In vivo growth-restricted and reversible malignancy induced by Human Herpesvirus-8/ KSHV: a cell and animal model of virally induced Kaposi's sarcoma

Transfection of a Kaposi's sarcoma (KS) herpesvirus (KSHV) Bacterial Artificial Chromosome (KSHVBac36) into mouse bone marrow endothelial lineage cells generates a cell (mECK36) that forms KS-like tumors in mice. mECK36 expressed most KSHV genes and were angiogenic, but didn't form colonies in soft agar. In nude mice, mECK36 formed KSHV-harboring vascularized spindle-cell sarcomas that were LANA+/podoplanin+, overexpressed VEGF and Angiopoietin ligands and receptors, and displayed KSHV and host transcriptomes reminiscent of KS. mECK36 that lost the KSHV episome reverted to non-tumorigenicity. siRNA suppression of KSHV vGPCR, an angiogenic gene up-regulated in mECK36 tumors, inhibited angiogenicity and tumorigenicity. These results show that KSHV malignancy is in vivo growth- restricted and reversible, defining mECK36 as a biologically sensitive animal model of KSHV-dependent KS.