J. Chang et al., Inflammatory cytokines and the reactivation of Kaposi's sarcoma-associatedherpesvirus lyric replication, VIROLOGY, 266(1), 2000, pp. 17-25
Kaposi's sarcoma (KS) is a complex proliferative lesion long suspected of b
eing dependent on exogenous paracrine signaling molecules to stimulate its
proliferative, angiogenic, and inflammatory components. In particular, both
clinical and experimental observations have pointed to a potential role fo
r inflammatory cytokines as permissive factors for KS development, but KS p
athogenesis is also critically dependent on infection by an exogenous herpe
svirus, the KS-associated herpesvirus (KSHV). To examine the possible links
between inflammatory cytokines and KSHV replication, we tested for the abi
lity of such cytokines to induce lytic viral reactivation in the latently i
nfected BCBL-1 cell line. lnterferon-gamma consistently activated KSHV repl
ication, whereas tumor necrosis factor, interleukin-1, interleukin-2, inter
leukin-6, granulocyte-macrophage colony stimulating factor, and basic fibro
blast growth factor did not. Glucocorticoids also failed to induce lytic KS
HV growth in these cells, bur: ionomycin, a calcium ionophore, induced repl
ication and strongly augmented the known inductive effects of phorbol ester
s. Interferon-alpha had a dose-dependent inhibitory effect on KSHV inductio
n by ionomycin. The identification of interferon-gamma as an activator and
interferon-alpha as an inhibitor of KSHV induction in vitro correlates well
with in vivo observations and demonstrates for the first time that inflamm
atory cytokines can directly modulate KSHV replication. (C) 2000 Academic P
ress.