DISTINCT BIOLOGY OF KAPOSIS SARCOMA-ASSOCIATED HERPESVIRUS FROM PRIMARY LESIONS AND BODY CAVITY LYMPHOMAS

The DNA sequence for Kaposi's sarcoma-associated herpesvirus was origi nally detected in Kaposi's sarcoma biopsy specimens. Since its discove ry, it has been possible to detect virus in cell lines established fro m AIDS-associated body cavity-based B-cell lymphoma and to propagate v irus from primary Kaposi's sarcoma lesions in a human renal embryonic cell line, 293. In this study, we analyzed the infectivity of Kaposi's sarcoma-associated herpesvirus produced from these two sources. Viral isolates from cultured cutaneous primary KS cells was transmitted to an Epstein-Barr virus-negative Burkitt's B-lymphoma cell line, Louckes , and compared to virus induced from a body cavity-based B-cell lympho ma cell line. While propagation of body cavity-based B-cell lymphoma-d erived virus was not observed in 293 cell cultures, infection with vir al isolates obtained from primary Kaposi's sarcoma lesions induced inj ury in 293 cells typical of herpesvirus infection and was associated w ith apoptotic cell death. Interestingly, transient overexpression of t he Kaposi's sarcoma-associated herpesvirus v-Bcl-2 homolog delayed the process: of apoptosis and prolonged the survival of infected 293 cell s. In contrast, the broad-spectrum caspase inhibitors Z-VAD-fmk and Z- DEVD-fmk failed to protect infected cell cultures, suggesting that Kap osi's sarcoma-associated herpesvirus-induced apoptosis occurs through a Bcl-2-dependent pathway. Kaposi's sarcoma-associated herpesvirus iso lates from primary Kaposi's sarcoma lesions and body cavity-based lymp homas therefore may differ and are likely to have distinct contributio ns to the pathophysiology of Kaposi's sarcoma.