Patterns of Gene Expression and a Transactivation Function Exhibited by the vGCR (ORF74) Chemokine Receptor Protein of Kaposi's Sarcoma-Associated Herpesvirus

Abstract

The ORF74 or vGCR gene encoded by Kaposi's sarcoma-associated herpesvirus (KSHV; also called human herpesvirus 8) has properties of a ligand-independent membrane receptor signaling protein with angiogenic properties that is predicted to play a key role in the biology of the virus. We have examined the expression of vGCR mRNA and protein in primary effusion lymphoma (

Remodeling of VE-cadherin junctions by the human herpes virus 8 G-protein coupled receptor

“…Morphological studies have shown that most of the cells in KS lesions are latently infected, whereas a low fraction of cells from unknown origin appear to contain replicative virus (Orenstein et al, 1997;Grundhoff and Ganem, 2004). Of note, vGPCR is also expressed in a small subset of cells in KS (5-10%) (Chiou et al, 2002). Importantly, pharmacological depletion of vGPCRexpressing cells in mice results in global changes throughout the KS-like tumor mass (Montaner et al, 2006) suggesting it significantly contributes to KS development and progression.…”

“…Although the non-KS lesion was negative for vGPCR mRNA, in contrast, all six KS analyzed were positive for vGPCR gene expression (Figure 5c). Even if the proportion of vGPCR-expressing cells cannot be determined here, this number is expected to be low as previously reported (Chiou et al, 2002). We then prepared whole protein lysates from skin KS biopsies to determine whether the vGPCR signaling pathway observed in vitro could be operational in human KS.…”

The pleiotropic effects of Kaposi's sarcoma herpesvirus

“…A small proportion -in most studies less than 3% -of KSHV-infected cells express viral proteins characteristic of productive viral replication [62,72,73]. KS lesions contain mostly circular episomal genomes, again indicative of latency, but a small component of linear genomes, reflecting productive viral replication, can be seen in some biopsies [74].…”

“…As illustrated in Figure 2 and summarized schematically in Figure 1, a small proportion, in most cases less than 3%, of KS spindle cells express viral proteins characteristic of the viral lytic replication cycle [62,72,73]. Viral proteins found to be expressed in rare cells of KS lesions include PF-8 (orf 59) and RTA (orf 50) [62,72,73,111,112].…”

“…Viral proteins found to be expressed in rare cells of KS lesions include PF-8 (orf 59) and RTA (orf 50) [62,72,73,111,112]. The expression of the viral interleukin 6 homologue (vIL-6) was found to be highly variable [62,113].…”