Abstract 3478: Latent KSHV infection increases the vascular permeability of endothelial cells

Abstract

Abstract Infection with Kaposi's sarcoma-associated herpesvirus (KSHV) is closely linked to the development of Kaposi's sarcoma (KS). The KS lesion is driven by KSHV-infected endothelial cells and is highly dependent on autocrine and paracrine factors for survival and growth. We report that latent KSHV infection increases the vascular permeability of endothelial cells. Latent KSHV-infected endothelial cells display increased Src kinase activity, increased Rac1 activation and activation of its downstream modulator, p21 activated kinase (PAK1). The KSHV-infected endothelial cells exhibited increases in tyrosine phosphorylation of VE-cadherin and β-catenin, while total levels of these proteins remained unchanged, suggesting that latent infection disrupted endothelial cell junctions. Consistent with these findings, we found that latent KSHV-infected endothelial cells were more permeable than uninfected endothelial cells. Knockdown of Rac1, as well as inhibition of ROS, resulted in decreased permeability of the KSHV-infected endothelial cells. In sum, KSHV latent infection increases the vascular permeability of infected endothelial cells thereby contributing to the pathogenesis of Kaposi's sarcoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3478. doi:10.1158/1538-7445.AM2011-3478