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

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.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

Coxsackievirus-B4E2 can infect monocytes and macrophages in vitro and in vivo

International audienceViral RNA (vRNA) is found in mice inoculated with coxsackievirus-B4E2 (CV-B4E2). The CV-B4E2 infection of murine spleen cells in vitro is enhanced with CV-B4E2-infected mouse serum. It has been investigated whether monocyte/macrophages were targets of CV-B4E2 in mice. vRNA has been detected in spleen and bone marrow of infected animals. The levels of vRNA were higher in CD14 + cells than in CD14- spleen cells and in F4/80- cells than in F4/80 + spleen cells. Meanwhile, CD14 + cells and F4/80- cells were more permissive to CV-B4E2 in vitro and the infection was enhanced when the virus was mixed with immune serum. While CV-B4E2 infected BMDM cultures (98% F4/80 +); however, the immune serum did not enhance the infection. In conclusion, CV-B4E2 infects monocytes (CD14 +, F4/80-) and macrophages (CD14 +, F4/80 +) in vivo and immune serum can enhance the in vitro infection of these cells arising out of the spleen

In-utero coxsackievirus B4 infection of the mouse thymus

Type B coxsackievirus (CV-B) infections are involved frequently in the triggering of several autoimmune diseases such as myocarditis, dilated cardiomyopathy, pericarditis, pancreatitis, type 1 diabetes, encephalitis, thyroiditis or Sjo€gren’s syndrome. Serological and virological evidence suggests that maternal infections during pregnancy can play a role in the appearance of these diseases in offspring. The current study aims to explore the effect of an in-utero CV-B infection on the fetal thymus, the central site for programming immunological self-tolerance. In this perspective, female Swiss albino mice were inoculated intraperitoneally or orally with the diabetogenic CV-B4 E2 strain at gestational days 10 or 17. Offspring were killed at different post-inoculation times, and their thymuses were analysed for evidence of infection and alterations in thymic T cell subsets. In-utero CV-B infection of the thymus was demonstrated during the course of vertical transmission, as attested by viral RNA and infectious virus detection in most analysed samples. No histopathological changes were evident. Thymic T cells were not depleted, despite being positive for viral RNA. As evidenced by flow cytometry analysis, CV-B infection of the fetal thymus induced significant changes of thymic T cell populations, particularly with maternal inoculation at gestational day 10. Altogether, these findings suggest that CV-B infection of the fetal thymus may play an important role in the genesis of autoimmune diseases