This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Safak, M.
Right arrow Articles by Khalili, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Safak, M.
Right arrow Articles by Khalili, K.

 Previous Article  |  Next Article 

Journal of Virology, April 2002, p. 3828-3838, Vol. 76, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.8.3828-3838.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Functional Interaction between JC Virus Late Regulatory Agnoprotein and Cellular Y-Box Binding Transcription Factor, YB-1

Mahmut Safak, Beata Sadowska, Robert Barrucco, and Kamel Khalili*

Laboratory of Molecular Neurovirology, Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122

Received 19 July 2001/ Accepted 23 October 2001

Human polyomavirus JC virus (JCV) is a causative agent of progressive multifocal leukoencephalopathy which results from lytic infection of glial cells. Although significant progress has been made in understanding the regulation of JCV gene transcription, the mechanism(s) underlying the viral lytic cycle remains largely unknown. We recently reported that the JCV late auxiliary Agnoprotein may have a regulatory role in JCV gene transcription and replication. Here, we investigated its regulatory function in viral gene transcription through its physical and functional interaction with YB-1, a cellular transcription factor which contributes to JCV gene expression in glial cells. Time course studies revealed that Agnoprotein is first detected at day 3 postinfection and that its level increased during the late stage of the infection cycle. Agnoprotein is mainly localized to the cytoplasmic compartment of the infected cell, with high concentrations found in the perinuclear region. While the position of Agnoprotein throughout the infection cycle remained relatively unaltered, the subcellular distribution of YB-1 between the cytoplasm and nucleus changed. Results from coimmunoprecipitation and glutathione S-transferase pull-down experiments revealed that Agnoprotein physically interacts with YB-1 and that the amino-terminal region of Agnoprotein, between residues 1 and 36, is critical for this association. Further investigation of this interaction by functional assays demonstrated that Agnoprotein negatively regulates YB-1-mediated gene transcription and that the region corresponding to residues 1 to 36 of Agnoprotein is important for the observed regulatory event. Taken together, these data demonstrate that the interaction of the viral late regulatory Agnoprotein and cellular Y-box binding factor YB-1 modulates transcriptional activity of JCV promoters.

* Corresponding author. Mailing address: Laboratory of Molecular Neurovirology, Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, 1900 North 12th St., 015-96, Room 203, Philadelphia, PA 19122. Phone: (215) 204-0678. Fax: (215) 204-0679. E-mail: kkhalili{at}astro.temple.edu.

Journal of Virology, April 2002, p. 3828-3838, Vol. 76, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.8.3828-3838.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • White, M. K., Safak, M., Khalili, K. (2009). Regulation of Gene Expression in Primate Polyomaviruses. J. Virol. 83: 10846-10856 [Abstract] [Full Text]  
  • Kaniowska, D., Kaminski, R., Amini, S., Radhakrishnan, S., Rappaport, J., Johnson, E., Khalili, K., Del Valle, L., Darbinyan, A. (2006). Cross-Interaction between JC Virus Agnoprotein and Human Immunodeficiency Virus Type 1 (HIV-1) Tat Modulates Transcription of the HIV-1 Long Terminal Repeat in Glial Cells.. J. Virol. 80: 9288-9299 [Abstract] [Full Text]  
  • Miller, M. M., Halbig, K., Cruz-Reyes, J., Read, L. K. (2006). RBP16 stimulates trypanosome RNA editing in vitro at an early step in the editing reaction. RNA 12: 1292-1303 [Abstract] [Full Text]  
  • Sariyer, I. K., Akan, I., Palermo, V., Gordon, J., Khalili, K., Safak, M. (2006). Phosphorylation Mutants of JC Virus Agnoprotein Are Unable To Sustain the Viral Infection Cycle.. J. Virol. 80: 3893-3903 [Abstract] [Full Text]  
  • Darbinyan, A., Siddiqui, K. M., Slonina, D., Darbinian, N., Amini, S., White, M. K., Khalili, K. (2004). Role of JC Virus Agnoprotein in DNA Repair. J. Virol. 78: 8593-8600 [Abstract] [Full Text]  
  • Radhakrishnan, S., Otte, J., Enam, S., Del Valle, L., Khalili, K., Gordon, J. (2003). JC Virus-Induced Changes in Cellular Gene Expression in Primary Human Astrocytes. J. Virol. 77: 10638-10644 [Abstract] [Full Text]  
  • Kim, J., Woolridge, S., Biffi, R., Borghi, E., Lassak, A., Ferrante, P., Amini, S., Khalili, K., Safak, M. (2003). Members of the AP-1 Family, c-Jun and c-Fos, Functionally Interact with JC Virus Early Regulatory Protein Large T Antigen. J. Virol. 77: 5241-5252 [Abstract] [Full Text]  
  • PELLETIER, M., READ, L. K. (2003). RBP16 is a multifunctional gene regulatory protein involved in editing and stabilization of specific mitochondrial mRNAs in Trypanosoma brucei. RNA 9: 457-468 [Abstract] [Full Text]  
  • Sadowska, B., Barrucco, R., Khalili, K., Safak, M. (2002). Regulation of Human Polyomavirus JC Virus Gene Transcription by AP-1 in Glial Cells. J. Virol. 77: 665-672 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»