KSHV SEQUENCES IN BIOPSIES AND CULTURED SPINDLE CELLS OF EPIDEMIC, IATROGENIC AND MEDITERRANEAN FORMS OF KAPOSIS-SARCOMA

The pathogenesis of Kaposi's sarcoma (KS) is still unclear, and severa l factors appear to be involved in the onset of the Kaposi's lesion. E pidemiological studies suggest that a common infective agent may contr ibute to KS. Sequences which appear to represent a new gammaherpesviru s, currently termed KSHV/HHV8, have recently been identified in KS. To further examine the relationship between this virus and KS, we obtain ed biopsy samples of KS lesions; these samples, the spindle cells cult ured from these lesions and the PBMC of the same patients were tested for the presence of KSHV sequences by PCR. In addition, we tested seve ral ''late passage'' KS spindle cell lines as well as control samples. The biopsy samples were from lesions of the following forms of KS: on e sporadic KS, two epidemic KS and three iatrogenic KS, one of which w as in the process of regressing after reduction of immunosuppressive t herapy, and two that were at different stages (patch and nodular) from a single patient. The sporadic KS specimen was positive, as were the PBMCs from this patient, and cells grown from this biopsy appeared to contain KSHV viral sequences up to the fifth passage. Both epidemic KS biopsies were positive, but in these cases KSHV sequences were not de tected in the cultured cells. The biopsy from the regressing iatrogeni c KS lesion was negative, as were the cells cultured from this lesion. However, the PBMCs of this patient were weakly positive for KSHV at t he time of biopsy, and PBMCs collected from this patient one month lat er were completely negative. The samples of both the patch and the nod ular KS lesions obtained from another immunosuppressed patient showed amplifiable sequences of KSHV, but both the PBMCs of this patient and primary KS cell cultures from these biopsies were negative. Of the lat e-passage KS lines tested, only one, IST AIDS KS 12, was positive for KSHV. This line is derived from an early angiomatous-macula lesion. Ta ken together, these data suggest that an active KSHV infection is asso ciated with KS and that elimination of KSHV from the lesion precedes r egression of the lesion, strongly correlating KSHV with KS. In additio n, early KS lesions may have a higher KSHV burden, or contain cells mo re susceptible to KSHV infection, further linking KSHV to KS.