The Role of Human Herpesvirus 8 in Diabetes Mellitus Type 2: State of the Art and a Medical Hypothesis

Abstract

Diabetes is a common chronic disease due to an altered glucose metabolism, caused by the quantitative and/or qualitative dysfunction of the insulin hormone. Two types of diabetes are recognized: juvenile diabetes, or type 1, which has an autoimmune origin, and adult diabetes, or type 2 (DMT2), which covers 90-95 % of all diabetic patients.The causes of DMT2 are not yet clear: heredity, life style, nutrition, and environment are considered the main risk factors. Several viral infections, namely cytomegalovirus, coxsackie and other enteroviruses, rubella and hepatitis C virus, have been claimed to be associated with some forms of diabetes. The direct role of viruses as a cause or as a risk of type 1 diabetes has been amply described in several recent reviews. Therefore, this review focuses attention on the role of a human herpes pathogenic virus in the onset of DMT2. By carrying out an analysis of recent literature, we describe the findings reported on an extremely deceitful virus, such as Human Herpes virus 8, and present a medical hypothesis on a possible relationship between this virus and DMT2.

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].…”

“…The findings that HHV8 latency is characterized by persistent modifications in endothelial cell metabolism have led some authors to hypothesize a possible involvement of HHV8 infection in the development of a diffused chronic human disease such as DMT2 [65,75,[78][79][80][81][82]. Although KS is considered a rare disease, HHV8 infection has been found to have a high prevalence in some countries, namely in the Mediterranean and African regions [81][82][83].…”

“…Besides the recognized risk factors such as genetics, nutrition, familiarity and environment, increasing evidence indicates that persistent microbial and viral infections may also cooperate in the development of chronic diseases like diabetes. To the best of our knowledge, to date, only HCV and HHV8 viruses have been associated to DMT2 on a biological and epidemiological basis [25,60,61,65,76,78,79,82,87,88]. In particular, HCV has been reported as causing diabetes by its direct action on liver metabolism and also by the activation of a specific immune response that may cause tissue damage, whereas a strong epidemiological association with HHV8 has been described in the last decade [65,75,78,81,82,86].…”

“…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].…”

General and Ophthalmic Manifestations of Herpes Virus Infections

“…Кроме того, не все пациенты с СД II типа инфицированы ВГЧ-8. Поэтому авторы делают вывод о необходимости дальнейшего изучения вопроса о роли различных вирусов в патогенезе СД II типа [50].…”