Herpes simplex virus type 1 immediate early gene expression is stimulated by inhibition of protein synthesis.

Preston, Chris M.; Rinaldi, A.; Nicholl, Mary Jane

doi:10.1099/0022-1317-79-1-117

Cited by 40 publications

(50 citation statements)

References 47 publications

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“…Oligonucleotide microarrays were used to assess the changes in abundance of viral transcripts in HeLa cells infected for 2, 4, and 8 h with RP5/16-8. The hybridization data reported in Table 6 were compared with the results for a wt (RP5R) infection (Table 1) for each gene at each time point, and correlation coefficients were calculated for the major kinetic classes ( (22). We tested the effects of cycloheximide on the global pattern of viral gene expression in the absence or presence of stimulation by the VP16 activation domain.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, protein synthesis inhibitors such as cycloheximide can increase the expression of viral IE genes (6,22) by a means likely to involve cellular stress responses that influence either RNA synthesis or RNA stability. During RP5 infection at low multiplicity, cycloheximide enhanced the transcription of only two IE genes, those encoding ICP0 and ICP4.…”

Section: Vol 76 2002 Microarray Analysis Of Hsv-1 Vp16 Activation Mmentioning

confidence: 99%

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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

Yang

Devi-Rao

Ghazal³

et al. 2002

J Virol

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During productive infection by herpes simplex virus 1 (HSV-1), viral gene expression occurs in a temporally regulated cascade in which transcription of the viral immediate-early (IE) genes is strongly stimulated by the virion protein VP16. We have employed an oligonucleotide microarray to examine the effect of VP16 mutations on the overall pattern of viral gene expression following infection of HeLa cells. This microarray detects essentially all HSV-1 transcripts with relative and absolute levels correlating well with known kinetics of expression. This analysis revealed that deletion of the VP16 activation domain sharply reduced overall viral gene expression; moreover, the pattern of this reduced expression varied greatly from the pattern of a wild-type (wt) infection. However, when this mutant virus was delivered at a high multiplicity of infection or in the presence of the cellular stress inducer hexamethylene bisacetamide, expression was largely restored to the wt levels and pattern. Infection with virions that deliver wt VP16 protein at the start of infection but synthesize only truncated VP16 resulted in a normal kinetic cascade. This suggests that newly synthesized VP16 does not play a significant role in the expression of later classes of transcripts. The VP16 activation domain comprises two subregions. Deletion of the C-terminal subregion resulted in minimal changes in the level and profile of gene expression compared to a normal (wt) cascade. In contrast, deletion of the N-terminal subregion reduced the overall expression levels and skewed the relative levels of IE transcripts but did not significantly alter the kinetic pattern of early and late transcript expression. We conclude that the general activation of IE gene transcription by VP16, but not the specific ratios of IE transcripts, is necessary for the subsequent ordered expression of viral genes. Moreover, this report establishes the feasibility of microarray analysis for globally assessing viral gene expression programs as a function of the conditions of infection.During productive infection of mammalian cells by herpes simplex virus type 1 (HSV-1), transcription of the viral genes occurs in a coordinated cascade (11, 28; reviewed in references 34 and 37). The five viral immediate-early (IE) genes are transcribed rapidly upon viral entry and uncoating. Synthesis of the IE proteins peaks at approximately 2 to 4 h postinfection (hpi), but they continue to accumulate throughout the infection. The IE proteins stimulate the expression of the early (E) and late (L) genes and also have autoregulatory functions.The virion protein VP16 activates transcription of the IE genes through specific sequence elements in the IE promoters (reviewed in reference 19). VP16 interacts with the viral DNA template by associating with the cellular proteins Oct-1 and HCF-1 at promoter elements containing the sequence TAAT-GARAT (where R represents purine) (reviewed in reference 9). Activation by VP16 is also exerted through DNA sequences bound by the cellular protein GABP ...

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Section: Resultsmentioning

confidence: 99%

Section: Vol 76 2002 Microarray Analysis Of Hsv-1 Vp16 Activation Mmentioning

confidence: 99%

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

Devi-Rao

Ghazal³

et al. 2002

J Virol

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“…In one approach to achieve this goal, ICP0 has been substituted with similar IE genes from other herpesviruses, including the pp71 gene of human cytomegalovirus (HCMV) (33,34), a betaherpesvirus, with the notion that the products of these genes may provide the antisilencing functions of ICP0 without toxicity (35). However, it is well-known that pp71 degrades a chromatin-remodeling factor, hDaxx, followed by disruption of the hDaxx-ATRX complex (36,37) and members of the retinoblastoma tumor-suppressor family of proteins (38).…”

Section: Discussionmentioning

confidence: 99%

Herpes simplex viral-vector design for efficient transduction of nonneuronal cells without cytotoxicity

Miyagawa

Marino

Verlengia

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

109

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The design of highly defective herpes simplex virus (HSV) vectors for transgene expression in nonneuronal cells in the absence of toxic viral-gene activity has been elusive. Here, we report that elements of the latency locus protect a nonviral promoter against silencing in primary human cells in the absence of any viral-gene expression. We identified a CTCF motif cluster 5′ to the latency promoter and a known long-term regulatory region as important elements for vigorous transgene expression from a vector that is functionally deleted for all five immediate-early genes and the 15-kb internal repeat region. We inserted a 16.5-kb expression cassette for full-length mouse dystrophin and report robust and durable expression in dystrophin-deficient muscle cells in vitro. Given the broad cell tropism of HSV, our design provides a nontoxic vector that can accommodate large transgene constructs for transduction of a wide variety of cells without vector integration, thereby filling an important void in the current arsenal of gene-therapy vectors.

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“…15,18 CHX addition during HSV infection has been reported to stimulate the expression of viral IE genes. 35 We included STS treatment in this study as an additional positive control for the induction of apoptosis. 15 We performed immunoblots for the PARP and caspase-3 death factors, as well as for the p53 protein following the infections and treatments (Figure 5a).…”

Section: Adenoviral Dna-containing Human Kidney 293 Cells Are Resistamentioning

confidence: 99%

Viral oncoapoptosis of human tumor cells

Aubert

Blaho

2003

Gene Ther

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Many cancer cells refractory to radiation treatment and chemotherapy proliferate because of loss of intrinsic programmed cell death (apoptosis) regulation. Consequently, the resolution of these cancers are many times outside the management capabilities of conventional therapeutics. We now report that replication-defective D27 herpes simplex virus (rd D27) triggers apoptosis in three representative transformed human cell lines. Susceptibility to virus-induced cell death is dependent on the abundance and distribution of modified p53 protein in the tumor cells indicating specific targeting of the treatment. Primary human and mouse fibroblast cells that produce modified p53 are resistant to rd D27 killing but not to apoptosis induced by nonviral environmental factors. These results suggest that induction of apoptosis by nonreplicating virus is a feasible genetic therapy approach for killing human cancer cells. Our findings may have important implications in designing novel virus-based anticancer strategies in appropriate animal model systems.

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Herpes simplex virus type 1 immediate early gene expression is stimulated by inhibition of protein synthesis.

Cited by 40 publications

References 47 publications

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

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

Herpes simplex viral-vector design for efficient transduction of nonneuronal cells without cytotoxicity

Viral oncoapoptosis of human tumor cells

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