This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
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 An, F.-Q.
Right arrow Articles by Renne, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by An, F.-Q.
Right arrow Articles by Renne, R.

 Previous Article  |  Next Article 

Journal of Virology, May 2006, p. 4833-4846, Vol. 80, No. 10
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.10.4833-4846.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Long-Term-Infected Telomerase-Immortalized Endothelial Cells: a Model for Kaposi's Sarcoma-Associated Herpesvirus Latency In Vitro and In Vivo{dagger}

Feng-Qi An,2 Hope Merlene Folarin,2 Nicole Compitello,2 Justin Roth,2 Stanton L. Gerson,2 Keith R. McCrae,2 Farnaz D. Fakhari,3 Dirk P. Dittmer,3 and Rolf Renne1*

Department of Molecular Genetics and Microbiology and University of Florida Shands Cancer Center, University of Florida, Gainesville, Florida 32610,1 Division of Hematology/Oncology, Case Western Reserve University, Cleveland, Ohio 44106,2 Lineberger Comprehensive Cancer Center and Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 275993

Received 12 August 2005/ Accepted 20 February 2006

Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease. Most KS tumor cells are latently infected with KSHV and are of endothelial origin. While PEL-derived cell lines maintain KSHV indefinitely, all KS tumor-derived cells to date have lost viral genomes upon ex vivo cultivation. To study KSHV latency and tumorigenesis in endothelial cells, we generated telomerase-immortalized human umbilical vein endothelial (TIVE) cells. TIVE cells express all KSHV latent genes 48 h postinfection, and productive lytic replication could be induced by RTA/Orf50. Similar to prior models, infected cultures gradually lost viral episomes. However, we also obtained, for the first time, two endothelial cell lines in which KSHV episomes were maintained indefinitely in the absence of selection. Long-term KSHV maintenance correlated with loss of reactivation in response to RTA/Orf50 and complete oncogenic transformation. Long-term-infected TIVE cells (LTC) grew in soft agar and proliferated under reduced-serum conditions. LTC, but not parental TIVE cells, formed tumors in nude mice. These tumors expressed high levels of the latency-associated nuclear antigen (LANA) and expressed lymphatic endothelial specific antigens as found in KS (LYVE-1). Furthermore, host genes, like those encoding interleukin 6, vascular endothelial growth factor, and basic fibroblast growth factor, known to be highly expressed in KS lesions were also induced in LTC-derived tumors. KSHV-infected LTCs represent the first xenograft model for KS and should be of use to study KS pathogenesis and for the validation of anti-KS drug candidates.

* Corresponding author. Mailing address: University of Florida, 1600 SW Archer Road, Gainesville, FL 32610-0232. Phone: (352) 392-9848. Fax: (352) 392-5802. E-mail: rrenne{at}ufscc.ufl.edu.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org.

Journal of Virology, May 2006, p. 4833-4846, Vol. 80, No. 10
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.10.4833-4846.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sadagopan, S., Sharma-Walia, N., Veettil, M. V., Bottero, V., Levine, R., Vart, R. J., Chandran, B. (2009). Kaposi's Sarcoma-Associated Herpesvirus Upregulates Angiogenin during Infection of Human Dermal Microvascular Endothelial Cells, Which Induces 45S rRNA Synthesis, Antiapoptosis, Cell Proliferation, Migration, and Angiogenesis. J. Virol. 83: 3342-3364 [Abstract] [Full Text]  
  • Di Bartolo, D. L., Cannon, M., Liu, Y.-F., Renne, R., Chadburn, A., Boshoff, C., Cesarman, E. (2008). KSHV LANA inhibits TGF-{beta} signaling through epigenetic silencing of the TGF-{beta} type II receptor. Blood 111: 4731-4740 [Abstract] [Full Text]  
  • Skalsky, R. L., Samols, M. A., Plaisance, K. B., Boss, I. W., Riva, A., Lopez, M. C., Baker, H. V., Renne, R. (2007). Kaposi's Sarcoma-Associated Herpesvirus Encodes an Ortholog of miR-155. J. Virol. 81: 12836-12845 [Abstract] [Full Text]  
  • Skalsky, R. L., Hu, J., Renne, R. (2007). Analysis of Viral cis Elements Conferring Kaposi's Sarcoma-Associated Herpesvirus Episome Partitioning and Maintenance. J. Virol. 81: 9825-9837 [Abstract] [Full Text]  
  • Mark, L., Spiller, O. B., Okroj, M., Chanas, S., Aitken, J. A., Wong, S. W., Damania, B., Blom, A. M., Blackbourn, D. J. (2007). Molecular Characterization of the Rhesus Rhadinovirus (RRV) ORF4 Gene and the RRV Complement Control Protein It Encodes. J. Virol. 81: 4166-4176 [Abstract] [Full Text]  
  • Punjabi, A. S., Carroll, P. A., Chen, L., Lagunoff, M. (2007). Persistent Activation of STAT3 by Latent Kaposi's Sarcoma-Associated Herpesvirus Infection of Endothelial Cells. J. Virol. 81: 2449-2458 [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»