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.


CONCLUSIONS
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.
Marcelin
A G
AG
Department of Virology, CERVI, Pitié-Salpêtrière Hospital, AP-HP, 83 Bd de l'Hôpital, 75013 Paris, France.
Milliancourt
C
C
Dupin
N
N
Wirden
M
M
Huraux
J M
JM
Agut
H
H
Calvez
V
V
D017209:Apoptosis / Q000187:drug effects*; D016572:Cyclosporine / Q000009:adverse effects*; D004261:DNA Replication / Q000187:drug effects*; D019288:Herpesvirus 8, Human / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D006854:Hydrocortisone / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016133:Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014764:Viral Proteins / Q000032:analysis; D014779:Virus Replication / Q000187:drug effects*
D007166:Immunosuppressive Agents; D014764:Viral Proteins; D016572:Cyclosporine; D013755:Tetradecanoylphorbol Acetate; D006854:Hydrocortisone