scholarly journals Herpes simplex virus 1 alpha regulatory protein ICP0 interacts with and stabilizes the cell cycle regulator cyclin D3.

1997 ◽  
Vol 71 (10) ◽  
pp. 7328-7336 ◽  
Author(s):  
Y Kawaguchi ◽  
C Van Sant ◽  
B Roizman
Keyword(s):  
Cell Cycle ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Regulatory Protein ◽  
Cyclin D3 ◽  
Herpes Simplex Virus 1 ◽  
Cell Cycle Regulator ◽  
Protein Icp0 ◽  
Simplex Virus ◽  
Cell Cycle Regulator Cyclin

scholarly journals E2F Proteins Are Posttranslationally Modified Concomitantly with a Reduction in Nuclear Binding Activity in Cells Infected with Herpes Simplex Virus 1

2000 ◽  
Vol 74 (17) ◽  
pp. 7842-7850 ◽  
Author(s):  
Sunil J. Advani ◽  
Ralph R. Weichselbaum ◽  
Bernard Roizman
Keyword(s):  
Cell Cycle ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Human Lung ◽  
S Phase ◽  
Cyclin D3 ◽  
Lung Fibroblasts ◽  
Herpes Simplex Virus 1 ◽  
Human Lung Fibroblasts ◽  
Simplex Virus

ABSTRACT The transition from G1 to S phase in the cell cycle requires sequential activation of cyclin-dependent kinase 4 (cdk4) and cdk2, which phosphorylate the retinoblastoma protein, causing the release of E2F. Free E2F upregulates the transcription of genes involved in S phase and cell cycle progression. Recent studies from this and other laboratories have shown that herpes simplex virus 1 stabilizes cyclin D3 early in infection and that early events in viral replication are sensitive to inhibitors of some cdks. On the other hand cdk2 is not activated. Here we report studies on the status of members of E2F family in cycling HEp-2 and HeLa cells and quiescent serum-starved, contact-inhibited human lung fibroblasts. The results show that (i) at 8 h postinfection or thereafter, E2F-1 and E2F-5 were posttranslationally modified and/or translocated from nucleus to the cytoplasm, (ii) E2F-4 was hyperphophorylated, and (iii) overall, E2F binding to cognate DNA sites was decreased at late times after infection. These results concurrent with those cited above indicate that late in infection activation of S-phase genes is blocked both by posttranslational modification and translocation of members of E2F family to inactive compartments and by the absence of active cdk2. The observation that E2F were also posttranslationally modified in quiescent human lung fibroblasts that were not in S phase at the time of infection suggests that specific viral gene products are responsible for modification of the members of E2F family and raises the possibility that in infected cells, activation of the S phase gene is an early event in viral infection and is then shut off at late times. This is consistent with the timing of stabilization of cyclin D3 and the events blocked by inhibitors of cdks.

scholarly journals Herpes Simplex Virus 1 Regulatory Protein ICP22 Interacts with a New Cell Cycle-Regulated Factor and Accumulates in a Cell Cycle-Dependent Fashion in Infected Cells

1998 ◽  
Vol 72 (11) ◽  
pp. 8525-8531 ◽  
Author(s):  
Renato Bruni ◽  
Bernard Roizman
Keyword(s):  
Cell Cycle ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Regulatory Protein ◽  
S Phase ◽  
Cell Protein ◽  
Herpes Simplex Virus 1 ◽  
Infected Cells ◽  
Cycle Dependent ◽  
Simplex Virus

ABSTRACT The herpes simplex virus 1 infected cell protein 22 (ICP22), the product of the α22 gene, is a nucleotidylylated and phosphorylated nuclear protein with properties of a transcriptional factor required for the expression of a subset of viral genes. Here, we report the following. (i) ICP22 interacts with a previously unknown cellular factor designated p78 in the yeast two-hybrid system. The p78 cDNA encodes a polypeptide with a distribution of leucines reminiscent of a leucine zipper. (ii) In uninfected and infected cells, antibody to p78 reacts with two major bands with an apparentM r of 78,000 and two minor bands with apparentM rs of 62,000 and 55,000. (ii) p78 also interacts with ICP22 in vitro. (iii) In uninfected cells, p78 was dispersed largely in the nucleoplasm in HeLa cells and in the nucleoplasm and cytoplasm in HEp-2 cells. After infection, p78 formed large dense bodies which did not colocalize with the viral regulatory protein ICP0. (iv) Accumulation of p78 was cell cycle dependent, being highest very early in S phase. (v) The accumulation of ICP22 in synchronized cells was highest in early S phase, in contrast to the accumulation of another protein, ICP27, which was relatively independent of the cell cycle. (vi) In the course of the cell cycle, ICP22 was transiently modified in an aberrant fashion, and this modification coincided with expression of p78. The results suggest that ICP22 interacts with and may be stabilized by cell cycle-dependent proteins.

scholarly journals Depletion of CoREST Does Not Improve the Replication of ICP0 Null Mutant Herpes Simplex Virus Type 1

2010 ◽  
Vol 84 (7) ◽  
pp. 3695-3698 ◽  
Author(s):  
Roger D. Everett
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Regulatory Protein ◽  
Null Mutant ◽  
Protein Icp0 ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT It has been proposed that the cellular corepressor protein CoREST is involved in repressing herpes simplex virus type 1 (HSV-1) infection in the absence of the viral regulatory protein ICP0. This proposal predicts that depletion of CoREST should improve the plaque-forming efficiency and replication of ICP0 null mutant virus. To test this hypothesis, human HepaRG cells that were highly depleted of CoREST were isolated using RNA interference technology. Depletion of CoREST had no effect on the replication of ICP0 null mutant HSV-1, demonstrating that CoREST does not play an influential role in regulating HSV-1 infection in this cell type.

scholarly journals The Interaction of Herpes Simplex Virus 1 Regulatory Protein ICP22 with the cdc25C Phosphatase Is Enabled In Vitro by Viral Protein Kinases US3 and UL13

2008 ◽  
Vol 82 (9) ◽  
pp. 4533-4543 ◽  
Author(s):  
Benjamin A. Smith-Donald ◽  
Bernard Roizman
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Protein Kinase ◽  
Regulatory Protein ◽  
Wild Type Mouse ◽  
Cyclin B1 ◽  
Herpes Simplex Virus 1 ◽  
Infected Cells ◽  
Simplex Virus

ABSTRACT Earlier studies have shown that ICP22 and the UL13 protein kinase but not the US3 kinase are required for optimal expression of a subset of late (γ2) genes exemplified by UL38, UL41, and US11. In primate cells, ICP22 mediates the disappearance of inactive isoforms of cdc2 and degradation of cyclins A and B1. Active cdc2 acquires a new partner, the viral DNA synthesis processivity factor UL42. The cdc2-UL42 complex recruits and phosphorylates topoisomerase IIα for efficient expression of the γ2 genes listed above. In uninfected cells, the cdc25C phosphatase activates cdc2 by removing two inhibitory phosphates. The accompanying report shows that in the absence of cdc25C, the rate of degradation of cyclin B1 is similar to that occurring in infected wild-type mouse embryo fibroblast cells but the levels of cdc2 increase, and the accumulation of a subset of late proteins and virus yields are reduced. This report links ICP22 with cdc25C. We show that in infected cells, ICP22 and US3 protein kinase mediate the phosphorylation of cdc25C at its C-terminal domain. In in vitro assays with purified components, both UL13 and US3 viral kinases phosphorylate cdc25C and ICP22. cdc25C also interacts with cdc2. However, in infected cells, the ability of cdc25C to activate cdc2 by dephosphorylation of the inactive cdc2 protein is reduced. Coupled with the phosphorylation of cdc25C by the US3 kinase, the results raise the possibility that herpes simplex virus 1 diverts cdc25C to perform functions other than those performed in uninfected cells.

scholarly journals Analysis of the Functions of Herpes Simplex Virus Type 1 Regulatory Protein ICP0 That Are Critical for Lytic Infection and Derepression of Quiescent Viral Genomes

2009 ◽  
Vol 83 (10) ◽  
pp. 4963-4977 ◽  
Author(s):  
Roger D. Everett ◽  
Marie-Laure Parsy ◽  
Anne Orr
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Regulatory Protein ◽  
Lytic Infection ◽  
Viral Genomes ◽  
Protein Icp0 ◽  
Simplex Virus ◽  
Mutant Forms ◽  
Hsv 1

ABSTRACT Herpes simplex virus type 1 (HSV-1) immediate-early regulatory protein ICP0 is important for stimulating the initiation of the lytic cycle and efficient reactivation of latent or quiescent infection. Extensive investigation has suggested several potential functions for ICP0, including interference in the interferon response, disruption of functions connected with PML nuclear bodies (ND10), and inhibition of cellular histone deacetylase (HDAC) activity through an interaction with the HDAC-1 binding partner CoREST. Analysis of the significance of these potential functions and whether they are direct or indirect effects of ICP0 is complicated because HSV-1 mutants expressing mutant forms of ICP0 infect cells with widely differing efficiencies. On the other hand, transfection approaches for ICP0 expression do not allow studies of whole cell populations because of their limited efficiency. To overcome these problems, we have established a cell line in which ICP0 expression can be induced at levels pertaining during the early stages of HSV-1 infection in virtually all cells in the culture. Such cells enable 100% complementation of ICP0-null mutant HSV-1. Using cells expressing the wild type and a variety of mutant forms of ICP0, we have used this system to analyze the role of defined domains of the protein in stimulating lytic infection and derepression from quiescence. Activity in these core functions correlated well the ability of ICP0 to disrupt ND10 and inhibit the recruitment of ND10 proteins to sites closely associated with viral genomes at the onset of infection, whereas the CoREST binding region was neither sufficient nor necessary for ICP0 function in lytic and reactivating infections.

Sign in / Sign up

Export Citation Format

Share Document