Reactivation of latent Kaposi′s sarcoma-associated herpesvirus in human umbilical vein endothelial cells by HIV-1-related inflammatory cytokines
Objective To determine whether HIV-1-related inflammatory cytokines can activate lytic cycle replication of Kaposi′s sarcoma-associated herpesvirus(KSHV) in human umbilical vein endothelial cells(HUVEC) and to investigate its potential role in Rta promoter of KSHV involved in reactivation. Methods Using an in vitro model system, we examined the effect of recombinant human cytokines that were similar to that produced by HIV-1-infected T cells on KSHV replication in latently infected HUVEC. KSHV reactivation was analyzed with Northern blot analysis and quantitative PCR for ORF26 mRNA expression, a gene encoding the KSHV minor capsid protein was only activated during reactivation. The results were extended and confirmed using a luciferase reporter construct driven by the KSHV Rta(replication and transcription activator) promoter, the first promoter activated during KSHV replication. Results Recombinant cytokines, such as gamma interferon(IFN-γ), hepatocyte growth factor/scatter factor (HGF/SF), and oncostatin M(OSM) not only induce KSHV lytic cycle replication, but also stimulate Rta promoter activity in latently infected HUVECs. Conclusion HIV-1-related inflammatory cytokines are responsible for the induction of KSHV lytic cycle replication in HUVEC and the induction may be, at least in part, mediated by Rta promoter of KSHV.