title: Pathophysiology of the pancreas after oral infection of genetically diverse mice with coxsackievirus B4-E2.
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.
authors.affiliation: Enterovirus Laboratory, Faculty of Medicine, Slovak Medical University, Limbova 12, 83303, Bratislava, Slovak Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Precechtelova
authors.forename: Maria
authors.initials: M
authors.lastname: Borsanyiova
authors.forename: Darina
authors.initials: D
authors.lastname: Stipalova
authors.forename: Sona
authors.initials: S
authors.lastname: Sarmirova
authors.forename: Pavol
authors.initials: P
authors.lastname: Gomolcak
authors.forename: Katarina
authors.initials: K
authors.lastname: Berakova
authors.forename: Shubhada
authors.initials: S
authors.lastname: Bopegamage
mesh_terms: D000818:Animals; D001786:Blood Glucose; D003920:Diabetes Mellitus / Q000821:virology*; D029822:Enterovirus B, Human / Q000145:classification* / Q000472:pathogenicity*; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D007249:Inflammation / Q000378:metabolism; D016898:Interferon-alpha / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D010179:Pancreas / Q000473:pathology*; D012367:RNA, Viral; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology
chemical_list: D001786:Blood Glucose; D016898:Interferon-alpha; D012367:RNA, Viral; D014764:Viral Proteins