Central nervous system infection following vertical transmission of Coxsackievirus B4 in mice
Pathogens and Disease
Oxford University Press (OUP)
Reason for embargo
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.
This work was supported by Ministère de l’Enseignement Supérieur et de la Recherche Scientifique, (LR99ES27), Tunisia, and Ministère de l’Education Nationale de la Recherche et de la Technologie, Université Lille 2 CHRU Lille (UPRES EA3610), France. Financial support for S.J.R has come from the European Commission 7th Framework Programme PEVNET [FP7/2007-2013] under grant agreement number 261441 and a Juvenile Diabetes Research Foundation (JDRF) Career Development Award (5-CDA-2014-221-A-N). Habib JMII was supported by grants from Ministère de l’Enseignement Supérieur et de la Recherche Scientifique.
This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.
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