KSHV RTA abolishes NFκB responsive gene expression during lytic reactivation by targeting vFLIP for degradation via the proteasome.

ABSTRACT: Kaposi's sarcoma herpesvirus (KSHV) is a gamma-2 herpesvirus present in all cases of Kaposi's sarcoma, primary effusion lymphoma (PEL), and some cases of multicentric Castleman's disease. Viral FLICE inhibitory protein (vFLIP) is a latently expressed gene that has been shown to be essential for survival of latently infected PEL cells by activating the NFκB pathway. Inhibitors of either vFLIP expression or the NFĸB pathway result in enhanced lytic reactivation and apoptosis. We have observed a decrease in vFLIP protein levels and of NFκB activation in the presence of the KSHV lytic switch protein RTA. Whereas vFLIP alone induced expression of the NFĸB responsive genes ICAM1 and TNFα, inclusion of RTA decreased vFLIP induced ICAM1 and TNFα expression in both co-transfected 293T cells and in

SUBMITTER: Ehrlich ES 

PROVIDER: S-EPMC3948842 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature