Transformation of primary human endothelial cells by Kaposi's sarcoma-associated herpesvirus (original) (raw)
- Letter
- Published: 06 August 1998
- Shahin Rafii2,
- Scott Ely1,
- John J. O'Leary1,4,
- Elizabeth M. Hyjek1 &
- …
- Ethel Cesarman1
Nature volume 394, pages 588–592 (1998)Cite this article
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Abstract
Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8, is invariably present in Kaposi's sarcoma lesions1,2. KSHV contains several viral oncogenes and serological evidence suggests that KSHV infection is necessary for the development of Kaposi's sarcoma, but cellular transformation by this virus has not so far been demonstrated. KSHV is found in the microvascular endothelial cells in Kaposi's sarcoma lesions and in the spindle ‘tumour’ cells3,4, which are also thought to be of endothelial origin. Here we investigate the biological consequences of infecting human primary endothelial cells with purified KSHV particles. We find that infection causes long-term proliferation and survival of these cells, which are associated with the acquisition of telomerase activity and anchorage-independent growth. KSHV was present in only a subset of cells, and paracrine mechanisms were found to be responsible for the survival of uninfected cells. Their survival may have been mediated by upregulation of a receptor for vascular endothelial growth factor. Our results indicate that transformation of endothelial cells by KSHV, as well as paracrine mechanisms that are induced by this virus, may be critical in the pathogenesis of Kaposi's sarcoma.
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References
- Chang, Y. et al. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 266, 1865–1869 (1994).
Article ADS CAS Google Scholar - Moore, P. S. & Chang, Y. Detection of herpesvirus-like DNA sequences in Kaposi's sarcoma in patients with and those without HIV infection. N. Engl. J. Med. 332, 1181–1185 (1995).
Article CAS Google Scholar - Boshoff, C. et al. Kaposi's sarcoma-associated herpesvirus infects endothelial and spindle cells. Nature Med. 1, 1274–1278 (1995).
Article CAS Google Scholar - Reed, J. A. et al. Demonstration of Kaposi's sarcoma-associated herpesvirus cyclin D homolog in cutaneous Kaposi's sarcoma by colorimetric in situ hybridization using a catalyzed signal amplification system. Blood(in the press).
- Arvanitakis, L. et al. Establishment and characterization of a primary effusion (body cavity-based) lymphoma cell line (BC-3) harboring Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) in the absence of Epstein–Barr virus. Blood 88, 2648–2654 (1996).
CAS PubMed Google Scholar - Renne, R. et al. Lytic growth of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in culture. Nature Med. 2, 342–346 (1996).
Article CAS Google Scholar - Miller, G. et al. Selective switch between latency and lytic replication of Kaposi's sarcoma herpesvirus and Epstein–Barr virus in dually infected body cavity lymphoma cells. J. Virol. 71, 314–324 (1997).
CAS PubMed PubMed Central Google Scholar - Rafii, S. et al. Human bone marrow microvascular endothelial support long term proliferation and differentiation of myeloid and megakaryocytic progenitors. Blood 86, 3353–3363 (1995).
CAS PubMed Google Scholar - Watanabe, Y. & Dvorak, H. F. Vascular permeability factor/vascular endothelial growth factor inhibits anchorage-disruption-induced aposptosis in microvessel endothelial cells by inducing scaffold formation. Exp. Cell Res. 233, 340–349 (1997).
Article CAS Google Scholar - Cesarman, E. et al. Kaposi's sarcoma associated herpesvirus (KSHV/HHV-8) contains G protein-coupled receptor and cyclin D homologs which are expressed in Kaposi's sarcoma and malignant lymphoma. J. Virol. 70, 8218–8223 (1996).
CAS PubMed PubMed Central Google Scholar - O'Leary, J. PCR In-situ Hybridization. 1–53-86 (IRL, Oxford University Press, Oxford, (1997)).
Google Scholar - Ruby Chan, S., Bloomer, C. & Chandran, B. Identification and characterization of human herpesvirus-8 lytic cycle associated ORF 59 protein and the encoding cDNA by monoclonal antibody. Virology 240, 118–126 (1998).
Article Google Scholar - Hewett, P. W. & Murray, J. C. Coexpression of flt-1, flt-4 and KDR in freshly isolated and cultured human endothelial cells. Biochem. Biophys. Res. Commun. 221, 697–702 (1996).
Article CAS Google Scholar - Rienke, U., Burlington, H., Cronkite, E. P. & Laissue, J. Hayflick's hypothesis: an approach to in vivo testing. Fed. Proc. 34, 71–75 (1975).
Google Scholar - Kim, N. W. et al. Specific association of human telomerase activity with immortal cells and cancer. Science 266, 2011–2015 (1994).
Article ADS CAS Google Scholar - Mieczyslaw, A. P. et al. Detection of telomerase activity in human cells and tumors by a telomeric repeat amplification protocol (TRAP). Meth. Cell Sci. 17, 1–15 (1995).
Article Google Scholar - Kennedy, M. M. et al. HHV8 and Kaposi's sarcoma: a time cohort study. Mol. Pathol. 50, 96–100 (1997).
Article CAS Google Scholar - Rhoads, R. E. Optimization of the annealing temperature for DNA amplification in vitro. Nucleic Acids Res. 18, 6409–6412 (1990).
Article Google Scholar - Kedes, D. H. et al. The seroepidemiology of human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus): Distribution of infection in KS risk groups and evidence for sexual transmission. Nature Med. 2, 918–924 (1996).
Article CAS Google Scholar - Kim, N. W. & Wu, F. Advances in quantification and characterization of telomerase activity by the telomeric repeat amplification protocol (TRAP). Nucleic Acids Res. 25, 2595–2597 (1997).
Article CAS Google Scholar
Acknowledgements
We thank S. Chen-Kiang, D. Knowles, M. C. Gershengorn and E. Mesri for their suggestions; B. Chandran and S.-J. Gao for antibodies against lytic antigens; P. Pellet for positive controls CMB and HHV-6; L. Friedman, S. Nikolovska, B. Ferris, G. Lam, A. J. Naiyer, S. Diana, I. Silva and V.Uhlmann for technical help; and S. Picton and K. Lohman at Perkin Elmer Applied Biosystems.
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Authors and Affiliations
- Department of Pathology, Department of Medicine, Cornell University Medical College, New York, 10021, New York, USA
Ornella Flore, Scott Ely, John J. O'Leary, Elizabeth M. Hyjek & Ethel Cesarman - Department of Pathology, Division of Hematology-Oncology, Department of Medicine, Cornell University Medical College, New York, 10021, New York, USA
Shahin Rafii - Dipartimento di Medicina Interna, Universita' di Cagliari, Cagliari, 09100, Italy
Ornella Flore - Departments of Pathology, The Coombe Women's Hospital and St James's Hospital Dublin, and Trinity College Dublin, Ireland
John J. O'Leary
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Correspondence toEthel Cesarman.
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Flore, O., Rafii, S., Ely, S. et al. Transformation of primary human endothelial cells by Kaposi's sarcoma-associated herpesvirus.Nature 394, 588–592 (1998). https://doi.org/10.1038/29093
- Received: 30 March 1998
- Accepted: 11 June 1998
- Issue Date: 06 August 1998
- DOI: https://doi.org/10.1038/29093