The Kaposi’s sarcoma-associated herpesvirus E3 ubiquitin ligase K5 acts as a novel oncogene, altering cellular metabolism and signaling: implications for tumorigenesis MEETING ABSTRACTS Open Access The Kaposi’s sarcoma-associated herpesvirus E3 ubiquitin ligase K5 acts as a novel oncogene, altering cellular metabolism and signaling: implications for tumorigenesis Roshan Karki, Sabine M Lang, Robert E Means* From 12th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies (ICMAOI) Bethesda, MD, USA. 26-27 April, 2010 While it is clear that Kaposi’s sarcoma-associated her- pesvirus (KSHV or HHV-8) is the causative agent of a number of malignancies including multicentric Castle- man’s disease, primary effusion lymphoma, and Kaposi’s sarcoma (KS), the molecular mechanisms of tumor induction by this virus are still unclear. In part, KS lesion presentation is thought to be driven primarily through paracrine mechanisms and is mainly observed in immunocompromised patients. Monocyte subsets, including dendritic cells and macrophages, are crucial to immune system functionality and are also skewed in KS patients. The goals of this study were to investigate a potential role for the E3 ubiquitin ligase K5 of KSHV, which plays a role in viral immune evasion, in altering monocyte functionality, thereby contributing to KSHV- driven tumorigenesis. A series of wild-type (WT) and mutant K5-expressing stable cell lines were generated in THP-1 monocytic cell line and examined. Surprisingly, these cells demon- strated a serum-dependent increased growth rate and a propensity to acidify the growth medium as compared to vector-THP-1 cells. Biochemical examination indi- cated that K5 induced aerobic glycolysis and other hall- marks of the “Warburg Effect,” including increased lactate production and glucose uptake. Observed increases in Akt and total cellular tyrosine phosphoryla- tion, combined with the serum-dependence, suggested a role for receptor tyrosine kinases (RTKs).