NEW MICROBIOLOGICA, 36, 257-265, 2013 Latent Herpesvirus 8 infection improves both insulin and glucose uptake in primary endothelial cells Angela Ingianni, Enrica Piras, Samuela Laconi, Fabrizio Angius, Barbara Batetta, Raffaello Pompei Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy INTRODUCTION Human Herpesvirus 8 (HHV8) has a characteris- tic tropism for B lymphocytes and is known as the causative agent of the Kaposi sarcoma (KS), as well as of some B cell lymphoproliferative dis- eases, namely primary effusion lymphoma (PEL) and multicentric Castleman disease (reviewed by Ablashi et al., 2002; Hengge et al., 2002; Dourmishev et al., 2003; Ganem, 2010; Wen and Damania, 2010). KS lesions are characterized by neoangiogenesis and the production of typical spindle cells of en- dothelial origin. In vitro HHV8 infection of en- dothelial cells causes dramatic changes in the cel- lular phenotype resembling the spindle shape of KS lesion cells (Ablashi et al., 2002). On the oth- er hand, the effects of lytic and latent HHV8 in- Corresponding author Dr. Raffaello Pompei Microbiology Section, University of Cagliari Via Porcell, 4 - 09124 Cagliari, Italy E-mail: rpompei@unica.it fection on endothelial cell functions and trigger- ing of inflammatory processes are still largely un- known (Caselli et al., 2007; Gregory et al., 2012). HHV8 infection induces profound modifications in the behaviour of both primary and immortali- zed endothelial cells. HHV8 causes an intense transcriptional repro- gramming in HUVEC cells (Wang et al., 2004), stimulates the Warburg effect in latently infected TIME endothelial cells with an increase in gly- colysis and glucose consumption (Delgado et al., 2010) and activates hypoxia-induced factors (Carroll et al., 2006). In a recent work, Rose et al. (2007) found that in HHV8-infected dermal mi- crovascular cells (E-DMVEC) the expression of the insulin receptor (IR) was strongly induced in latently infected cells. Binding of ligands to the IR triggered a signal cascade that led to a similar activation of downstream effector molecules, which regulated cell growth and survival (Ottensmeyer et al., 2000; Raggo et al., 2005; McAllister & Moses, 2007). Over-expression of the IR in KS tissue compared to normal skin was reported by Wang et al. (2004) Human Herpesvirus 8 (HHV8), the causative agent of Kaposi sarcoma, induces a profound modification of infected cell behaviour, with reprogramming of gene expression and changes in physiological properties, over-expression of the insulin receptor, increased resistance to stress conditions and prolonged cell survival in conditions of serum dep- rivation. This paper shows that HHV8 infection induces a strong enhancement of both insulin and glucose uptake in primary endothelial cells (HUVEC). The increase in insulin uptake is already evident in the lytic phase of the viral infectious cycle, and reaches a maximum of up to 71% during the latent phase, whilst glucose uptake is slightly depressed dur- ing the lytic viral infection, but significantly enhanced compared with the control during the latent phase of viral in- fection, with an average increase of about 37% 25 days after cell infection. KEY WORDS: Cell-host interaction, Latent viral infection, Cell metabolism, Insulin uptake. SUMMARY Received December 6, 2012 Accepted March 23, 2013