ICP0 enables and monitors the function of D cyclins in herpes simplex virus 1 infected cells

Kalamvoki, Maria; Roizman, Bernard

doi:10.1073/pnas.0906905106

Cited by 22 publications

(35 citation statements)

References 31 publications

(52 reference statements)

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“…At least 3 important functions are associated with ICP0 at this stage. Thus (i) ICP0 enhances the localization of cyclin D3 to ND10 bodies that serve as precursors of replication compartments, results in activation of cdk4, and enables efficient viral replication in resting, contact-inhibited cells (4). (ii) Acting as an ubiquitin ligase, and in conjunction with the ubiquitinconjugating enzyme UbcH5a, ICP0 degrades PML and Sp100, the major constituents of ND10 (5).…”

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confidence: 99%

During its nuclear phase the multifunctional regulatory protein ICP0 undergoes proteolytic cleavage characteristic of polyproteins

Poon

Roizman

2009

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

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ICP0 is a multifunctional herpes simplex virus protein known primarily as a promiscuous transactivator. In the course of productive infection, it is localized during the first 5-7 h in the nucleus and later in the cytoplasm. In the nucleus, its primary activities are to suppress the silencing of viral DNA by host proteins, activate cdk4 through recruitment of cyclin D3 to the sites of formation of replication compartments, and degrade several cellular proteins including PML and Sp100, key components of the ND10 nuclear bodies. ICP0 is not translocated to the cytoplasm in cells infected with mutants incapable of performing these tasks. We report the unexpected finding that ICP0 is cleaved into several discrete polypeptides by a proteasome-independent process. The products of this cleavage accumulate in cells infected with ICP0 mutants incapable of degrading PML and therefore are retained in the nucleus. In the second step, the products of the initial cleavage of wild-type virus-infected cells are themselves subject to proteasome-dependent degradation. The average half life of intact ICP0 during the nuclear phase is approximately 1 h. The proteasomeindependent cleavage products are no longer detected at late times corresponding to the cytoplasmic phase of ICP0. The results are consistent with the hypothesis that the cleavage products of ICP0 function in topologically distinct domains during its nuclear phase.herpes simplex virus ͉ nuclear proteolysis ͉ proteasome dependent

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confidence: 99%

During its nuclear phase the multifunctional regulatory protein ICP0 undergoes proteolytic cleavage characteristic of polyproteins

Poon

Roizman

2009

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

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“…As noted in the introduction, the duration of its stay in the nucleus is to some extent cell type dependent and ceases only after at least 3 of the investigated nuclear functions are executed. These function are degradation of key components and dispersal of ND10 bodies, suppression of silencing of viral DNA, and recruitment of cyclin D3 to the emerging replication compartments at ND10 structures (3,6,(13)(14)(15)20). The focus of this report is on suppression of silencing of DNA introduced into cells by transfection and or infection.…”

Section: Discussionmentioning

confidence: 99%

“…The sources, properties, and propagation of HEp-2 and Vero cells have been described elsewhere (18)(19)(20). HSV-1(F), a limited-passage isolate, is the prototype strain used in this laboratory (7).…”

Section: Cells and Virusesmentioning

confidence: 99%

“…The procedures for immunofluorescence studies have been described elsewhere (18)(19)(20). Briefly, the cells, seeded in four-well slides (Erie Scientific), were fixed in 4% paraformaldehyde at the times indicated in Results; permeabilized; blocked with phosphate-buffered saline (PBS)-TBH solution consisting of 0.1% Triton X-100 in PBS, 10% human serum, and 1% bovine serum albumin (BSA); and reacted with the ICP0 exon 2 rabbit polyclonal antibody diluted 1:2,000 in PBS-TBH (21).…”

Section: Cells and Virusesmentioning

confidence: 99%

“…Lastly, ICP0 binds and recruits cyclin D3 to ND10 structures that ultimately evolve into replication compartments (20,21). The substantive finding that led to these studies is that failure in the execution of any one of these functions leads to the retention of ICP0 in the nucleus (14,15,20,21).…”

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Role of Herpes Simplex Virus ICP0 in the Transactivation of Genes Introduced by Infection or Transfection: a Reappraisal

Kalamvoki

Roizman

2010

J Virol

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Numerous studies carried out shortly after the discovery of infected cell protein 0 (ICP0) of herpes simplex virus type 1 (HSV-1) described the function of the protein as a promiscuous transactivator of genes introduced by transfection or infection (1,4,5,9,10,12,17,24,26,27,29). The enhancement of gene expression by ICP0 was particularly puzzling, since it does not bind DNA and is not known to recruit transcriptional factors to specific promoters (11). This article is a reappraisal of its function as a transactivator. We propose that its function is that of a DNA template remodeler, that the extent to which it functions in that capacity is cell type dependent, and that in an absolute sense it is not an obligate component of the transcriptional apparatus used by the virus to transcribe its genes. The experiments we report are based briefly on the following studies.Early in infection, ICP0 is located in the nucleus. At later times, ICP0 is in the cytoplasm. During its nuclear sojourn, ICP0 performs several functions. Studies of 3 of these functions are particularly illuminating. The first involves the degradation of several components of the ND10 nuclear bodies by the ubiquitin ligase function of ICP0 in conjunction with the UbcH5a ubiquitin-conjugating enzyme, followed by the dispersal of ND10 bodies (3,13,16). The second function of ICP0, executed in tandem with the

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The ERK-1 function is required for HSV-1-mediated G1/S progression in HEP-2 cells and contributes to virus growth

Colao

Pennisi

Venuti

et al. 2017

Sci Rep

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The herpes simplex virus 1 is able to readdress different cellular pathways including cell cycle to facilitate its replication and spread. During infection, the progression of the cell cycle from G1 to S phase makes the cellular replication machinery accessible to viral DNA replication. In this work we established that HSV-1, in asynchronized HEp-2 cells, strictly controls cell cycle progression increasing S-phase population from 9 hours post infection until the end of HSV-1 replication. The G1/S phases progression depends on two important proteins, cyclin E and CDK2. We demonstrate that their phosphorylated status and then their activity during the infection is strongly correlated to viral replication events. In addition, HSV-1 is able to recruit and distribute ERK1/2 proteins in a spatio-temporal fashion, highlighting its downstream regulatory effects on cellular processes. According with this data, using chemical inhibitor U0126 and ERK dominant negative cells we found that the lack of ERK1 activity affects cyclin E protein accumulation, viral gene transcription and percentage of the cells in S phase, during the viral replication. These data suggested a complex interaction between ERK, cell cycle progression and HSV-1 replication.

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ICP0 enables and monitors the function of D cyclins in herpes simplex virus 1 infected cells

Cited by 22 publications

References 31 publications

During its nuclear phase the multifunctional regulatory protein ICP0 undergoes proteolytic cleavage characteristic of polyproteins

During its nuclear phase the multifunctional regulatory protein ICP0 undergoes proteolytic cleavage characteristic of polyproteins

Role of Herpes Simplex Virus ICP0 in the Transactivation of Genes Introduced by Infection or Transfection: a Reappraisal

The ERK-1 function is required for HSV-1-mediated G1/S progression in HEP-2 cells and contributes to virus growth

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