Human Herpesvirus 8 infection may contribute to oxidative stress in diabetes type 2 patients

Abstract

Objective: To investigate the link between Human Herpesvirus 8 (HHV8) infection and plasma oxidative stress in patients with diabetes mellitus type 2 (DM2). Results: Blood samples collected from DM2 and control subjects were screened for the presence of antibodies against HHV8 and for biomarkers of oxidative stress. We determined the products of radical damage on the plasma lipid fraction, such as malondialdehyde (MDA), fatty acid hydroperoxides (HP) and 7-ketocholesterol (7-keto), the oxidation products of unsaturated fatty acids (UFA) and cholesterol, respectively. The level of plasma antioxidant α-tocopherol (α-toc) was also assessed. Relevant differences were observed in the redox status in DM2 and either HHV8-positive or-negative control subjects. The level of α-toc significantly decreased in both DM2 and HHV8-positive subjects. Levels of MDA, HP and 7-keto were much higher in HHV8-positive and DM2 subjects, indicating that plasma oxidative stress is a common feature in both DM2 and HHV8-infection. In addition, 7-keto was further increased in HHV8-positive DM2 patients. We hypothesized that the HHV8-infection may contribute to the production of ROS, and hence to the oxidative stress closely related to the pathogenesis and development of DM2.

Human Herpesvirus 8 and Host-Cell Interaction: Long-Lasting Physiological Modifications, Inflammation and Related Chronic Diseases

“…Although HHV8 can cause frequent and severe sarcoma or other lympho-proliferating diseases in immune-depressed subjects, it is generally constrained to the latent phase in order to escape adaptive immunity. It has also been reported that HHV8 together with the activation of both humoral and cellular immunity, as well as the induction of cytokines and reactive oxygen species (ROS), induces persistent metabolic modifications in the infected endothelial cells [60,66,[74][75][76][77][78]. Recently, Angius et al [24] corroborated previous evidence [63,65] and also found that the anti-HHV8 immune response can further enhance the uptake of both glucose and insulin in latently infected endothelial cells, strengthening the hypothesis that anti-HHV8 antibodies provide additional support for virus persistence in the host [24].…”

“…Moreover, the dysfunction of endothelial cells has been involved in the pathophysiology of metabolic diseases and DMT2 [90,91], and endothelial dysfunction is believed to contribute to the clinical expression of atherosclerosis and other complications of diabetes [92]. Overall, several findings have led to the hypothesis that HHV8 could be implicated in inducing some metabolic alterations, such as the increase of insulin binding and glucose uptake, which may be the initial event for activating the metabolic syndrome and diabetes [60,77,78,81,82,89,93]. It is commonly accepted that insulin hyper-secretion is considered a triggering cause of diabetes, and the discovery of the causes that are linked to insulin hyper-secretion is fundamental in the design of specific diabetes treatment [94,95].…”

“…Latent viral infections may induce the activation of adaptive immunity with the increased production of cytokines and ROS [60,74,77,87,96]. Furthermore, the production of ROS is often accompanied by glycolysis, and reliance on ROS production is found to cause a reduction in anaerobic metabolism [90,97].…”

“…In actual fact, recent studies have suggested a physiological role of cellular metabolism in vessel sprouting, and endothelial cells are generally dysregulated in pathological conditions and cancer [99]. Very recently, Incani et al [77] corroborated the assumption that DMT2 is associated to plasma oxidative stress [100], and a similar condition has also been reported in HHV8-infected subjects wherein the HHV8-infection, by inducing abnormal ROS production, most probably contributes to causing and/or maintaining a status of oxidative stress [77] and hence tissue damage. As a consequence, plasma lipid oxidation contributes to endothelial cell dysfunction, which characterizes the onset of atherosclerotic plaque and blood vessel disorders [64,74,[101][102][103].…”

“…On the basis of these considerations, some authors have hypothesized a possible association between chronic HHV8 infection and the onset of chronic diseases such as diabetes. The recent studies performed in the Mediterranean and sub-Saharan Regions have given significant evidence of an epidemiological association between HHV8 infection and DMT2 [77,78,86,89]. Furthermore, the upset of both the glucose and lipid metabolism of endothelial cells has been hypothesized as creating the conditions that favour the metabolic syndrome and decrease in insulin efficiency found in diabetes (Figure 1).…”