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 UL12.5 Gene Product of Herpes Simplex Virus Type 1 Exhibits Nuclease and Strand Exchange Activities but Does Not Localize to the Nucleus

2004 ◽  
Vol 78 (9) ◽  
pp. 4599-4608 ◽  
Author(s):  
Nina Bacher Reuven ◽  
Susumu Antoku ◽  
Sandra K. Weller
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Intracellular Localization ◽  
Strand Exchange ◽  
Null Mutant ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT The herpes simplex virus type 1 (HSV-1) alkaline nuclease, encoded by the UL12 gene, plays an important role in HSV-1 replication, as a null mutant of UL12 displays a severe growth defect. Although the precise in vivo role of UL12 has not yet been determined, several in vitro activities have been identified for the protein, including endo- and exonuclease activities, interaction with the HSV-1 single-stranded DNA binding protein ICP8, and an ability to promote strand exchange in conjunction with ICP8. In this study, we examined a naturally occurring N-terminally truncated version of UL12 called UL12.5. Previous studies showing that UL12.5 exhibits nuclease activity but is unable to complement a UL12 null virus posed a dilemma and suggested that UL12.5 may lack a critical activity possessed by the full-length protein, UL12. We constructed a recombinant baculovirus capable of expressing UL12.5 and purified soluble UL12.5 from infected insect cells. The purified UL12.5 exhibited both endo- and exonuclease activities but was less active than UL12. Like UL12, UL12.5 could mediate strand exchange with ICP8 and could also be coimmunoprecipitated with ICP8. The primary difference between the two proteins was in their intracellular localization, with UL12 localizing to the nucleus and UL12.5 remaining in the cytoplasm. We mapped a nuclear localization signal to the N terminus of UL12, the domain absent from UL12.5. In addition, when UL12.5 was overexpressed so that some of the enzyme leaked into the nucleus, it was able to partially complement the UL12 null mutant.

scholarly journals Replication of ICP0-Null Mutant Herpes Simplex Virus Type 1 Is Restricted by both PML and Sp100

2007 ◽  
Vol 82 (6) ◽  
pp. 2661-2672 ◽  
Author(s):  
Roger D. Everett ◽  
Carlos Parada ◽  
Philippe Gripon ◽  
Hüseyin Sirma ◽  
Anne Orr
Keyword(s):  
Gene Expression ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Human Fibroblasts ◽  
Null Mutant ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Herpes simplex virus type 1 (HSV-1) mutants that fail to express the viral immediate-early protein ICP0 have a pronounced defect in viral gene expression and plaque formation in limited-passage human fibroblasts. ICP0 is a RING finger E3 ubiquitin ligase that induces the degradation of several cellular proteins. PML, the organizer of cellular nuclear substructures known as PML nuclear bodies or ND10, is one of the most notable proteins that is targeted by ICP0. Depletion of PML from human fibroblasts increases ICP0-null mutant HSV-1 gene expression, but not to wild-type levels. In this study, we report that depletion of Sp100, another major ND10 protein, results in a similar increase in ICP0-null mutant gene expression and that simultaneous depletion of both proteins complements the mutant virus to a greater degree. Although chromatin assembly and modification undoubtedly play major roles in the regulation of HSV-1 infection, we found that inhibition of histone deacetylase activity with trichostatin A was unable to complement the defect of ICP0-null mutant HSV-1 in either normal or PML-depleted human fibroblasts. These data lend further weight to the hypothesis that ND10 play an important role in the regulation of HSV-1 gene expression.

scholarly journals Herpes Simplex Virus Type 1 Regulatory Protein ICP0 Does Not Protect Cyclins D1 and D3 from Degradation during Infection

2004 ◽  
Vol 78 (18) ◽  
pp. 9599-9604 ◽  
Author(s):  
Roger D. Everett
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Viral Infection ◽  
Herpes Simplex Virus Type ◽  
Regulatory Protein ◽  
Cell Type ◽  
Protein Icp0 ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Previous reports have suggested that herpes simplex virus type 1 (HSV-1) immediate-early regulatory protein ICP0 stabilizes cyclins D1 and D3 during infection by inducing the degradation of cdc34, the E2-conjugating enzyme that is responsible for regulating the stability of these cyclins. Since ICP0 has complex effects on the progress of viral infection that vary greatly with cell type and viral dose, it can be difficult to distinguish between direct effects caused by ICP0 itself and indirect effects caused by the rate of the progression of infection in the absence of ICP0 at the chosen multiplicity of infection. This report describes the fates of cdc34 and cyclins D1 and D3 during HSV-1 infection under conditions that ensured that viral infection and gene expression were proceeding at equivalent rates in the presence and absence of ICP0. It was confirmed that both D-type cyclins were unstable during HSV-1 infection of a variety of cell types, but no effect on cdc34 was observed, even when high levels of ICP0 were expressed. Furthermore, there was no evidence that ICP0 protected either cyclin D1 or cyclin D3 from degradation. Reconstruction of the conditions of the experiments in the previous studies, using the stated cell type and multiplicities of infection, indicated that the original results could be explained by differences in the rate of progression of infection rather than by the presence or absence of ICP0. The data presented in this report are incompatible with the hypothesis that ICP0 induces the degradation of cdc34 and thereby stabilizes cyclins D1 and D3 during HSV-1 infection.

scholarly journals Herpes Simplex Virus Type 1 Regulatory Protein ICP0 Aids Infection in Cells with a Preinduced Interferon Response but Does Not Impede Interferon-Induced Gene Induction

2009 ◽  
Vol 83 (10) ◽  
pp. 4978-4983 ◽  
Author(s):  
Roger D. Everett ◽  
Anne Orr
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Herpes Simplex Virus Type ◽  
Cultured Cells ◽  
Regulatory Protein ◽  
Multiplicity Of Infection ◽  
Protein Icp0 ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Several independent lines of evidence indicate that interferon-mediated innate responses are involved in controlling herpes simplex virus type 1 (HSV-1) infection and that the viral immediate-early regulatory protein ICP0 augments HSV-1 replication in interferon-treated cells. However, this is a complex situation in which the experimental outcome is determined by the choice of multiplicity of infection and cell type and by whether cultured cells or animal models are used. It is now known that neither STAT1 nor interferon regulatory factor 3 (IRF-3) play essential roles in the replication defect of ICP0-null mutant HSV-1 in cultured cells. This study set out to investigate the specific role of ICP0 in HSV-1 resistance to the interferon defense. We have used a cell line in which ICP0 expression can be induced at levels similar to those during the early stages of a normal infection to determine whether ICP0 by itself can interfere with interferon or IRF-3-dependent signaling and whether ICP0 enables the virus to circumvent the effects of interferon-stimulated genes (ISGs). We found that the presence of ICP0 was unable to compromise ISG induction by either interferon or double-stranded RNA. On the other hand, ICP0 preexpression reduced but did not eliminate the inhibitory effects of ISGs on HSV-1 infection, with the extent of the relief being highly dependent on multiplicity of infection. The results are discussed in terms of the relationships between ICP0 and intrinsic and innate antiviral resistance mechanisms.

scholarly journals A Gene Capable of Blocking Apoptosis Can Substitute for the Herpes Simplex Virus Type 1 Latency-Associated Transcript Gene and Restore Wild-Type Reactivation Levels

2002 ◽  
Vol 76 (3) ◽  
pp. 1224-1235 ◽  
Author(s):  
Guey-Chuen Perng ◽  
Barak Maguen ◽  
Ling Jin ◽  
Kevin R. Mott ◽  
Nelson Osorio ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Gene Function ◽  
Herpes Simplex Virus Type ◽  
Null Mutant ◽  
Wild Type ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT After ocular herpes simplex virus type 1 (HSV-1) infection, the virus travels up axons and establishes a lifelong latent infection in neurons of the trigeminal ganglia. LAT (latency-associated transcript), the only known viral gene abundantly transcribed during HSV-1 neuronal latency, is required for high levels of reactivation. The LAT function responsible for this reactivation phenotype is not known. Recently, we showed that LAT can block programmed cell death (apoptosis) in neurons of the trigeminal ganglion in vivo and in tissue culture cells in vitro (G.-C. Perng et al., Science 287:1500–1503, 2000; M. Inman et al., J. Virol. 75:3636–3646, 2001). Consequently, we proposed that this antiapoptosis function may be a key to the mechanism by which LAT enhances reactivation. To study this further, we constructed a recombinant HSV-1 virus in which the HSV-1 LAT gene was replaced by an alternate antiapoptosis gene. We used the bovine herpes virus 1 (BHV-1) latency-related (LR) gene, which was previously shown to have antiapoptosis activity, for this purpose. The resulting chimeric virus, designated CJLAT, contains two complete copies of the BHV-1 LR gene (one in each viral long repeat) in place of the normal two copies of the HSV-1 LAT, on an otherwise wild-type HSV-1 strain McKrae genomic background. We report here that in both rabbits and mice reactivation of CJLAT was significantly greater than the LAT null mutant dLAT2903 (P < 0.0004 and P = 0.001, respectively) and was at least as efficient as wild-type McKrae. This strongly suggests that a BHV-1 LR gene function was able to efficiently substitute for an HSV-1 LAT gene function involved in reactivation. Although replication of CJLAT in rabbits and mice was similar to that of wild-type McKrae, CJLAT killed more mice during acute infection and caused more corneal scarring in latently infected rabbits. This suggested that the BHV-1 LR gene and the HSV-1 LAT gene are not functionally identical. However, LR and LAT both have antiapoptosis activity. These studies therefore strongly support the hypothesis that replacing LAT with an antiapoptosis gene restores the wild-type reactivation phenotype to a LAT null mutant of HSV-1 McKrae.

scholarly journals Herpes Simplex Virus Type 1 Evades the Effects of Antibody and Complement In Vivo

2002 ◽  
Vol 76 (18) ◽  
pp. 9232-9241 ◽  
Author(s):  
John M. Lubinski ◽  
Ming Jiang ◽  
Lauren Hook ◽  
Yueh Chang ◽  
Chad Sarver ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Immune Evasion ◽  
Herpes Simplex Virus Type ◽  
Complement Components ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Herpes simplex virus type 1 (HSV-1) encodes a complement-interacting glycoprotein, gC, and an immunoglobulin G (IgG) Fc binding glycoprotein, gE, that mediate immune evasion by affecting multiple aspects of innate and acquired immunity, including interfering with complement components C1q, C3, C5, and properdin and blocking antibody-dependent cellular cytotoxicity. Previous studies evaluated the individual contributions of gC and gE to immune evasion. Experiments in a murine model that examines the combined effects of gC and gE immune evasion on pathogenesis are now reported. Virulence of wild-type HSV-1 is compared with mutant viruses defective in gC-mediated C3 binding, gE-mediated IgG Fc binding, or both immune evasion activities. Eliminating both activities greatly increased susceptibility of HSV-1 to antibody and complement neutralization in vitro and markedly reduced virulence in vivo as measured by disease scores, virus titers, and mortality. Studies with C3 knockout mice indicated that other activities attributed to these glycoproteins, such as gC-mediated virus attachment to heparan sulfate or gE-mediated cell-to-cell spread, do not account for the reduced virulence of mutant viruses. The results support the importance of gC and gE immune evasion in vivo and suggest potential new targets for prevention and treatment of HSV disease.

Sign in / Sign up

Export Citation Format

Share Document