The Human HerpesVirus 8 infection alters lipid synthesis and induces neutral lipid accumulation in primary endothelial cells

POMPEI, RAFFAELLO;Sabrina UDA;Enrica PIRAS;Fabrizio ANGIUS;Barbara BATETTA;INGIANNI, ANGELA

2013-01-01

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Abstract

Human Herpes Virus 8 (HHV8), the causative agent of Kaposi’s sarcoma (KS), induces an intense transcriptional reprogramming of endothelial (HUVEC) cells in vitro, prolonging their life span and augmenting cell survival in the presence of apoptotic inducers. In this work, lipid synthesis and metabolism were studied inHHV8infectedHUVECcells. Cholesterol and triglyceride synthesis were analysed by the use of 14C acetate and 14C oleate during lytic and latent HHV8 infection from days +3 to +24. A quantitative analysis of neutral lipids in infected cells was performedin situ using Nile Red dye, which displayed a red emission for polar lipids and a yellowemission for neutral lipids. The results showed that during the lytic phase (1 4 days after HHV8 infection) a depression of cholesterol and cholesterol ester synthesis (about 26%) was observed, while triglycerides appeared to be enhanced up to 45% as compared to controls. After 14 24 days, during the latent phase of infection, there was an increased synthesis of cholesterol (up to +44%) and cholesterol esters (up to +58%) in infected cells, whereas triglycerides were progressively lowered. Imaging analysis showed that the lipid droplets and total neutral lipid content were definitely higher (up to +85%) in HHV8 infected cells compared to the controls. Lipid synthesis inhibitors Sigma C75 and Sandoz 58035 were used to examine the importance of lipid synthesis modification and neutral lipid accumulation in the pathogenesis of KS and neo angiogenesis. This work was financed by the Fondazione Banco di Sardegna 2012.