Faculty Opinions recommendation of Replication-Coupled Recruitment of Viral and Cellular Factors to Herpes Simplex Virus Type 1 Replication Forks for the Maintenance and Expression of Viral Genomes.

Author(s):  
Joel Baines ◽  
Claire Birkenheuer
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

2007 ◽  
Vol 81 (20) ◽  
pp. 10991-11004 ◽  
Author(s):  
Roger D. Everett ◽  
Jill Murray ◽  
Anne Orr ◽  
Chris M. Preston

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.


2005 ◽  
Vol 79 (8) ◽  
pp. 5078-5089 ◽  
Author(s):  
Roger D. Everett ◽  
Jill Murray

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.


2003 ◽  
Vol 77 (6) ◽  
pp. 3680-3689 ◽  
Author(s):  
Roger D. Everett ◽  
George Sourvinos ◽  
Anne Orr

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.


2004 ◽  
Vol 78 (4) ◽  
pp. 1903-1917 ◽  
Author(s):  
Roger D. Everett ◽  
George Sourvinos ◽  
Claire Leiper ◽  
J. Barklie Clements ◽  
Anne Orr

ABSTRACT Herpes simplex virus type 1 (HSV-1) has an intricate association with cellular nuclear structures known as ND10 or promyelocytic leukemia protein (PML) nuclear bodies. Parental viral genomes initially become juxtaposed to ND10, and then viral replication compartments develop from the ND10-associated genomes. Viral immediate-early (IE) regulatory protein ICP0 colocalizes with ND10 and then induces the degradation of critical ND10 component protein PML and therefore the release and dispersal of other ND10 proteins. The IE transcriptional regulatory protein ICP4 also forms foci at early times of infection, many of which are juxtaposed to ND10 and later develop into replication compartments, indicating that at least some of the initial ICP4 foci contain parental viral genomes. Here we report that the ICP4 foci also contain ICP27 and that their formation occurs extremely rapidly at locations just inside the nuclear envelope. By examining developing plaques or thinly seeded cells infected at high multiplicity, we found evidence to suggest that at least some of the ND10-viral nucleoprotein complex association could be attributed to de novo formation of ND10-like structures in response to incoming viral genomes. The ICP4 complexes associated efficiently with ND10 in cells infected with an ICP0-null mutant virus at high but not at low multiplicity, and the degree of association was reduced by the proteasome inhibitor MG132. Therefore, the interaction between viral nucleoprotein complexes and ND10 is in part due to a dynamic response by the cell. This response is modulated by functional ICP0, and cells that are productively or nonproductively infected in the absence of functional ICP0 can be distinguished by the relative locations of ICP4 foci and ND10 proteins.


2001 ◽  
Vol 120 (5) ◽  
pp. A136-A137
Author(s):  
K TSAMAKIDES ◽  
E PANOTOPOULOU ◽  
D DIMITROULOPOULOS ◽  
M CHRISTOPOULO ◽  
D XINOPOULOS ◽  
...  

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