Outcome of challenge with coxsackievirus B4 in young mice after maternal infection with the same virus during gestation

Abstract

Enteroviral infections go usually unnoticed, even during pregnancy, yet some case histories and mouse experiments indicate that these viruses may be transmitted vertically. More frequently, however, transmission occurs by (fecal) contamination during and shortly after birth. The aim of this study was to investigate the effect of maternal infection in mice (1) on gravidity outcome and (2) on subsequent challenge of the offspring with the same virus. CD1 outbred female mice were infected by the oral route with coxsackievirus B4 strain E2 or mock-infected at days 4, 10, or 17 of gestation. Weight and signs of sickness were noted daily. Pups were infected at day 25 after birth (4 days postweaning). Organs (brain, pancreas, and heart) were analyzed for viral RNA and histopathology. We observed that maternal infection at day 4 or day 17 of gestation had little effect on pregnancy outcome, whereas infection at day 10 affected dams and/or offspring. Infection of pups resulted in severe inflammation of the pancreas, but only when dams were previously infected, especially at day 17. The blood glucose levels were elevated. Because no trace of infection was found at the time of challenge, a role for immunopathology is suggested.

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

“…The results are consistent with our previous work on oral infection with the CVB3-Nancy strain and CVB4-JVB [16,17], and with the CVB4-E2-infected pups of uninfected mothers [18]. However, our observations differ from the published in vivo data obtained with outbred CD1 mice and CVB4-E2 [1,6,10], which showed induction of pancreatitis, hyperglycemia and inflammation of beta cells.…”

“…from the previous study [18] was the absence of islet infiltration despite pancreatitis, but unlike the NOD.SCID mice, the latter showed hyperglycemia, suggesting the necessity of the second insult for affliction of the islet function without infiltration in the islets.…”

“…Similarly, the peripancreatic soft fat tissue inflammation observed in the pancreas of all CVB4-E2-infected mice in the early phase of infection seems to be a peculiarity of oral-CVB4-E2-mouse-models, because such observations were absent in our oral CVB3 mouse models but present in the pancreas of the CVB4-E2 orally infected (-/?) pups [16][17][18]. Pancreas of NOD.SCID mice, which lack the Tand B-cell response, also showed pancreatic adipose tissue inflammation suggesting that the infiltrating cells consisted of macrophages, NK cells, the APC/dendritic cells and polymorphonuclear granulocytes.…”

“…Considering our previous studies [17,18] and the published literature, we selected mouse strains with genetically different backgrounds: 1) outbred (Swiss albino and CD1), 2) inbred (SJL, non-obese diabetic [NOD]), and 3) transgenic (NOD.SCID). Virus stocks were prepared in green monkey kidney (GMK) cells (from the Public Health Authority, Prague).…”

Immunoglobulin G-dependent enhancement of the infection with Coxsackievirus B4 in a murine system

“…15,17,18,19,9 Moreover it has been shown that in adult mice homologous challenge with CVB4-E2 resulted in hyperglycaemia, 20 and that challenge of pups of dams infected during pregnancy resulted in enhanced pathology in the offspring through possibly immune-mediated mechanisms due to pre-existing immunity. 21 In conclusion, in vitro assays displayed that serum samples of mice inoculated with CV-B4 E2 had an enhancing effect able to increase, on the one hand, the CV-B4 E2-induced production of antiviral mediators by spleen cells cultures and, on the other hand, the infection of these cells with CV-B4 E2. This enhancing effect was due to IgG present in CV-B4 E2-infected mice sera but not in those from mock-infected animals, which strongly suggests that anti-CV-B4 E2 antibodies were involved in the process.…”