Diabetes mellitus due to viruses ? some recent developments

Abstract

Many different viruses belonging to several genera have the potential to damage beta cells. The mechanisms they employ are varied, and infection may result in either a direct destruction of islets and rapid insulin deficiency, or in a more gradual loss of functioning islets with the onset of diabetes many years later. Several case histories involving extensive cytolysis of beta cells can be directly linked to viral infection, whilst an example of diabetes occurring many years after viral infection is found in individuals who had a congenital infection with rubella virus. Here, the virus induces an autoimmune reaction against beta cells. Autoimmune phenomena have also been observed in islets following infections with viruses other than rubella, and thus activation of autoimmune mechanisms leading to beta-cell destruction may be a relatively frequent occurrence. Recent evidence shows that picornaviruses are not exclusively lytic, and can induce more subtle, long-term changes in beta cells, which may be important in the aetiology of diabetes. The exact mechanisms involved are not known, but it is clear that several viruses can directly inhibit insulin synthesis and induce the expression of other proteins such as interferons, and the HLA antigens. Strain differences in viruses are important since not all variants are tropic for the beta cells. Several laboratories are in the process of identifying the genetic determinants of tropism and diabetogenicity, especially amongst the Coxsackie B (CB) virus group. The sequence of one such diabetogenic CB4 strain virus has been determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Type 1 diabetes islet associated antibodies in subjects infected by echovirus 16

“…According to our results, echovirus 16 could be involved in an autoimmune induction against beta-cell antigens, due to the fact that the presence of neutralizing antibodies to echovirus 16 was associated with the appearance of or increases in islet-associated antibody concentrations. This suggests that such enterovirus could be capable of inducing the destruction of pancreatic beta cells by releasing self cytoplasmatic antigens, or indirectly generating cytokine production [7,11,14,15,35,36], all of which might trigger Type 1 diabetes of autoimmune origin in subjects with susceptibility genes [8,10,11,15]. In addition, molecular mimicry can also be an explanation for this association [7,11,14,20,35].…”

“…Among such serotypes, CVB4 and CVB5 have most often been connected to the pathogenesis of Type 1 diabetes, although other studies have reported the participation of other enterovirus serotypes, such as coxsackie A and echoviruses (EV4, EV6 and EV9) [11,14,16,17,18,19,33,34]. Echovirus 16 could be another serotype to be included in the list of enteroviruses related to Type 1 diabetes.…”

“…Our group has reported the association between ICA presence and the meningitis epidemic caused by echovirus 4 [11,16,17,18], and we have found metabolic abnormalities during an oral glucose tolerance test (OGTT) in children infected by this virus [14,17,18]. It has been shown that beta cells from mice infected with echovirus 4 (isolated strains from children of the previously mentioned epidemic) produced less insulin and had reduced synthesis of total proteins [14].…”

“…ICA has been detected in non-diabetic subjects infected with different viruses (mumps, rubella and coxsackie B4) [1,14]. An eventual association between enterovirus infections and seroconversion to ICA has been described in a few cases [6,9,10,11,15].…”

“…It has been shown that beta cells from mice infected with echovirus 4 (isolated strains from children of the previously mentioned epidemic) produced less insulin and had reduced synthesis of total proteins [14]. Such changes were related to alterations in their blood glucose concentrations.…”