biostudies-literaturePati SNCI NIH HHS8660-73https://www.ebi.ac.uk/biostudies/studies/S-EPMC115111biostudies-literatureUnknown75(18)Infection with human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma (KS)-associated herpesvirus, is necessary for the development of KS. The HHV-8 lytic-phase gene ORF74 is related to G protein-coupled receptors, particularly interleukin-8 (IL-8) receptors. ORF74 activates the inositol phosphate/phospholipase C pathway and the downstream mitogen-activated protein kinases, JNK/SAPK and p38. We show here that ORF74 also activates NF-kappaB independent of ligand when expressed in KS-derived HHV-8-negative endothelial cells or primary vascular endothelial cells. NF-kappaB activation was enhanced by the chemokine GROalpha, but not by IL-8. Mutation of Val to Asp in the ORF74 second cytoplasmic loop did not affect ligand-independent signaling activity, but it greatly increased the responsJournal of virologyActivation of NF-kappaB by the human herpesvirus 8 chemokine receptor ORF74: evidence for a paracrine model of Kaposi's sarcoma pathogenesis.PMC115111R01 CA055293R01 CA55293P01 CA78817Foulke JSFeldman RAGuo HGPati SKim JCavrois MReitz MfalseActivation of NF-kappaB by the human herpesvirus 8 chemokine receptor ORF74: evidence for a paracrine model of Kaposi's sarcoma pathogenesis.Infection with human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma (KS)-associated herpesvirus, is necessary for the development of KS. The HHV-8 lytic-phase gene ORF74 is related to G protein-coupled receptors, particularly interleukin-8 (IL-8) receptors. ORF74 activates the inositol phosphate/phospholipase C pathway and the downstream mitogen-activated protein kinases, JNK/SAPK and p38. We show here that ORF74 also activates NF-kappaB independent of ligand when expressed in KS-derived HHV-8-negative endothelial cells or primary vascular endothelial cells. NF-kappaB activation was enhanced by the chemokine GROalpha, but not by IL-8. Mutation of Val to Asp in the ORF74 second cytoplasmic loop did not affect ligand-independent signaling activity, but it greatly increased the respons2001-01-01T00:00:00Z2001 Sep2025-05-31T23:22:52.795Z2019-03-27T00:17:06ZS-EPMC1151111150721110.1128/jvi.75.18.8660-8673.2001