KSHV-mediated ROS induction defines novel therapeutic targets in Kaposi's sarcoma

Abstract

Background Kaposi’s sarcoma herpesvirus (KSHV) is the etiological agent of Kaposi’s sarcoma (KS). Understanding the interplay of viral and host factors in KS carcinogenesis is critical for the rational development of new therapies. Reactive oxygen species (ROS) have a recognized broad function in oncogenesis mediated by signaling cascades leading to the Rac1 activation of NADPH oxidases (Nox) [1]. ROS play a role in cell cycle regulation and angiogenesis, yet the specific molecular events linking ROS and these cancer hallmarks are still elusive. KSHV encodes a constitutively active G protein-coupled receptor (vGPCR) [2], which triggers KS-like sarcomagenesis via Rac1 [3]. It has been shown that Rac1-activated mutant induces tumors resembling Kaposi’s sarcoma by a ROS-mediated mechanism in transgenic mice [4,5]. Moreover, Rac1 is overexpressed in AIDS-KS lesions and in KSHV-infected mECK36 tumors, pointing to a role for KSHV-induced Rac1-mediated production of ROS in KS pathogenesis [5]. The current study explored the induction of oxidative stress pathways in the KSHVinduced mouse model mECK36.