Coxsackie B4 viruses with the potential to damage Beta cells of the islets are present in clinical isolates

Abstract

Infections with Coxsackie viruses (especially Coxsackie B4) are thought to be involved in the pathogenesis of diabetes. Many interdependent variables determine the outcome of an infection with a Coxsackie virus, one of them being the tropism of the virus for a specific tissue. The extent to which Beta cell tropic variants of Coxsackie B4 virus occur naturally was assessed. Human isolates of this virus were tested in an in vitro system in which elevated insulin release from infected islets incubated at a non-stimulatory (2 mmol/l) glucose concentration appears to be related to viral attack. Using this technique, 8/24 isolates tested, impaired secretory function in mouse islets. Some strains of Coxsackie B4 virus, therefore, will directly infect mouse islets in vitro leading to changes in islet cell function. In conclusion, these findings confirm that variants of Coxsackie B4 virus with the potential to damage Beta cells occur quite frequently in the natural population. In certain circumstances the damage they inflict on Beta cells may cause destruction of these cells, or precipitate overt diabetes.

Molecular Analysis of an Echovirus 3 Strain Isolated from an Individual Concurrently with Appearance of Islet Cell and IA-2 Autoantibodies

“…In addition, there is no established mouse model for echovirus 3. The use of human islet cells is complicated by the observation that all enteroviruses seem to infect these cells, causing a wide range of alterations (apoptosis, necrosis, or changes in insulin secretion without clear damage), and which of these correlate with diabetogenicity is not clear (7,41,42,49,54). Thus, a range of models and additional enterovirus strains isolated during prospective studies and at the time of onset are required to further address the role of enteroviruses in T1D.…”

Environmental Triggers and Determinants of Type 1 Diabetes

“…It has been proposed that pancreatic ␤-cell tropic variants of the coxsackie B virus are present in the general population and that they are able to induce ␤-cell damage in susceptible individuals (48). The biological significance of enterovirus tropism has been demonstrated by the highly specific nature of the motorneuron damage in poliomyelitis, and it is possible that viral tropism could also explain the specificity of ␤-cell damage in type 1 diabetes.…”

Persistent Infection of Human Pancreatic Islets by Coxsackievirus B Is Associated with Alpha Interferon Synthesis in β Cells

“…It has been shown that variants of CVB circulating in the natural population are tropic for the mouse ␤ cells (45). The prototype CVB4, which had been serially passaged through mouse pancreas and then mouse ␤ cells, could replicate in mouse islets and was able to damage ␤ cells in vitro and to induce IDDM in vivo (46).…”