Transcriptional Control of the Equine Herpesvirus 1 Immediate Early Gene

Lewis, Jill B.; Thompson, Yeini G.; Caughman, Gretchen B.

doi:10.1006/viro.1993.1658

Cited by 28 publications

(24 citation statements)

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“…IE gene transcription occurs in the absence of viral protein synthesis and is induced by E-TIF (7,28,29,37). The IE protein activates expression of the early promoters, autoregulates expression of its own promoter (40), and is essential for EHV-1 replication, since deletion of both copies of the IE gene renders the virus unable to grow on noncomplementing cells (16).…”

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confidence: 99%

Characterization of the trans -Activation Properties of Equine Herpesvirus 1 EICP0 Protein

Bowles

Kim

O’Callaghan

2000

J Virol

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The EICP0 protein of equine herpesvirus 1 (EHV-1) is an early, viral regulatory protein that independently trans-activates EHV-1 immediate-early (IE), early, ␥1 late, and ␥2 late promoters. To assess whether this powerful trans-activator functions in conjunction with three other EHV-1 regulatory proteins to activate expression of the various classes of viral promoters, transient cotransfection assays were performed in which effector plasmids expressing the EICP22, EICP27, and IE proteins were used either singly or in combination with an EICP0 effector construct. These analyses revealed that (i) independently, the EICP0 and IE proteins are powerful trans-activators but do not function synergistically, (ii) the IE protein inhibits the ability of the EICP0 protein to trans-activate the IE, ␥1 late, and ␥2 late promoters, (iii) the EICP22 and EICP0 proteins do not function together to significantly trans-activate any EHV-1 promoter, and (iv) the EICP27 and EICP0 proteins function synergistically to trans-activate the early and ␥1 late promoters. A panel of EICP0 truncation and deletion mutant plasmids was generated and used in experiments to define the domains of the 419-aminoacid (aa) EICP0 protein that are important for the trans-activation of each class of EHV-1 promoters. These studies revealed that (i) carboxy-terminal truncation mutants of the EICP0 protein exhibited a progressive loss of trans-activating ability as increasing portions of the carboxy terminus were removed, (ii) the amino terminus of the EICP0 protein containing the RING finger (aa 8 to 46) and the acidic region (aa 71 to 84) was necessary but not sufficient for activation of all classes of EHV-1 promoters, (iii) the RING finger was absolutely essential for activation of EHV-1 promoters, since deletion of the entire RING finger motif (aa 8 to 46) or a portion of it (aa 19 to 30) completely abrogated the ability of these mutants to activate any promoter tested, (iv) the acidic region contributed to the ability of the EICP0 protein to activate the early and ␥1 late promoters, and deletion of the acidic region enhanced the ability of this mutant to activate the IE promoter, (v) the carboxy terminus (aa 325 to 419), which is rich in glutamine residues, was dispensable for the EICP0 trans-activation function, (vi) a motif resembling a nuclear localization signal (aa 289 to 293) was unnecessary for the EICP0 protein to trans-activate promoters of any temporal class, and (vii) the EICP0 protein was phosphorylated during infection, and deletion of the serine-rich region (aa 210 to 217), a potential site for phosphorylation, reduced by more than 70% the ability of the EICP0 protein to activate the ␥2 late class of promoters.

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Characterization of the trans -Activation Properties of Equine Herpesvirus 1 EICP0 Protein

Bowles

Kim

O’Callaghan

2000

J Virol

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“…Homologs of VP16 have now been identified in other herpesviruses, including varicella-zoster virus (7,27), equine herpesviruses (EHV) 1 and 4 (23,38,39), and bovine herpesvirus 1 (BHV-1) (3). The primary structural attributes of VP16, demonstrated to be important for interaction with Oct-1 and HCF, are retained in these homologs.…”

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Conformational Alteration of Oct-1 upon DNA Binding Dictates Selectivity in Differential Interactions with Related Transcriptional Coactivators

Misra

Walter

Yang

et al. 1996

Molecular and Cellular Biology

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VP16 (termed VP16-H here) of herpes simplex virus (HSV) belongs to a family of related regulatory proteins which includes VP16-B of bovine herpesvirus (BHV).We show that VP16-B, while also being a powerful transactivator of transcription dependent on Oct-1 binding sites in its target promoters, has virtually no activity on a defined VP16-H-responsive, octamer-containing target promoter. While Oct-1 binds equally well to the VP16-B-responsive and -nonresponsive sites, VP16-B interacts with Oct-1 only when Oct-1 is bound to the BHV octamer site and not when it is bound to the HSV site. We show from the analysis of chimeric proteins that the ability of VP16-B to discriminate between the Oct-1 forms depends on features of its N-terminal region. We also show from an analysis of chimeric DNA motifs that sequences that lie 3 to the POU domain-contacting region of the HSV octamer site play a role in making it unresponsive to VP16-B. Finally, we show by high-resolution hydroxyl radical footprint analysis that the conformation of Oct-1 is different on the two sites. These results augment our previous report on an allosteric effect of DNA signals on the conformation of bound proteins and indicate that different conformations of the same DNA binding protein can be recognized selectively by related members of interacting regulatory proteins. The possible implications of our observations for selective gene regulation by Oct-1, a ubiquitous transcription factor, and other multimember transcription families are discussed.A fundamental aspect of the proper orchestration of coordinate and differential gene expression is the assembly of multicomponent transcription complexes involving different combinations and spatial arrangements of transcription factors. Given the multiplicity of potential interactions between regulatory proteins and the identification of numerous large families of DNA binding proteins with related if not identical binding sites, an understanding of precisely how the appropriate combinations are selected and assembled is crucial to the elucidation of the basis of gene control.

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“…The sole IE gene of EHV-1, a homologue of the herpes simplex virus type 1 (HSV-1) ICP4 gene, is transcribed independently of de novo protein synthesis from gene 62 and is absolutely essential for virus replication (18). The EHV-1 IE protein is a multifunctional, regulatory protein capable of modulating early and late promoters independently of or synergistically with early regulatory proteins (4,25,27,55,56,67).IE gene transcription becomes augmented and strongly stimulated by the virion-associated transcriptional regulator of EHV-1 gene expression, variably referred to as ETIF or VP16-E, expressed from the true late (␥2) EHV-1 gene 12 (33,34,44,44,45,45). ETIF is the EHV-1 homologue of HSV-1 VP16 also known as ␣-trans-inducing factor (␣-TIF) (5).…”

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confidence: 99%

“…IE gene transcription becomes augmented and strongly stimulated by the virion-associated transcriptional regulator of EHV-1 gene expression, variably referred to as ETIF or VP16-E, expressed from the true late (␥2) EHV-1 gene 12 (33,34,44,44,45,45). ETIF is the EHV-1 homologue of HSV-1 VP16 also known as ␣-trans-inducing factor (␣-TIF) (5).…”

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The α-TIF (VP16) Homologue (ETIF) of Equine Herpesvirus 1 Is Essential for Secondary Envelopment and Virus Egress

Einem

Schumacher

O’Callaghan

et al. 2006

J Virol

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The equine herpesvirus 1 (EHV-1) ␣-trans-inducing factor homologue (ETIF; VP16-E) is a 60-kDa virion component encoded by gene 12 (ORF12) that transactivates the immediate-early gene promoter. Here we report on the function of EHV-1 ETIF in the context of viral infection. An ETIF-null mutant from EHV-1 strain RacL11 (vL11⌬ETIF) was constructed and analyzed. After transfection of vL11⌬ETIF DNA into RK13 cells, no infectious virus could be reconstituted, and only single infected cells or small foci containing up to eight infected cells were detected. In contrast, after transfection of vL11⌬ETIF DNA into a complementing cell line, infectious virus could be recovered, indicating the requirement of ETIF for productive virus infection. The growth defect of vL11⌬ETIF could largely be restored by propagation on the complementing cell line, and growth on the complementing cell line resulted in incorporation of ETIF in mature and secreted virions. Lowand high-multiplicity infections of RK13 cells with phenotypically complemented vL11⌬ETIF virus resulted in titers of virus progeny similar to those used for infection, suggesting that input ETIF from infection was recycled. Ultrastructural studies of vL11⌬ETIF-infected cells demonstrated a marked defect in secondary envelopment at cytoplasmic membranes, resulting in very few enveloped virions in transport vesicles or extracellular space. Taken together, our results demonstrate that ETIF has an essential function in the replication cycle of EHV-1, and its main role appears to be in secondary envelopment.Equine herpesvirus type 1 (EHV-1) is classified as a member of the Varicellovirus genus within the Alphaherpesvirinae subfamily. In analogy to the situation seen in other alphaherpesviruses, expression of EHV-1 genes is regulated in a cascadelike fashion. An immediate-early (IE), early, and late phase of gene expression are recognized, depending on the order of the appearance of transcripts and proteins during lytic infection (6,21,21,26). From the approximately 76 EHV-1 genes, a single immediate-early (ie-and ␣-) gene, 49 early (e-and ␤-) genes, and 26 late (l-, ␥1-, and ␥2-) genes have been identified (21,24,24,57,57,67,67). The sole IE gene of EHV-1, a homologue of the herpes simplex virus type 1 (HSV-1) ICP4 gene, is transcribed independently of de novo protein synthesis from gene 62 and is absolutely essential for virus replication (18). The EHV-1 IE protein is a multifunctional, regulatory protein capable of modulating early and late promoters independently of or synergistically with early regulatory proteins (4,25,27,55,56,67).IE gene transcription becomes augmented and strongly stimulated by the virion-associated transcriptional regulator of EHV-1 gene expression, variably referred to as ETIF or VP16-E, expressed from the true late (␥2) EHV-1 gene 12 (33,34,44,44,45,45). ETIF is the EHV-1 homologue of HSV-1 VP16 also known as ␣-trans-inducing factor (␣-TIF) (5). Homologues of HSV-1 ␣-TIF have been identified in several other alphaherpesviruses, including varicella-zost...

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Transcriptional Control of the Equine Herpesvirus 1 Immediate Early Gene

Cited by 28 publications

References 0 publications

Characterization of the trans -Activation Properties of Equine Herpesvirus 1 EICP0 Protein

Characterization of the trans -Activation Properties of Equine Herpesvirus 1 EICP0 Protein

Conformational Alteration of Oct-1 upon DNA Binding Dictates Selectivity in Differential Interactions with Related Transcriptional Coactivators

The α-TIF (VP16) Homologue (ETIF) of Equine Herpesvirus 1 Is Essential for Secondary Envelopment and Virus Egress

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