A subset of herpes simplex virus replication genes induces DNA amplification within the host cell genome

Heilbronn, Regine; Hausen, Harald zur

doi:10.1128/jvi.63.9.3683-3692.1989

Cited by 79 publications

(41 citation statements)

References 65 publications

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“…(iii) UL8 constructs. The UL8 ORF was isolated on an EcoRI-to-XbaI fragment from pCM-UL8 (17) and inserted between the same two sites in pGEM-7Zf ϩ (Promega, Madison, Wis.). The resulting construct was designated pGM7/ UL8.…”

Section: Cells and Virusesmentioning

confidence: 99%

Characterization of nuclear structures in cells infected with herpes simplex virus type 1 in the absence of viral DNA replication

Lukonis

Weller

1996

J Virol

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Herpes simplex virus type 1 DNA replication occurs in nuclear domains termed replication compartments, which are areas of viral single-stranded DNA-binding protein (UL29) localization (M. P. Quinlan, L. B. Chen, and D. M. Knipe, Cell 36:857-868, 1984). In the presence of herpesvirus-specific polymerase inhibitors, UL29 localizes to punctate nuclear foci called prereplicative sites. Using versions of the helicase-primase complex proteins containing short peptide epitopes which can be detected in an immunofluorescence assay, we have found that the helicase-primase complex localizes to prereplicative sites and replication compartments. To determine if prereplicative site formation is dependent upon these and other essential viral replication proteins, we have studied UL29 localization in cells infected with replication-defective viruses. Cells infected with viruses that fail to express one of the three helicase-primase subunits or the origin-binding protein show a diffuse nuclear staining for UL29. However, in the presence of polymerase inhibitors, mutant-infected cells contain UL29 in prereplicative sites. Replication-defective viruses containing subtle mutations in the helicase or origin-binding proteins behaved identically to their null mutant counterparts. In contrast, cells infected with viral mutants which fail to express the polymerase protein contain prereplicative sites in the absence and presence of polymerase inhibitors. We propose that active viral polymerase prevents the formation of prereplicative sites. Models of the requirement of essential viral replication proteins in the assembly of prereplicative sites are presented.on July 10, 2020 by guest http://jvi.asm.org/ Downloaded from FIG. 3. UL29 localization in cells infected with viral mutants that fail to express UL5, UL8, UL52, or UL9. Vero cells were infected with 20 PFU of virus per cell and processed as described in Materials and Methods. (A) Cells were stained with 3-83 and fluorescein isothiocyanate-conjugated goat anti-rabbit secondary antibody. Cells were infected with the following mutants: panels A, B, and C, hr80; D, E, and F, hr99; G, H, and I, hr114. Infected cells in panels B, E, and H were treated with PAA, and those in panels C, F, and I were treated with ACG. Marker bar, 15 m. (B) hr94-infected cell doubly stained with antibodies (␣) for UL29 and BrdU. Panels A and B show the same group of hr94-infected cells doubly stained, respectively, with 3-83 (fluorescein isothiocyanate-conjugated goat anti-mouse secondary antibody) and anti-BrdU (Texas red-conjugated goat anti-mouse secondary antibody). Marker bar, 15 m.

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Section: Cells and Virusesmentioning

confidence: 99%

Characterization of nuclear structures in cells infected with herpes simplex virus type 1 in the absence of viral DNA replication

Lukonis

Weller

1996

J Virol

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“…Studies in the past concentrated on single virus infections as etiological factors of MS, whereas interactions between viruses in its pathogenesis have not been approached. Herpesviruses have been known to induce amplification of other viral genomes, as well as cellular sequences [68][69][70][71][72]. EBNA-1 enhances replication of Hepatitis C virus (HCV) [73].…”

Section: Introductionmentioning

confidence: 99%

Epstein-Barr Virus Stimulates Torque Teno Virus Replication: A Possible Relationship to Multiple Sclerosis

et al. 2012

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Viral infections have been implicated in the pathogenesis of multiple sclerosis. Epstein-Barr virus (EBV) has frequently been investigated as a possible candidate and torque teno virus (TTV) has also been discussed in this context. Nevertheless, mechanistic aspects remain unresolved. We report viral replication, as measured by genome amplification, as well as quantitative PCR of two TTV-HD14 isolates isolated from multiple sclerosis brain in a series of EBV-positive and -negative lymphoblastoid and Burkitt's lymphoma cell lines. Our results demonstrate the replication of both transfected TTV genomes up to day 21 post transfection in all the evaluated cell lines. Quantitative amplification indicates statistically significant enhanced TTV replication in the EBV-positive cell lines, including the EBV-converted BJAB line, in comparison to the EBV-negative Burkitt's lymphoma cell line BJAB. This suggests a helper effect of EBV infections in the replication of TTV. The present study provides information on a possible interaction of EBV and TTV in the etiology and progression of multiple sclerosis.

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“…The EBV initiator of replication, Zta, possesses neither positional nor sequence relationships with the HSV-1 UL9 origin-binding protein (30,31). However, we and others demonstrated previously that the core replication machinery from one viral class can substitute for the components of another viral class to mediate DNA replication in the presence of the appropriate specific initiator polypeptide and cis-acting origin sequences (31,39). To extend this approach, we attempted to search for initiator properties possessed by one or more of the HCMV auxiliary components when cotransfected with the EBV core machinery and the HCMV origin template.…”

mentioning

confidence: 95%

“…For example, in the case of HSV-1, seven distinct HSV early genes encoding the six core polypeptides, and the UL9 origin-binding protein plus two IE genes, were required to mediate HSV origin-specific DNA replication when introduced along with target origin plasmid DNA into mammalian cells by transient transfection (93). When those same essential trans-acting factors were expressed from a heterologous constitutive promoter, the minimal components required solely for origin-directed DNA amplification were identified, indicating that the IE proteins were dispensable and thus not directly needed for DNA replication itself (39). Most likely, they were critical for the transactivation of the homologous viral early promoters, as well as posttranscriptional activity, to permit efficient expression of the replication a p302 and pRL45 two encode multiple proteins and mRNA that are jointly controlled by the HCMV IE promoter and their natural context polyadenylation processing signals.…”

mentioning

confidence: 99%

Evidence that the UL84 gene product of human cytomegalovirus is essential for promoting oriLyt-dependent DNA replication and formation of replication compartments in cotransfection assays

Sarisky

Hayward

1996

J Virol

116

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The protein products of 11 viral genomic loci cooperate in a transient cotransfection assay to mediate lytic-phase DNA replication of oriLyt, the human cytomegalovirus (HCMV) origin of replication. Six of these genes have homology with the well-characterized herpes simplex virus replication genes and encode core replication machinery proteins that are typically essential for DNA synthesis. The remaining five HCMV gene loci, initially referred to as auxiliary components, include several known immediate-early (IE) transcriptional regulatory proteins as well as genes encoding functionally uncharacterized polypeptides. Some or all of the auxiliary components may be necessary in trans to replicate the HCMV oriLyt only because they are required for efficient expression or transactivation of the native early promoters and 3 processing elements included in the genomic clones. Therefore, we reassessed the requirements for the auxiliary components by adding constitutive heterologous promoters and control signals to the coding regions and carrying out transient DpnI replication assays in cotransfected Vero cells. The results revealed that in the presence of the UL69 posttranscriptional activator and the remaining auxiliary polypeptides, UL84 was the only auxiliary component that could not be omitted to obtain oriLyt-dependent DNA replication. Nevertheless, in human diploid fibroblasts, some additional auxiliary loci as well as UL84 were critical. There was also an obligatory requirement for UL84, in cooperation with two other auxiliary factors, UL112-113 and IE2, and the core machinery, to constitute the minimal HCMV proteins necessary to direct oriLyt-dependent DNA amplification. However, the Epstein-Barr virus core replication genes could substitute for the HCMV core genes, and in these circumstances, UL84 alone directed amplification of HCMV oriLyt. Moreover, there was also an absolute requirement for UL84 along with the core and other auxiliary factors for the formation of intranuclear replication compartments as assayed by immunofluorescence in transient DNA cotransfection assays. These compartments were typical of those associated with active viral DNA replication in HCMV-infected cells, they incorporated pulse-labeled bromodeoxyuridine, and their formation was both phosphonoacetic acid sensitive and oriLyt dependent. These results demonstrate that UL84 is obligatory for both intranuclear replication compartment formation and origin-dependent DNA amplification and suggest that it is a key viral component in promoting the initiation of HCMV oriLyt-directed DNA replication.

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A subset of herpes simplex virus replication genes induces DNA amplification within the host cell genome

Cited by 79 publications

References 65 publications

Characterization of nuclear structures in cells infected with herpes simplex virus type 1 in the absence of viral DNA replication

Characterization of nuclear structures in cells infected with herpes simplex virus type 1 in the absence of viral DNA replication

Epstein-Barr Virus Stimulates Torque Teno Virus Replication: A Possible Relationship to Multiple Sclerosis

Evidence that the UL84 gene product of human cytomegalovirus is essential for promoting oriLyt-dependent DNA replication and formation of replication compartments in cotransfection assays

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