scholarly journals Human cytomegalovirus induces JC virus DNA replication in human fibroblasts

1993 ◽  
Vol 90 (23) ◽  
pp. 11406-11410 ◽  
Author(s):  
R Heilbronn ◽  
I Albrecht ◽  
S Stephan ◽  
A Bürkle ◽  
H zur Hausen
Keyword(s):  
Dna Replication ◽  
Virus Replication ◽  
Human Cytomegalovirus ◽  
Jc Virus ◽  
Human Fibroblasts ◽  
Helper Virus ◽  
T Antigen ◽  
Virus Origin ◽  
Cultured Human Fibroblasts ◽  
Human Papovavirus

JC virus, a human papovavirus, is the causative agent of the demyelinating brain disease progressive multifocal leucoencephalopathy (PML). PML is a rare but fatal disease which develops as a complication of severe immunosuppression. Latent JC virus is harbored by many asymptomatic carriers and is transiently reactivated from the latent state upon immunosuppression. JC virus has a very restricted host range, with human glial cells being the only tissue in which it can replicate at reasonable efficiency. Evidence that latent human cytomegalovirus is harbored in the kidney similar to latent JC virus led to the speculation that during episodes of impaired immunocompetence, cytomegalovirus might serve as helper virus for JC virus replication in otherwise nonpermissive cells. We show here that cytomegalovirus infection indeed leads to considerable JC virus DNA replication in cultured human fibroblasts that are nonpermissive for the replication of JC virus alone. Cytomegalovirus-mediated JC virus replication is dependent on the JC virus origin of replication and T antigen. Ganciclovir-induced inhibition of cytomegalovirus replication is associated with a concomitant inhibition of JC virus replication. These results suggest that reactivation of cytomegalovirus during episodes of immunosuppression might lead to activation of latent JC virus, which would enhance the probability of subsequent PML development. Ganciclovir-induced repression of both cytomegalovirus and JC virus replication may form the rational basis for the development of an approach toward treatment or prevention of PML.

Glycoprotein gpTRL10 of human cytomegalovirus is dispensable for virus replication in human fibroblasts

2004 ◽  
Vol 149 (3) ◽  
pp. 495-506 ◽  
Author(s):  
S. Spaderna ◽  
G. Hahn ◽  
M. Mach
Keyword(s):  
Virus Replication ◽  
Human Cytomegalovirus ◽  
Human Fibroblasts

scholarly journals Insights into the Initiation of JC Virus DNA Replication Derived from the Crystal Structure of the T-Antigen Origin Binding Domain

2014 ◽  
Vol 10 (2) ◽  
pp. e1003966 ◽  
Author(s):  
Gretchen Meinke ◽  
Paul J. Phelan ◽  
Radha Kalekar ◽  
Jong Shin ◽  
Jacques Archambault ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Dna Replication ◽  
Jc Virus ◽  
T Antigen ◽  
Binding Domain

Large T-Antigen and Sequences within the Regulatory Region of JC Virus Both Contribute to the Features of JC Virus DNA Replication

Virology ◽  
1993 ◽  
Vol 197 (2) ◽  
pp. 537-548 ◽  
Author(s):  
Elisabeth Sock ◽  
Michael Wegner ◽  
Elizabeth A. Fortunato ◽  
Friedrich Grummt
Keyword(s):  
Dna Replication ◽  
Jc Virus ◽  
Regulatory Region ◽  
T Antigen ◽  
Large T Antigen

scholarly journals Detection of human cytomegalovirus DNA replication in non-permissive Vero and 293 cells

2003 ◽  
Vol 84 (3) ◽  
pp. 639-645 ◽  
Author(s):  
Victoria Ellsmore ◽  
G. Gordon Reid ◽  
Nigel D. Stow
Keyword(s):  
Dna Replication ◽  
Dna Synthesis ◽  
Human Cytomegalovirus ◽  
Human Fibroblasts ◽  
Cell Types ◽  
Vero Cells ◽  
Progeny Virus ◽  
Viral Dna ◽  
Viral Origin ◽  
293 Cells

Human cytomegalovirus (HCMV) displays an exceptionally restricted host range in tissue culture with human fibroblasts being the principal fully permissive system. Nevertheless, immediate early (IE) proteins are expressed following infection of many non-permissive cell types of human, simian and murine origin, and viral origin-dependent DNA synthesis has been reconstituted by transfection of plasmids into Vero cells, a non-permissive line from African green monkey. We have examined the accumulation of HCMV strain AD169 DNA, and the replication of transfected HCMV origin-containing plasmids, in infected Vero and human embryonic kidney 293 cells, which were previously reported to express the major IE protein in a small proportion of infected cells but to be non-permissive for viral DNA synthesis. In Vero cells accumulation of origin-containing plasmid but not viral DNA occurred, whilst in 293 cells both DNAs accumulated. Immunofluorescence experiments indicated that following infection with 3 p.f.u. per cell, a small fraction of both cell types expressed the UL44 DNA replication protein. Neither cell line, however, supported the generation of infectious progeny virus. These results suggest that IE proteins expressed in Vero and 293 cells can induce the synthesis of early proteins capable of functioning in viral DNA replication, but there is a failure in later events on the pathway to infectious virus production. This provides further support for transfected Vero cells being a valid system in which to study HCMV DNA synthesis, and suggests that 293 cells may also prove useful in similar experiments.

scholarly journals Human Cytomegalovirus Infection Leads to Accumulation of Geminin and Inhibition of the Licensing of Cellular DNA Replication

2003 ◽  
Vol 77 (4) ◽  
pp. 2369-2376 ◽  
Author(s):  
Nilima Biswas ◽  
Veronica Sanchez ◽  
Deborah H. Spector
Keyword(s):  
Dna Replication ◽  
Host Cell ◽  
Human Cytomegalovirus ◽  
Human Fibroblasts ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Early Protein ◽  
Infected Cells ◽  
Mcm Proteins ◽  
Cellular Dna

ABSTRACT Previous studies have shown that infection of G0-synchronized human fibroblasts by human cytomegalovirus (HCMV) results in a block to cellular DNA synthesis. In this study, we have examined the effect of viral infection on the formation of the host cell DNA prereplication complex (pre-RC). We found that the Cdc6 protein level was significantly upregulated in the virus-infected cells and that there was a delay in the expression of the Mcm family of proteins. The loading of the Mcm proteins onto the DNA pre-RC complex also appeared to be defective in the virus-infected cells. This inhibition of DNA replication licensing was associated with the accumulation of geminin, a replication inhibitor. Cdt1, which participates in the loading of the Mcm proteins, was also downregulated and modified differentially in the infected cells. Early viral gene expression was sufficient for the virus-induced alteration of the pre-RC, and the immediate-early protein IE1 was not required. These studies show that the inhibition of replication licensing in HCMV-infected cells is one of the multiple pathways by which the virus dysregulates the host cell cycle.

scholarly journals JC Virus Small t Antigen Binds Phosphatase PP2A and Rb Family Proteins and Is Required for Efficient Viral DNA Replication Activity

PLoS ONE ◽  
2010 ◽  
Vol 5 (5) ◽  
pp. e10606 ◽  
Author(s):  
Brigitte Bollag ◽  
Catherine A. Hofstetter ◽  
Marta M. Reviriego-Mendoza ◽  
Richard J. Frisque
Keyword(s):  
Dna Replication ◽  
Jc Virus ◽  
T Antigen ◽  
Viral Dna ◽  
Viral Dna Replication ◽  
Small T Antigen ◽  
Replication Activity

Internalization of Exogenous Human Immunodeficiency Virus-1 Protein, Tat, by KG-1 Oligodendroglioma Cells Followed by Stimulation of DNA Replication Initiated at the JC Virus Origin

2004 ◽  
Vol 23 (12) ◽  
pp. 858-867 ◽  
Author(s):  
Dianne C. Daniel ◽  
Yayoi Kinoshita ◽  
M. Aamir Khan ◽  
Luis Del Valle ◽  
Kamel Khalili ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dna Replication ◽  
Jc Virus ◽  
Virus Origin ◽  
Immunodeficiency Virus ◽  
Human Immunodeficiency Virus 1 ◽  
Stimulation Of

scholarly journals Human Cytomegalovirus DNA Replication Requires Transcriptional Activation via an IE2- and UL84-Responsive Bidirectional Promoter Element within oriLyt

2004 ◽  
Vol 78 (21) ◽  
pp. 11664-11677 ◽  
Author(s):  
Yiyang Xu ◽  
Sylvia A. Cei ◽  
Alicia Rodriguez Huete ◽  
Kelly S. Colletti ◽  
Gregory S. Pari
Keyword(s):  
Dna Replication ◽  
Human Cytomegalovirus ◽  
Transcriptional Activation ◽  
Human Fibroblasts ◽  
Simian Virus 40 ◽  
Fibroblast Cell ◽  
Bidirectional Promoter ◽  
Simian Virus ◽  
Lytic Replication ◽  
Early Protein

ABSTRACT Amplification of the human cytomegalovirus (HCMV) lytic origin (oriLyt) in human fibroblasts is dependent upon six core replication proteins and UL84, IE2, and UL36-38. Using a telomerase-immortalized human fibroblast cell line (T-HFs), oriLyt-dependent DNA replication no longer required the gene products of UL36-38. To determine the role of IE2 in DNA replication in human fibroblasts, we examined potential IE2-binding sites within HCMV oriLyt. We now show that a strong bidirectional promoter (oriLytPM) (nucleotides 91754 to 92030) is located in the previously identified core region of the origin and is required for efficient amplification of oriLyt. It was determined that a 14-bp novel DNA motif (oriLyt promoter activation element), which was initially identified as a binding element for the immediate-early protein IE2, was essential for oriLytPM activity. In Vero cells the oriLytPM was constitutively active and strongly repressed by IE2, but it was reactivated by UL84. In contrast, transfection of the oriLytPM into human fibroblasts resulted in a very low basal level of promoter activity that was dramatically up-regulated upon infection with HCMV. Cotransfection assays demonstrated that the transfection of UL84 along with IE2 transactivated the oriLytPM in human fibroblasts. Further activation was observed upon cotransfection of the set of plasmids expressing the entire replication complex. Efficient oriLyt amplification in the absence of IE2 in human fibroblasts was observed by replacing the oriLytPM with the simian virus 40 early promoter. Under these conditions, however, UL84 was still required for amplification of oriLyt. These results suggest that the mechanism of initiation of HCMV lytic replication in part involves transcriptional activation.

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