Effects of cyclosporine and hydrocortisone on Kaposi's sarcoma-associated herpesvirus genome replication and cell apoptosis induction.

BACKGROUND: Iatrogenic immunosuppressed patients are at increased risk for development of various cancers that comprise Kaposi's sarcoma (KS). METHODS: To investigate the direct impact of immunosuppressive agents on Kaposi's sarcoma-associated herpesvirus (KSHV) and KS development, we quantified the effects of cyclosporine (CsA) and hydrocortisone (HC) on KSHV genome replication and the consequences on the cell survival. RESULTS: In the presence of phorbol ester 12-O-tetradecanoyl phorbol-13-acetate, we observed an increase of intracellular and extracellular KSHV DNA concomitantly with an increase of gp (glycoprotein) K8.1 expression, indicating KSHV genome replication. This replication was accompanied by cell apoptosis. In comparison, in the presence of CsA, HC, or both, we did not observe any effect on KSHV replication or gp K8.1 expression. CONCLUSION: Our results suggest that immunosuppressive agents such as HC and CsA do not activate the lytic cycle of KSHV and do not modify the cell survival thus promoting cancer progression by a direct cellular effect.

Human herpesvirus-8 seroconversions after renal transplantation.

BACKGROUND: Human herpesvirus-8 (HHV-8) is a new human herpesvirus that is clearly associated with Kaposi's sarcoma (KS). A previous study has reported that the prevalence of KS in a cohort of renal transplant recipients with previous HHV-8 infection was 28% and two other studies have shown that KS can be linked to HHV-8 seroconversion after graft. The aim of this study was to evaluate the HHV-8 seroconversion rate in a cohort of renal allograft recipients in Paris. METHODS: Two hundred eighty-seven patients who were HHV-8 seronegative before renal transplantation were tested for HHV-8 antibodies by an immunofluorescence assay 12 months after transplantation. RESULTS: Of the 287 patients, 6 (2.09%) seroconverted after renal transplantation. None of these 6 patients developed KS within 3 years of the first HHV-8 positive serum. None of the clinical manifestations that could be associated with HHV-8 primary infection were observed during the seroconversion. CONCLUSIONS: Our results demonstrated that HHV-8 seroconversion can be observed even in a low HHV-8 prevalence area and confirmed the need to perform systematic screening for HHV-8 antibodies in renal graft donors and recipients.