Pancreas of coxsackievirus-infected dams and their challenged pups: A complex issue

Authors

Sona Sarmirova, Slovak Medical University
Maria Borsanyiova, Slovak Medical University
Brigita Benkoova, Slovak Medical University
Michaela Pospisilova, Slovak Medical University
Rajkumar Rajasekaran, University of Nebraska-LincolnFollow
Katarina Berakova, Martinske biopticke centrum s.r.o
Pavol Gomolcak, Cytopathos, s.r.o
Jay Reddy, University of Nebraska - LincolnFollow
Shubhada Bopegamage, Slovak Medical UniversityFollow

ORCID IDs

0000-0002-8423-5565

Document Type

Article

Date of this Version

2019

Citation

VIRULENCE 2019, VOL. 10, NO. 1, 207–221

Comments

© 2019 The Author(s).

Open access

https://doi.org/10.1080/21505594.2019.1589364

Abstract

Enteroviral infections are frequent, often asymptomatic in humans and during gravidity. The present study is an extension of our previous investigations where we had shown pancreatitis in challenged pups of CVB4-E2-infected dams. Present investigation describes the effect of gestational infection with this virus on the pancreas of both dams and their challenged pups. Gravid CD1 outbred mice were orally infected with CVB4-E2 virus at different gestation times. Pups were challenged orally with the same virus after 25 days of birth. Organs were collected at selected intervals postinfection (p.i.), and replicating virus and viral-RNA copies were analyzed. Additional readouts included histopathology and immunohistochemical (IHC) analysis for localization and identification of Ly6G+ cells (neutrophils), CD11b+ cells (macrophages), and viral protein in pancreatic tissue sections of the infected dams and their challenged pups. Our results show the presence of replicating virus in the pancreas of infected dams and their challenged pups, with inflammation leading to chronic necrotizing pancreatitis and atrophy of pancreatic acini of the dams and their offspring. IHC analysis of the infiltrating cells showed pronounced Ly6G+ neutrophils in dams only, whereas CD11b+ macrophages were present in tissues of both, the pups and the dams. Time of infection during gravidity as well as the p.i. intervals when mice were sacrificed influenced the pancreatic pathophysiology in both groups. We conclude that coxsackievirus infection during pregnancy is a risk factor for chronic affliction of the exocrine tissue and could affect endocrine pancreas in the mother and child.