TRANSFORMATION OF PRIMARY HUMAN ENDOTHELIAL-CELLS BY KAPOSIS-SARCOMA-ASSOCIATED HERPESVIRUS

Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8 , is invariably present in Kaposi's sarcoma lesions(1,2) KSHV contains several viral oncogenes and serological evidence suggests that KSHV i nfection is necessary for the development of Kaposi's sarcoma, but cel lular transformation by this virus has not so far been demonstrated. K SHV is found in the microvascular endothelial cells in Kaposi's sarcom a lesions and in the spindle 'tumour' cells(3,4), which are also thoug ht to be of endothelial origin. Here we investigate the biological con sequences of infecting human primary endothelial cells with purified K SHV particles. We find that infection causes long-term proliferation a nd survival of these cells, which are associated with the acquisition of telomerase activity and anchorage-independent growth. KSHV was pres ent in only a subset of cells, and paracrine mechanisms were found to be responsible for the survival of uninfected cells. Their survival ma y have been mediated by upregulation of a receptor for vascular endoth elial growth factor. Our results indicate that transformation of endot helial cells by KSHV, as well as paracrine mechanisms that are induced by this virus, may be critical in the pathogenesis of Kaposi's sarcom a.