Effects on isolated human pancreatic islet cells after infection with strains of enterovirus isolated at clinical presentation of type 1 diabetes
- 作者：Asma Elshebani ; Annika Olsson ; Jan Westman ; Torsten Tuvemo ; Olle Korsgren ; Gun Frisk
- 关键词：Enterovirus ; b2 ; -cells ; Type 1 diabetes
- 刊名：Virus Research
- 出版年：2007
- 期刊代码：92_01681702
- 类别：imm
- 出版时间：March 2007
- 卷：124
- 期：1-2
- 页码：193-203
- 文件大小：1392 K
摘要
Enterovirus (EV) infections have been associated with the pathogenesis of type 1 diabetes (T1D). They may cause b2;-cell destruction either by cytolytic infection of the cells or indirectly by triggering the autoimmune response. Evidence for EV involvement have been presented in several studies, EV-IgM antibodies have been reported in T1D patients, EV-RNA has been found in the blood from T1D patients at onset, and EV have been isolated from newly diagnosed T1D. Our aim was to study infections with EV isolates from newly diagnosed T1D patients in human pancreatic islets in vitro. Two of them (T1 and T2) originated from a mother and her son diagnosed with T1D on the same day, the other two (A and E) were isolated from a pair of twins at the time of diagnosis of T1D in one of them. Isolated human pancreatic islets were infected and viral replication, viability and degree of cytolysis as well as insulin release in response to high glucose were measured. All four EV isolates replicated in the islet cells and virus particles and virus-induced vesicles were seen in the cytoplasm of the b2;-cells. The isolates varied in their ability to induce cytolysis and to cause destruction of the islets and infection with two of the isolates (T1 and A) caused more pronounced destruction of the islets. Infection with the isolate from the healthy twin boy (E) was the least cytolytic. The ability to secrete insulin in response to high glucose was reduced in all infected islets as early as 3 days post infection, before any difference in viability was observed. To conclude, strains of EV isolated from T1D patients at clinical presentation of T1D revealed b2;-cell tropism, and clearly affected the function of the b2;-cell. In addition, the infection caused a clear increase in the number of dead cells.