Quiescent viral genomes in human fibroblasts after infection with herpes simplex virus type 1 Vmw65 mutants

1995 ◽  
Vol 76 (6) ◽  
pp. 1417-1431 ◽  
Author(s):  
D. R. S. Jamieson ◽  
L. H. Robinson ◽  
J. I. Daksis ◽  
M. J. Nicholl ◽  
C. M. Preston
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Human Fibroblasts ◽  
Viral Genomes ◽  
Simplex Virus

scholarly journals Herpes Simplex Virus Type 1 Genomes Are Associated with ND10 Nuclear Substructures in Quiescently Infected Human Fibroblasts

2007 ◽  
Vol 81 (20) ◽  
pp. 10991-11004 ◽  
Author(s):  
Roger D. Everett ◽  
Jill Murray ◽  
Anne Orr ◽  
Chris M. Preston
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Human Fibroblasts ◽  
Lytic Infection ◽  
Viral Genomes ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Herpes simplex virus type 1 (HSV-1) genomes become associated with structures related to cellular nuclear substructures known as ND10 or promyelocytic leukemia nuclear bodies during the early stages of lytic infection. This paper describes the relationship between HSV-1 genomes and ND10 in human fibroblasts that maintain the viral genomes in a quiescent state. We report that quiescent HSV-1 genomes detected by fluorescence in situ hybridization (FISH) are associated with enlarged ND10-like structures, frequently such that the FISH-defined viral foci are apparently enveloped within a sphere of PML and other ND10 proteins. The number of FISH viral foci in each quiescently infected cell is concordant with the input multiplicity of infection, with each structure containing no more than a small number of viral genomes. A proportion of the enlarged ND10-like foci in quiescently infected cells contain accumulations of the heterochromatin protein HP1 but not other common markers of heterochromatin such as histone H3 di- or trimethylated on lysine residue 9. Many of the virally induced enlarged ND10-like structures also contain concentrations of conjugated ubiquitin. Quiescent infections can be established in cells that are highly depleted for PML. However, during the initial stages of establishment of a quiescent infection in such cells, other ND10 proteins (Sp100, hDaxx, and ATRX) are recruited into virally induced foci that are likely to be associated with HSV-1 genomes. These observations illustrate that the intimate connections between HSV-1 genomes and ND10 that occur during lytic infection also extend to quiescent infections.

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.

Sphingolipid Metabolism during Infection of Human Fibroblasts by Herpes Simplex Virus Type 1

Intervirology ◽  
1984 ◽  
Vol 21 (2) ◽  
pp. 70-76 ◽  
Author(s):  
William L. Steinhart ◽  
Jordan S. Busch ◽  
Peter Oettgen ◽  
John L. Howland
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Human Fibroblasts ◽  
Sphingolipid Metabolism ◽  
Simplex Virus

scholarly journals Activation of cellular interferon-responsive genes after infection of human cells with herpes simplex virus type 1

2000 ◽  
Vol 81 (9) ◽  
pp. 2215-2218 ◽  
Author(s):  
Mary Jane Nicholl ◽  
Laurence H. Robinson ◽  
Chris M. Preston
Keyword(s):  
Gene Expression ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Human Fibroblasts ◽  
Interferon Α ◽  
Simplex Virus ◽  
Hsv 1

Previous studies have shown that infection of human fibroblasts with human cytomegalovirus (HCMV) results in activation of cellular interferon-responsive gene expression. We demonstrate here that infection of human fibroblasts with herpes simplex virus type 1 (HSV-1) in the absence of de novo protein synthesis also induces the expression of interferon-responsive genes. Five genes tested (encoding ISG54, IFI56, ISG15, 9-27 and MxA) were activated by infection with HSV-1, although the degree of response varied between the individual genes. HSV-1 was a less efficient inducer than HCMV. The effect was a consequence of binding of the virus particle to the cell surface or of the presence of virion components within the infected cell. Induction was mediated by a pathway other than the mechanism through which interferon-α mediates its effects on cellular gene expression.

scholarly journals ND10 Components Relocate to Sites Associated with Herpes Simplex Virus Type 1 Nucleoprotein Complexes during Virus Infection

2005 ◽  
Vol 79 (8) ◽  
pp. 5078-5089 ◽  
Author(s):  
Roger D. Everett ◽  
Jill Murray
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Infection ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Dna Viruses ◽  
Viral Genomes ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Infections with DNA viruses commonly result in the association of viral genomes and replication compartments with cellular nuclear substructures known as promyelocytic leukemia protein (PML) nuclear bodies or ND10. While there is evidence that viral genomes can associate with preexisting ND10, we demonstrate in this study by live-cell microscopy that structures resembling ND10 form de novo and in association with viral genome complexes during the initial stages of herpes simplex virus type 1 (HSV-1) infection. Consistent with previous studies, we found that the major ND10 proteins PML, Sp100, and hDaxx are exchanged very rapidly between ND10 foci and the surrounding nucleoplasm in live cells. The dynamic nature of the individual protein molecule components of ND10 provides a mechanism by which ND10 proteins can be recruited to novel sites during virus infection. These observations explain why the genomes and replication compartments of DNA viruses that replicate in the cell nucleus are so commonly found in association with ND10. These findings are discussed with reference to the nature, location, and potential number of HSV-1 prereplication compartments and to the dynamic aspects of HSV-1 genomes and viral products during the early stages of lytic infection.

scholarly journals Recruitment of Herpes Simplex Virus Type 1 Transcriptional Regulatory Protein ICP4 into Foci Juxtaposed to ND10 in Live, Infected Cells

2003 ◽  
Vol 77 (6) ◽  
pp. 3680-3689 ◽  
Author(s):  
Roger D. Everett ◽  
George Sourvinos ◽  
Anne Orr
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Nuclear Bodies ◽  
Viral Genomes ◽  
Infected Cells ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT At the early stages of herpes simplex virus type 1 (HSV-1) infection, parental viral genomes have a tendency to become juxtaposed to cellular nuclear structures known as PML (promyelocytic leukemia) nuclear bodies or ND10, while the immediate-early (IE) protein ICP0 precisely colocalizes with these structures. Previous indirect-immunofluorescence studies observed that the HSV-1 transcriptional regulator ICP4 has a mainly diffuse nuclear distribution early in infection and is later recruited into viral replication compartments. We have constructed HSV-1 variants expressing ICP4 and ICP0 linked to ECFP and EYFP, respectively, both singly and in combination. Coupled with an efficient method of expressing autofluorescent PML in ND10, we have studied the dynamics of ICP0, ICP4, and ND10 in live, infected cells. The greater sensitivity and lower background signals in live cells revealed that early in infection, ICP4 forms discrete foci, some of which are juxtaposed to ND10, while ICP0 was found to colocalize precisely with PML. As expected from these results, using a double-labeled virus, we observed that foci of ICP0 and ICP4 were also juxtaposed but not colocalized early in infection. Some of the ICP4 foci must have contained parental viral genomes, because they developed into replication compartments. We propose that a proportion of the ND10-associated ICP4 foci represent ICP4 molecules being recruited onto parental viral genomes, a process likely to be a critical step early in lytic infection. These results may be analogous to the localization of IE1 and IE2 during human cytomegalovirus infection, suggesting a principle common to the alpha- and betaherpesviruses.

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