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

ABSTRACT

It was demonstrated that specific IgG can enhance the infection with CV-B4, in vitro, in the human system. This enhancement could be involved in the pathophysiology of CV-B4 induced diseases. To investigate further the role of enhancing IgG in the infection with CV-B4 E2 in vivo, animal models are needed. Therefore, it was decided to assess whether inoculation of CV-B4 E2 to mice results in the appearance of IgG able to enhance the infection with this virus. Swiss albino mice were inoculated with CV-B4 E2 intraperitoneally. Serum samples were obtained from tail vein blood collected from day 0 to day 80 p.i. IgG were isolated by Protein G affinity chromatography. Seroneutralisation assays were carried out. In total murine spleen cells cultures inoculated with CV-B4 E2 mixed with various dilutions of serum or IgG samples, the enhancing activity was assayed through i) the antiviral activity titer of supernatants ii) the detection of intracellular viral RNA by RT-PCR iii) the level of infectious particles in supernatants.

In most serum samples (76/105), neutralizing and enhancing activities were detected peaking between days 14 and 30 p.i and were higher in sera from mice inoculated with 2.10⁶ TCID50 units than with lower doses. The enhancing activity was due to the IgG-enriched fraction of serum from CV-B4 E2 infected animals but not from control animals.

These data show that IgG from immune mice can enhance the infection of splenocytes with CV-B4 E2 in vitro and open the way to explore whether such an enhancing activity can play a role in vivo.

KEYWORDS:

• antiviral activity
• enteroviral RNA
• enterovirus
• in vitro
• serum
• spleen cells

This article is referred to by:

Enterovirus infections: Pivoting role of the adaptive immune response

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Funding

This study was supported by: the Comité Mixte de Coopération Universitaire Franco-Tunisien (CMCU 08/G808) and Egide Paris. Ministère de l'Enseignement Supérieur et de la Recherche Scientifique, (LR99ES27), Tunisia, Ministère de l'Education Nationale de la Recherche et de la Technologie, Université Lille 2 (Equipe d'Accueil 3610), France, and Center Hospitalier Régional et Universitaire de Lille, and EU FP7 (GA-261441-PEVNET: Persistent virus infection as a cause of pathogenic inflammation in type 1 diabetes - an innovative research program of biobanks and expertise).