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

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.

Murine experimental models for studying the pathogenesis of coxsackieviruses

“…Also, our unpublished data show that the wild type strain of CVB2-Ohio does not induce any changes in the endocrine and exocrine pancreas but mild inflammation in the heart. Our studies (Bopegamage et al, 2012;Sarmirova et al, 2019) on the effect of gestational infection by CVB4-E2 on the pancreas of both dams and their challenged pups showed that the replicating virus was present in the pancreas of infected dams and their challenged pups. We also observed presence of inflammation leading to chronic necrotizing pancreatitis and atrophy of the acinar tissue of the dams and their offspring.…”

“…These studies show that it is important to know the background of the mice. The autoimmune aspects of coxsackievirus infection have been reviewed by Rose (2008).…”

Coxsackievirus B3 Infection of Human iPSC Lines and Derived Primary Germ-Layer Cells Regarding Receptor Expression

“…Moreover, within the missed abortion group 5 cases were demonstrated to be CVB3-positive [ 3 ]. In a mouse model of CVB4-E2 infection during pregnancy, dams were infected at different time points during gravidity starting at embryonic day (E) 4 [ 58 ]. E4 is the time point of blastocyst implantation in the mouse [ 59 ].…”

Engineering organ-on-a-chip systems to model viral infections

“…Human enteroviruses can be transmitted through oral routes, causing different illnesses, which can be serious. For example, coxsackievirus B (CVB) enterovirus, which can induce multi-organ disease, including pancreas and liver [17,[42][43][44][45], requires the use of appropriate in vitro models for its study. The use of conventional models does not allow us to reproduce the physical complexity of the human intestinal mucosa containing different cell types and properties, which include absorptive, mucus-secreting, enteroendocrine, Paneth cells and villus structures by using a static cell culture [46,47].…”