Identification and functional characterization of a spliced rhesus rhadinovirus gene with homology to the K15 gene of Kaposi's sarcoma-associated herpesvirus

Abstract

Rhesus monkey rhadinovirus (RRV) is a gamma-2 herpesvirus related to the human Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8). This study identified an alternatively spliced gene at the right side of the RRV genome (strain 17577) between open reading frame 75 and the terminal repeat region. Of its eight exons, the first seven encoded up to 12 transmembrane domains, whilst the eighth exon encoded a predicted C-terminal cytoplasmic domain. Structurally and positionally, this RRV gene therefore resembles the K15 gene of KSHV; it was provisionally named RK15 to avoid confusion with other RRV17577 genes. In ectopic expression studies, the 55 kDa RK15 protein isoform activated the JNK and NF-kB pathways, like the 45 kDa KSHV K15-encoded protein isoform. In contrast to K15, which activates angiogenic and inflammatory cytokines such as interleukin (IL)-8, IL-6 and CCL20, the range of cellular transcripts activated by the RRV K15 homologue was much more restricted, but included IL-6, IL-8 and FGF21. These data suggest functional differences between terminal membrane proteins at the right end of the genomes of Old World primate gamma-2 herpesviruses.

Kaposi's Sarcoma Herpesvirus K15 Protein Contributes to Virus-Induced Angiogenesis by Recruiting PLCγ1 and Activating NFAT1-dependent RCAN1 Expression

“…We have shown earlier that K15, through its cytoplasmic C terminal domain activates the NFκB pathway [52], [58], [60] and that this involves the NFκB component RelA/p65 (unpublished). To investigate the involvement of the NFκB pathway in K15-induced capillary tube formation, we silenced RelA/p65 using siRNA.…”

Inhibiting the Recruitment of PLCγ1 to Kaposi’s Sarcoma Herpesvirus K15 Protein Reduces the Invasiveness and Angiogenesis of Infected Endothelial Cells

“…Previous studies reported that both K15 alleles activate NF-κB and the Ras/MAPK signalling [ 22 – 25 ]. Microarray studies revealed that K15 upregulates the expression of genes involved in angiogenesis and cell migration [ 22 , 24 , 25 ], including, among others, COX2 and an NFAT-dependent upregulation of DSCR1 [ 17 , 24 , 25 ]. We previously showed that K15 contributes to the increased angiogenic properties of KSHV infected primary endothelial cells in a matrigel-based capillary tube formation assay [ 17 ].…”

Use of Transgenic Parasites and Host Reporters To Dissect Events That Promote Interleukin-12 Production during Toxoplasmosis

“…Although the injection of rhoptry proteins without productive invasion by the parasite (kiss-and-run model) could account for these populations, it was also possible that in vivo these cells were activated by IFN-␥ to destroy intracellular parasites (46,47), giving rise to a subpopulation of cells with a U-I phenotype due to injection of the Cre during invasion and subsequent death of the parasite. To address this possibility, Ai6 mice were treated with control rat IgG antibody or anti-IFN-␥ monoclonal antibody and infected with Pru-Cre-mCherry.…”