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Transformation of primary human endothelial cells by Kaposi's sarcoma-associated herpesvirus

Nature volume 394, pages 588–592 (1998)Cite this article

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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Figure 1: Infection of BMECs and HUVECs with KSHV.
Figure 2: Presence of KSHV DNA in infected endothelial cells.
Figure 3: Detection of KSHV antigens in infected BMEC and HUVEC cells by immunofluorescence assay.
Figure 4: Paracrine effects in uninfected HUVEC cells by conditioned medium from KSHV-positive endothelial cell cultures.
Figure 5: Transformation of KSHV-infected HUVECs.

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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

  1. 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

  2. Department of Pathology, Division of Hematology-Oncology, Department of Medicine, Cornell University Medical College, New York, 10021, New York, USA

    Shahin Rafii

  3. Dipartimento di Medicina Interna, Universita' di Cagliari, Cagliari, 09100, Italy

    Ornella Flore

  4. 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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  1. Ornella Flore
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  2. Shahin Rafii
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Correspondence to Ethel 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

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