Minimal reactivation of Kaposi's sarcoma-associated herpesvirus by corticosteroids in latently infected B cell lines.
Corticosteroid use in transplant recipients increases the incidence and severity of Kaposi's sarcoma (KS), a disease associated with KS-associated herpesvirus (KSHV) infection. Recently, the prototypic corticosteroid, hydrocortisone, was shown to directly induce lytic cycle reactivation of KSHV in latently-infected BCBL-1 cells. The purpose of this study was to examine this phenomenon in further detail. After incubation with dexamethasone (<or= 30 microM) or hydrocortisone (<or= 30 microM) for 1-4 days, we evaluated KSHV reactivation in latently infected B cell lines (BC-1, BC-3, and BCBL-1) by assessing early-lytic PF-8 and late-lytic gpK8.1 protein expression using flow cytometry. Viral particle production was monitored by quantifying KSHV minor capsid protein levels in cell culture supernatants. A small increase in the percentage of cells expressing viral lytic proteins was observed in BCBL-1, but not in the other cell lines. In combination with 3 nM 12-O-tetradecanoyl-phorbol-13-acetate, a known chemical inducer of KSHV replication, corticosteroids (0.3 microM) enhanced KSHV reactivation twofold in some cell lines, but not in others. In all experiments, lytic viral protein expression by flow cytometry correlated with production of viral particles in culture supernatants. In summary, we found that corticosteroids were limited inducers of KSHV reactivation in latently infected cells. Thus, our findings suggest that corticosteroids do not enhance the incidence and severity of KS in transplant recipients by direct cellular effects on KSHV reactivation.
Zoeteweij
J Paul
JP
Dermatology Branch, National Cancer Institute, Bethesda, Maryland 20892-1908, USA.
Rinderknecht
Andrea S
AS
Davis
David A
DA
Yarchoan
Robert
R
Blauvelt
Andrew
A
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology / Q000821:virology; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006023:Glycoproteins / Q000096:biosynthesis; D019288:Herpesvirus 8, Human / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D012514:Sarcoma, Kaposi / Q000821:virology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014764:Viral Proteins / Q000096:biosynthesis; D014775:Virus Activation; D017735:Virus Latency / Q000187:drug effects*
D000305:Adrenal Cortex Hormones; D005938:Glucocorticoids; D006023:Glycoproteins; C113454:K8.1 protein, Human herpesvirus 8; C110348:ORF59 protein, Human herpesvirus 8; D014764:Viral Proteins; D003907:Dexamethasone; D013755:Tetradecanoylphorbol Acetate; D006854:Hydrocortisone