Strains of coxsackie virus B4 differed in their ability to induce acute pancreatitis and the responses were negatively correlated to glucose tolerance

Hindersson, Maria; Örn, Anders; Harris, Robert A.; Frisk, Gun

doi:10.1007/s00705-004-0347-2

Cited by 11 publications

(11 citation statements)

References 53 publications

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“…Of these cases, a substantial proportion is thought to be the result of a viral infection, and in particular coxsackievirus B4 has been frequently associated with viral‐induced pancreatitis 28, 29. Infection of mice with CVB4 results in a severe acute pancreatitis that is characterized by oedema, acinar cell necrosis, steatonecrosis and infiltration of several immune cells, including lymphocytes, macrophages and neutrophils 2, 9, 30, 31. However, the exact mechanisms responsible for the extensive exocrine tissue damage following CVB4 infection remain poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory rather than infectious insults play a role in exocrine tissue damage in a mouse model for coxsackievirus B4‐induced pancreatitis

Palma

Thibaut

et al. 2009

The Journal of Pathology

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Infection with coxsackievirus B4 (CVB4) may result in an acute severe necrotizing pancreatitis that mostly remains restricted to the acini of the exocrine parenchyma. The mechanisms responsible for this tissue damage, however, remain poorly understood. We here report that COAM, a polyanionic carboxylic acid, provides marked protection against CVB4-induced pancreatitis in a mouse model. Despite the fact that COAM largely reduced disease severity, as detected by serum amylase and lipase levels as well as histologically, titres of replicating CVB4 in the pancreas were virtually unaffected. COAM treatment diminished the infection-associated MMP-9 levels and also resulted in a decreased influx of neutrophils into the infected pancreas. Moreover, we demonstrate that titres of replicating virus in the pancreas did not directly correlate with the severity of disease. In conclusion, our data suggest that immunopathological effects, rather than direct virus-induced destruction, are responsible for the damage to acinar tissue in CVB4-induced pancreatitis.

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Section: Discussionmentioning

confidence: 99%

Inflammatory rather than infectious insults play a role in exocrine tissue damage in a mouse model for coxsackievirus B4‐induced pancreatitis

Palma

Thibaut

et al. 2009

The Journal of Pathology

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“…However, most Coxsackie B viruses are cytolytic, and infection with such a virus would not be in agreement with the clinical picture of type 1A diabetes. The ability of the VD2921 strain to induce diabetes in CBA/j mice has been tested [Hindersson et al, 2001] and, even though the blood sugar values were normal, the result of a glucose tolerance test at 14 and 115 dpi showed that the glucose clearance was hampered significantly in these mice compared with mice infected with the E2 strain and with controls.…”

Section: Discussionmentioning

confidence: 99%

Complete nucleotide sequence of a Coxsackievirus B‐4 strain capable of establishing persistent infection in human pancreatic islet cells: Effects on insulin release, proinsulin synthesis, and cell morphology

Yin

Berg

Westman

et al. 2002

Journal of Medical Virology

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The aim of the present investigation was to study the effect of infection of human pancreatic islet cells with a strain (VD2921) of Coxsackie B virus serotype 4 capable of establishing persistent infection in these cells, as well as to sequence the strain, to study the determinants of virulence and persistence. Groups of islets were infected and assessments of proinsulin, insulin content, and virus replication were made. Insulin release in response to high glucose was measured. Infected and control islets displayed a strong insulin response to high glucose 3-4 days as well as 7-8 days post-infection (dpi). At 11-17 dpi, the infected islets did not respond at all to high glucose, and the response of the control islets was at this late time point somewhat reduced. The insulin and proinsulin content of the infected islets did not differ significantly from that of the control islets. TCID(50) titrations showed that the VD2921 strain replicated in the islet cells during the whole study. Electron microscopic examination of infected islets did not reveal any virus-induced changes of cell morphology compared with the controls, although higher magnifications of the infected beta-cells showed virus-like particles in the cytoplasm. These results show that certain strains of Coxsackievirus B-4 in vitro can establish a persistent infection that might mimic, the more gradual loss of beta-cell function seen during the clinical course of autoimmune diabetes. The ability of this Coxsackievirus B-4 strain to establish a persistent infection might be due to substitution of 11 amino acids located at the surface of the structural protein VP1, adjacent to the predicted receptor binding canyon of the virus.

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“…To evaluate viral replication, inflammation and glucose tolerance, infection with three CV‐B4 strains (E2, V89 4557 and VD2921) and with one CV‐B3 strain (Nancy) was performed in CBS/j mice [15]. A glucose tolerance test, performed at several time‐points post‐infection, showed that both in control mice and infected mice with CV‐E2 and CV‐B3 there was normal glucose absorption from the blood.…”

Section: Studies In Animal Modelsmentioning

confidence: 99%

Immunology in the clinic review series; focus on type 1 diabetes and viruses: how viral infections modulate beta cell function

Grieco

Sebastiani

Spagnuolo

et al. 2012

Clinical and Experimental Immunology

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SummaryType 1 diabetes mellitus (T1DM) is a multi-factorial immune-mediated disease characterized by the autoimmune destruction of insulin-producing pancreatic islet beta cells in genetically susceptible individuals. Epidemiological evidence has also documented the constant rise in the incidence of T1DM worldwide, with viral infections representing one of the candidate environmental risk factors identified by several independent studies. In fact, epidemiological data showed that T1DM incidence increases after epidemics due to enteroviruses and that enteroviral RNA can be detected in the blood of >50% of T1DM patients at the time of disease onset. Furthermore, both in-vitro and ex-vivo studies have shown that viruses can infect pancreatic beta cells with consequent effects ranging from functional damage to cell death.

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Strains of coxsackie virus B4 differed in their ability to induce acute pancreatitis and the responses were negatively correlated to glucose tolerance

Cited by 11 publications

References 53 publications

Inflammatory rather than infectious insults play a role in exocrine tissue damage in a mouse model for coxsackievirus B4‐induced pancreatitis

Inflammatory rather than infectious insults play a role in exocrine tissue damage in a mouse model for coxsackievirus B4‐induced pancreatitis

Complete nucleotide sequence of a Coxsackievirus B‐4 strain capable of establishing persistent infection in human pancreatic islet cells: Effects on insulin release, proinsulin synthesis, and cell morphology

Immunology in the clinic review series; focus on type 1 diabetes and viruses: how viral infections modulate beta cell function

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