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Pathophysiology of the pancreas after oral infection of genetically diverse mice with coxsackievirus B4-E2

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Abstract

Coxsackievirus B4 strain E2 (CVB4-E2) and its association with type 1 diabetes (T1D) have been studied in experimental in vitro and in vivo murine models. CVB4-E2, known to be pancreotropic and diabetogenic in nature, is associated with acute pancreatitis in mice but shows differences in the induction of glycemia after intraperitoneal (i.p.) infection. Therefore, the aim of this work was to study the outcome of oral infection with CVB4-E2 in five mouse strains with different genetic backgrounds: two outbred (Swiss albino, CD1), two inbred (SJL, NOD) and one transgenic (NOD.SCID). Survival rates, fasting blood glucose, histopathology, viral titres and persistence were studied in selected organs and stool samples. Viral protein (VP1), proinflammatory cytokines, and interferon alpha (IFN-α) were analyzed by immunohistochemistry. We observed mortality only in infected NOD and NOD.SCID mice, with differing survival rates implying initial innate protection in the NOD.SCID mice and low virus clearance with replicating virus titres in the studied organs and stool up to day 40 post infection (p.i.). Independent of the mouse strain hyperglycemia, proinflammatory cytokines and histopathological changes were absent in the endocrine pancreas of infected mice. Only the pancreata of the dead NOD.SCID mice showed inflammation even in presence of IFN-α. Host-dependent viral RNA persistence was observed in all outbred mice. In conclusion, oral infection with CVB4-E2, despite the known affinity of this strain towards the pancreatic tissue and the presence of replicating virus, conferred total protection to the endocrine pancreas in all mice and failed to induce the proinflammatory cytokines studied by us.

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Acknowledgments

We thank the Norwegian financial support mechanism, Mechanism EEA and Slovak Government—Project SK0082 and project of the Ministry of Health—Project MZSR 2006/13-SZU-08, both received by S.B.

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Authors and Affiliations

  1. Enterovirus Laboratory, Faculty of Medicine, Slovak Medical University, Limbova 12, 83303, Bratislava, Slovak Republic

    Jana Precechtelova, Maria Borsanyiova, Darina Stipalova, Sona Sarmirova & Shubhada Bopegamage

  2. Cytopathos s. r. o., Limbova 5, 83301, Bratislava, Slovakia Republic

    Pavol Gomolcak & Katarina Berakova

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  1. Jana Precechtelova
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  2. Maria Borsanyiova
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Correspondence to Shubhada Bopegamage.

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Precechtelova, J., Borsanyiova, M., Stipalova, D. et al. Pathophysiology of the pancreas after oral infection of genetically diverse mice with coxsackievirus B4-E2. Arch Virol 160, 103–115 (2015). https://doi.org/10.1007/s00705-014-2236-7

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  • DOI: https://doi.org/10.1007/s00705-014-2236-7

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