Antibody‐Dependent Enhancement of Coxsackievirus B4 Infectivity of Human Peripheral Blood Mononuclear Cells Results in Increased Interferon‐α Synthesis

Hober, Didier; Chehadeh, Wassim; Bouzidi, Ahmed; Wattré, P

doi:10.1086/323801

Cited by 63 publications

(66 citation statements)

References 34 publications

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“…Based on this hypothesis, the anti-CV-B4 enhancing activity in serum of human beings previously described by our team could be considered as a risk factor for enhanced pathology in case of exposure to CV-B4. 9,10,11 Similarly an enhancing activity toward any CV-B would be a risk factor for enhanced pathology in case of homologous, and possibly, heterologous challenge with CV-B. Interestingly, in patients with type 1 diabetes, an anti-CV-B4 enhancing activity of serum was observed.…”

Section: Discussionmentioning

confidence: 97%

“…Interestingly, in patients with type 1 diabetes, an anti-CV-B4 enhancing activity of serum was observed. 11,26,27 Whether enhancing antibodies play a role in the pathogenesis of CV-B -induced diseases in vivo, especially type 1diabetes deserves further studies. Future studies will be directed along this line in our laboratory.…”

Section: Discussionmentioning

confidence: 99%

“…2,6,7,8 It has been shown that non-neutralizing anti-CV-B4 IgG obtained from serum of patients can increase the infection of peripheral blood mononuclear cells (PBMC) with CV-B4, which results in production of IFNa and other inflammatory cytokines. 9,10,11,12,13,14 The role of enhancing IgG levels in the outcome of CVB4 infections and other conditions such type 1 diabetes, cannot be ignored. 12,14 However the impact of anti-CV-B4 enhancing activity of serum/IgG in the infection with this virus, in vivo, remains to be investigated.…”

Section: Introductionmentioning

confidence: 99%

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Anti-coxsackievirus B4 (CV-B4) enhancing activity of serum associated with increased viral load and pathology in mice reinfected with CV-B4

et al. 2016

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In previous studies it was shown that inoculation of Swiss albino mice with CV-B4 E2 resulted in the production of serum IgG capable of enhancing the CV-B4 E2 infection of murine spleen cells cultures. To investigate whether such an enhancing activity of serum can play a role in vivo, we decided to study the CV-B4 E2 infection in mice exposed to successive inoculations of virus. In Swiss albino mice infected with CV-B4 E2 at the age of 21 days, anti-CV-B4 E2 neutralizing and enhancing activities of their serum peaked after 55 d. In contrast, mice inoculated at the age of 55 d expressed much lower activities. Despite the neutralizing activity of serum, CV-B4 E2 inoculated a second time to 55 day-old animals spread into the host. At the age of 72 and 89 d the levels of viral RNA and infectious particles were higher in organs of animals exposed to 2 successive infections compared with animals infected once at the age of 21 d or 55 d. In animals with 2 successive inoculations of CV-B4 E2 there was a relationship between the anti-CV-B4 E2 enhancing activity of serum and the level of viral RNA in organs and an enhancement of pathology was observed as displayed by histological analysis of pancreas and hyperglycaemia. Altogether our data strongly suggest that an anti-CV-B4 E2 enhancing activity in the host can play a role in the outcome of a secondary infection with this virus.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Anti-coxsackievirus B4 (CV-B4) enhancing activity of serum associated with increased viral load and pathology in mice reinfected with CV-B4

et al. 2016

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“…This pattern of data is in agreement with previous reports of the serum/IgGdependent enhancement of the infection of human PBMC with CV-B4 E2, which was due to non-neutralizing antibodies bound to viral particles. 8,9,14 In the human system it was shown that the target cells of serum/IgG-dependent enhanced CV-B4 E2 infection among PBMC were monocytes. 7,8 Further studies are needed to identify which cell types are infected through enhancing serum/IgG within mouse spleen cells cultures in order to determine whether macrophages are involved since these cells can be reservoirs for viruses within lymphoid organs with implications in the pathogenesis of CV-B4 E2 -induced diseases.…”

Section: Discussionmentioning

confidence: 99%

“…6,7 That increase was the consequence of an enhancement of the infection of PBMC with CV-B4 E2 by non-neutralizing anti-CV-B4 E2 IgG. 8,9 The role of the anti-CV-B4 E2 enhancing activity of serum in the outcome of the infection by this virus, in vivo, remains to be determined.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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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 2.10 6 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.

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Enhancing and neutralizing anti‐coxsackievirus activities in serum samples from patients prior to development of type 1 diabetes

Sané¹,

Bertin²,

Sioofy‐Khojine

et al. 2020

Diabetes Metabolism Res

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Background Studies in prospective cohorts have suggested that enterovirus infections are associated with the appearance of islet autoantibodies that precede later appearance of type 1 diabetes (T1D). It was shown that in addition to an antibody‐mediated anti‐coxsackievirus (CV)‐B neutralizing activity of serum from patients with T1D, there was also enhancing anti‐CV‐B activity in vitro. In this study, the patterns of enhancing and neutralizing anti‐CV activities were analysed from consecutive serum samples collected from children who were followed from birth until they developed T1D in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study and compared to those in non‐diabetic control children. Methods The titres of serum neutralizing activity were analysed against those CVs which were detected in the stools in these children (CV‐B3, CV‐B5 or CV‐A4) using plaque assay. The enhancing activity of these serum samples was analysed by measuring interferon‐alpha (INF‐α) production in cultures of peripheral blood mononuclear cells (PBMC) inoculated with a mixture of these viruses and diluted serum. Results A sustained anti‐CV enhancing activity was observed in consecutive serum samples in patients with T1D. The pattern of responses differed between children who developed T1D and control children. In patients, the anti‐CV enhancing activity was predominant or even exclusive over the neutralizing activity, whereas in controls the enhancing and neutralising activities were more balanced or the neutralizing activity was largely predominant. Conclusions Evaluating the anti‐enterovirus neutralizing and enhancing activity of serum samples can be useful to investigate further the relationship between enteroviruses and the development of T1D.

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Antibody‐Dependent Enhancement of Coxsackievirus B4 Infectivity of Human Peripheral Blood Mononuclear Cells Results in Increased Interferon‐α Synthesis

Cited by 63 publications

References 34 publications

Anti-coxsackievirus B4 (CV-B4) enhancing activity of serum associated with increased viral load and pathology in mice reinfected with CV-B4

Anti-coxsackievirus B4 (CV-B4) enhancing activity of serum associated with increased viral load and pathology in mice reinfected with CV-B4

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

Enhancing and neutralizing anti‐coxsackievirus activities in serum samples from patients prior to development of type 1 diabetes

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