Pseudorabies virus infection stimulates pancreatic ductal HCO3- secretion

Background. We have previously shown that hypersecretion can be observed during the early phase of experimental oedematic and necrotizing pancreatitis. However, the source and the role of hypersecretion are unknown. Several viruses have been reported to cause acute pancreatitis, but we have no information concerning the effect of viral infection on pancreatic secretion. Our aim in this study was to examine the effect of acute infection caused by a herpesvirus (pseudorabies virus; PRV) on pancreatic ductal secretion.

Methods. Ba-DupGreen (BDG), a genetically modified replicating strain of PRV was used in this study. The green fluorescent protein (GFP) gene was inserted into the PRV antisense promoter region located in the inverted repeat segment of the virus. Small intra/interlobular ducts were isolated from the pancreas of guinea pigs. Ducts were incubated in McCoy's based culture medium containing BDG virus (107 plaque forming units/ml) for 6 hours, while the control ducts were incubated only with the culture media. The ducts were then cultured for further 18 hours. The rate of HCO3- secretion was determined as described earlier (Hegyi et al. Am J Physiol Cell Physiol 285: C268-C276, 2003). All the experiments were performed in HCO3–buffered Ringer solution at 37oC. Viral structural proteins were visualized by immunohistochemistry. Native GFP expression and immunofluorescence signals were recorded by a confocal laser scanning microscope.

Results and Conclusions. The virus infected all accessible epithelial cells of the duct as judged by the appearance of GFP and viral antigens in the ductal cells. PRV infection stimulated ductal HCO3- secretion about 4–5-fold after 24h. We suggest that this response of pancreatic ducts to PRV infection could represent a defence mechanism against invasive pathogens to avoid pancreatic injury.

This work was supported by The Wellcome Trust and OTKA.