Central nervous system infection following vertical transmission of Coxsackievirus B4 in mice

Abstract

Coxsackie B viruses (CV-B) are important pathogens associated with several central nervous system (CNS) disorders. CV-B are mainly transmitted by the faecal-oral route, but there is also evidence for vertical transmission. The outcome of in utero CV-B infections on offspring's CNS is poorly explored. The aim of this study was to investigate vertical transmission of CV-B to the CNS. For this purpose, pregnant Swiss albino mice were intraperitoneally inoculated with CV-B4 E2 at gestational days 10G or 17G. Different CNS compartments were collected and analyzed for virus infection and histopathological changes. Using plaque assays, we demonstrated CV-B4 E2 vertical transmission to offspring's CNS. Viral RNA persisted in the CNS up to 60 days after birth, as evidenced by a sensitive semi-nested(sn) reverse transcripton(RT)-PCR method. This was despite infectious particles becoming undetectable at later time points. Persistence was associated with inflammatory lesions, lymphocyte infiltration and viral dsRNA detected by immunohistochemistry. Offspring born to dams mock- or virus-infected at day 17G were challenged by the same virus at day 21 after birth (-+ and ++ groups, respectively). Sn-RT-PCR and histology results compared between both ++ and -+ groups, show that in utero infection did not enhance CNS infection during challenge of the offspring with the same virus.

Assessment of Thymic Output Dynamics After in utero Infection of Mice With Coxsackievirus B4

“…In this study, thymic function was explored in pregnant Swiss albino (an outbred strain which more accurately reflects natural variations inside a population) mice that were orally inoculated by CV-B4 E2 at two different time points. As previously explained (33), the CV-B4 E2 strain that we used was isolated by Yoon et al (34) but shares 99% homology with the E2 plaque-purified variant of the CV-B4 Edwards strain already isolated by Kibrick and Benirschke (35) from the myocardial tissue of a neonate who suffered from encephalohepatomyocarditis (with focal necrosis and inflammation of the pancreas) and died 36 h after birth. The virus was vertically transmitted from mother to the infant based on serological and virological evidence.…”