scholarly journals Expression of human polyomavirus JC T antigen by an adenovirus hybrid vector and its binding to DNA sequences encompassing the JC virus origin of DNA replication

1995 ◽  
Vol 76 (1) ◽  
pp. 83-92 ◽  
Author(s):  
O. Windl ◽  
K. Dorries

2004 ◽  
Vol 78 (7) ◽  
pp. 3462-3469 ◽  
Author(s):  
Luis Del Valle ◽  
Sahnila Enam ◽  
Cesar Lara ◽  
Judith Miklossy ◽  
Kamel Khalili ◽  
...  

ABSTRACT B lymphocytes are known as a potential site for latency and reactivation of the human neurotropic polyomavirus, JC virus (JCV). In light of recent studies on the oncogenicity of JCV and the transforming ability of the JCV early protein, T antigen, we investigated the association of JCV with B-cell lymphomas of the central nervous system. Examination of 27 well-characterized clinical specimens by gene amplification and immunohistochemistry revealed the presence of DNA sequences corresponding to the JCV early genome and the late Agnoprotein in 22 samples and the JCV late genome encoding the viral capsid proteins in 8 samples. Expression of T antigen and that of Agnoprotein by immunohistochemistry were each detected in six specimens. No evidence of the production of viral capsid proteins was observed, ruling out productive infection of JCV in the tumor cells. The results from laser capture microdissection verified the presence of JCV T-antigen sequences in tumor cells with positive immunoreactivity to antibodies against the viral proteins T antigen and Agnoprotein. Due to previous reports demonstrating an association of the Epstein-Barr virus (EBV) with transformation of B lymphocytes, EBV DNA sequences and the EBV transforming protein, latent membrane protein 1 (LMP1), were analyzed in parallel. EBV LMP1 DNA sequences were detected in 16 of 23 samples, and LMP1 expression was detected in 16 samples, 5 of which exhibited positive immunoreactivity to JCV proteins. Double labeling demonstrated coexpression of JCV T antigen and EBV LMP1 in the same cells. The detection of the JCV genome in large numbers of B-cell lymphomas and its coexistence with EBV suggest a potential role for JCV in the pathogenesis of primary CNS lymphoma.





1993 ◽  
Vol 90 (23) ◽  
pp. 11406-11410 ◽  
Author(s):  
R Heilbronn ◽  
I Albrecht ◽  
S Stephan ◽  
A Bürkle ◽  
H zur Hausen

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.



1999 ◽  
Vol 73 (12) ◽  
pp. 10146-10157 ◽  
Author(s):  
Mahmut Safak ◽  
Gary L. Gallia ◽  
Sameer A. Ansari ◽  
Kamel Khalili

ABSTRACT Y-box binding protein YB-1 is a member of a family of DNA and RNA binding proteins which have been shown to affect gene expression at both the transcriptional and translational levels. We have previously shown that YB-1 modulates transcription from the promoters of the ubiquitous human polyomavirus JC virus (JCV). Here we investigate the physical and functional interplay between YB-1 and the viral regulatory protein large T antigen (T-antigen), using JCV as a model system. Results of mobility band shift assays demonstrated that the efficiency of binding of YB-1 to a 23-bp single-stranded viral target sequence was significantly increased when T-antigen was included in the binding reaction mixture. Affinity chromatography and coimmunoprecipitation assays demonstrated that YB-1 and T-antigen physically interact with each other. Additionally, results of transcription studies demonstrated that these two proteins interact functionally on the JCV early and late gene promoters. Whereas ectopic expression of YB-1 and T-antigen results in synergistic transactivation of the viral late promoter, YB-1 alleviates T-antigen-mediated transcriptional suppression of the viral early promoter activity. Furthermore, we have localized, through the use of a series of deletion mutants, the sequences of these proteins which are important for their interaction. The T-antigen-interacting region of YB-1 is located in the cold shock domain of YB-1 and its immediate flanking sequences, and the YB-1-interacting domain of T-antigen maps to the carboxy-terminal half of T-antigen. Results of transient transfection assays with various YB-1 mutants and T-antigen expression constructs confirm the specificity of the functional interaction between YB-1 and T-antigen. Taken together, these data demonstrate that the cellular factor YB-1 and the viral regulatory protein T-antigen interact both physically and functionally and that this interaction modulates transcription from the JCV promoters.



2005 ◽  
Vol 206 (1) ◽  
pp. 35-46 ◽  
Author(s):  
Joanna Trojanek ◽  
Sidney Croul ◽  
Thu Ho ◽  
Jin Ying Wang ◽  
Armine Darbinyan ◽  
...  




Biochemistry ◽  
1998 ◽  
Vol 37 (44) ◽  
pp. 15345-15352 ◽  
Author(s):  
Shu-Gui Huang ◽  
Klaus Weisshart ◽  
Ilka Gilbert ◽  
Ellen Fanning


Nature ◽  
1989 ◽  
Vol 338 (6217) ◽  
pp. 658-662 ◽  
Author(s):  
Iris A. Mastrangelo ◽  
Paul V. C. Hough ◽  
Joseph S. Wall ◽  
Mark Dodson ◽  
Frank B. Dean ◽  
...  


1986 ◽  
Vol 67 (8) ◽  
pp. 1733-1739 ◽  
Author(s):  
C. W. Mandl ◽  
R. J. Frisque


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