Enterovirus Infection of Cultured Human Pancreatic Islets
The factors involved in viral tropism for pancreatic islets and islet response to infection can be studied in an experimental model utilizing pancreatic islets isolated from organ donors and cultivated as free-floating preparations. Enteroviruses, in general, have a tropism for human pancreatic islets in vitro. Both lytic and persistent enterovirus infections have been characterized under different experimental conditions and viruses have been detected in both insulin-producing and non-insulin-producing cells. Delayed (secondary) necrosis after initial pyknosis is the major mechanism of cell death during lytic enterovirus infection in cultured human pancreatic islets, whereas apoptosis appears to play only a minor role. Pancreatic beta-cell tropism and the ability to induce beta-cell dysfunction and death probably depends both on the genetic properties of the virus and on the host cell response to the infection. Viral properties are likely to affect the phenomenon since some enterovirus strains are highly cytolytic whereas others show progeny production with no apparent islet destruction in vitro. Even for highly destructive virus strains, there is a significant delay between viral progeny production and pancreatic islet destruction in vitro, suggesting a role for secondary, virus-induced, host factors in the process.
KeywordsMigration Recombination Interferon Insulinoma
This work is supported by grants from the European Union (EP7-HEALTH-2007, DIAPREPP N202013), the Juvenile Diabetes Research Foundation (USA), The Academy of Finland, and Päivikki and Sakari Sohlberg Foundation.
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