Anti-Human Herpesvirus 8 antibodies affect both insulin and glucose uptake by virus-infected human endothelial cells.

INTRODUCTION: Human Herpesvirus 8 (HHV8) is known to be the cause of the malignant tumour named Kaposi's sarcoma. It is believed to induce an intense modification of cell metabolism in endothelial cells. In this work we analysed the role of anti-HHV8 antibodies in both the insulin and glucose uptake of HHV8-infected primary human endothelial cells (HUVEC). METHODOLOGY: Western blotting, immunofluorescence and radiolabelled glucose were employed to assess the pPI3K expression, insulin binding and glucose-uptake by HUVEC cells, respectively. RESULTS: We confirmed that HHV8-infection is able to enhance both insulin binding and glucose-uptake in HHV8-infected primary endothelial cells; in addition, we found that anti-HHV8 specific antibodies are able to further increase both insulin and glucose uptake during the late latent phase of HHV8-infection in vitro. CONCLUSIONS: These findings suggest that a specific immune response to HHV8-infection may cooperate in boosting the cell metabolism, further enhancing the already increased insulin binding and glucose-uptake in HHV8-infected cells, which is a peculiar property of several oncogenic viruses.

High Prevalence of Human Herpesvirus 8 Infection in Diabetes Type 2 Patients and Detection of a New Virus Subtype.

The prevalence of Human Herpesvirus 8 (HHV8) DNA and antiviral antibodies in Diabetes type 2 (DM2) and control subjects was studied, in order to confirm a possible link between DM2 and HHV8 infection. The HHV8-DNA from diabetic patients was typed for detecting possible genomic differences with known HHV8 reference viruses.DM2 patients and healthy controls were examined for the presence of HHV8 DNA into the peripheral blood lymphocytes. Both anti-lytic and latent phase antibodies were detected in HHV8 positive and negative diabetic patients, as well in a number of controls. The HHV8 ORF K1 and ORF 26 genes from DM2 patients were typed and matched to reference strains.A significant prevalence of HHV8 DNA in DM2 subjects versus healthy controls was detected (about 58 % against 27 %). Anti-lytic phase, but not anti-latent phase antibodies, were significantly increased in DM2 patients versus controls. In addition, about 30 % of HHV8 strains isolated from DM2 lymphocytes showed consistent differences in the ORF 26 gene sequence, so that a new HHV8 subtype was proposed. These findings give additional support to the hypothesis that HHV8 could be considered an additional risk factor for DM2 onset.

High prevalence of HHV8 infection and specific killer cell immunoglobulin-like receptors allotypes in Sardinian patients with type 2 diabetes mellitus.

The development of type 2 diabetes is thought to involve both environmental, possibly infectious, and genetic factors. Recently, a high prevalence of human herpesvirus 8 (HHV8) infection was observed in type 2 diabetes patients, and specific killer cell immunoglobulin-like receptors (KIR) allotypes were associated to both increased susceptibility to herpesvirus infection and risk to develop diabetes. However, no clear gene-disease or virus-disease associations have been established. To investigate the possible interplay between HHV8 infection, KIR allotype and type 2 diabetes, virus prevalence and KIR genotype were analyzed by PCR in 168 patients affected by type 2 diabetes and 108 control individuals belonging to the Sardinian population. Results showed a significant increase of HHV8 prevalence in type 2 diabetes patients versus controls (57% vs. 17%, P < 0.001), and a significant increase of KIR2DL2/DS2 homozygosity in diabetes patients infected with HHV8 compared to uninfected ones (64% vs. 14%, P < 0.0001), resulting in a significant OR of 11.31. In addition, the analysis of the frequency of the KIR2DL2/DS2 receptor and its HLA-C1 ligand, accordingly to the status of HHV8 infection, showed a significant increased correlation between KIR2DL2/DS2, type 2 diabetes and HLA-C1C1 genotype in the type 2 diabetes patients infected with HHV8 compared to uninfected ones (62% vs. 15%, P < 0.0001, OR = 8.64). These findings provide preliminary evidence that HHV8 infection might be a cofactor for type 2 diabetes in a specific subset of genetically susceptible individuals, and suggest the possibility that such patients might have an impaired immune-mediated component contributing to the development of type 2 diabetes.