epstein-Barr virus, cytomegalovirus, and Kaposi's sarcoma-associated herpesvirus) (10,29,36,39,90,93), rotavirus (17), Sindbis virus (38), hepatitis B (32) and C (5) viruses, FIG. 4.…”

Section: Discussionmentioning

confidence: 99%

Reovirus-Induced Alteration in Expression of Apoptosis and DNA Repair Genes with Potential Roles in Viral Pathogenesis

DeBiasi

Clarke

Meintzer

et al. 2003

J Virol

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Reoviruses are a leading model for understanding cellular mechanisms of virus-induced apoptosis. Reoviruses induce apoptosis in multiple cell lines in vitro, and apoptosis plays a key role in virus-induced tissue injury of the heart and brain in vivo. The activation of transcription factors NF-B and c-Jun are key events in reovirus-induced apoptosis, indicating that new gene expression is critical to this process. We used highdensity oligonucleotide microarrays to analyze cellular transcriptional alterations in HEK293 cells after infection with reovirus strain T3A (i.e., apoptosis inducing) compared to infection with reovirus strain T1L (i.e., minimally apoptosis inducing) and uninfected cells. These strains also differ dramatically in their potential to induce apoptotic injury in hearts of infected mice in vivo-T3A is myocarditic, whereas T1L is not. Using high-throughput microarray analysis of over 12,000 genes, we identified differential expression of a defined subset of genes involved in apoptosis and DNA repair after reovirus infection. This provides the first comparative analysis of altered gene expression after infection with viruses of differing apoptotic phenotypes and provides insight into pathogenic mechanisms of virus-induced disease.

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“…The structure of HMBA resembles that of HDAC inhibitors but the compound itself does not inhibit histone deacetylase (HDAC) activity or induce histone hyperacetylation [16]. The exact mechanism by which HMBA exerts its activity on HSV gene transcription is unknown, while its overall effects on patterns of HSV gene expression have been deemed significant [17].…”

Section: Introductionmentioning

confidence: 99%

Hexamethylene bisacetamide leads to reduced helper virus‐free HSV‐1 amplicon expression titers via suppression of ICP0

Burris

Silva

Narrow

et al. 2007

The Journal of Gene Medicine

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The Herpes simplex virus (HSV)-derived amplicon vector has evolved into a promising gene transfer platform for widespread DNA delivery in gene replacement strategies and vaccine development given its ease of molecular manipulation, large transgene capacity, and transduction efficiencies of numerous cell types in vivo. The recent development of helper virus-free packaging methodologies bodes well for this vector system in its eventual implementation as a clinically viable therapeutic modality. For realization of clinical application, efforts have been made to enhance yields and quality of helper-free amplicon stocks. Hexamethylene bisacetamide (HMBA), a hybrid polar compound that exhibits stimulatory activity of HSV-1 immediate-early gene expression, has been employed as a standard reagent in helper virus-free packaging given its purported mode of action on virus gene expression kinetics. Unexpectedly, we have found that HMBA exhibits no titer-enhancing activity; in contrast, the compound enhances the proportion of amplicon virions that are non-expressive. Omission of HMBA during vector packaging led to a marked reduction in the ratios of vector genometransducing to transgene-expressing virions. This effect was neither packaging cell-specific nor amplicon promoter-dependent. Analysis of resultant vector stocks indicated amplicon genome replication/concatenation was unaffected, but the level of particle-associated ICP0 was reduced in stocks packaged in the presence of HMBA. Inclusion of a co-transfected, ICP0-expressing plasmid into the packaging process led to significant rescue of amplicon expression titers, indicating that regulation of ICP0 concentrations is critical for maintenance of the amplicon genome expressive state.

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General and Specific Alterations in Programming of Global Viral Gene Expression during Infection by VP16 Activation-Deficient Mutants of Herpes Simplex Virus Type 1

Cited by 36 publications

References 41 publications

VP16-Dependent Association of Chromatin-Modifying Coactivators and Underrepresentation of Histones at Immediate-Early Gene Promoters during Herpes Simplex Virus Infection

VP16-Dependent Association of Chromatin-Modifying Coactivators and Underrepresentation of Histones at Immediate-Early Gene Promoters during Herpes Simplex Virus Infection

Reovirus-Induced Alteration in Expression of Apoptosis and DNA Repair Genes with Potential Roles in Viral Pathogenesis

Hexamethylene bisacetamide leads to reduced helper virus‐free HSV‐1 amplicon expression titers via suppression of ICP0

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