Antibody-dependent enhancement and ...
Document type :
Article dans une revue scientifique: Article original
DOI :
PMID :
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Title :
Antibody-dependent enhancement and neutralization against CVB4 investigated in vitro and in silico through an agent-based model.
Author(s) :
Morvan, Corentin [Auteur]
Laboratoire de Virologie - ULR 3610 [Laboratoire de Virologie]
Nekoua, Magloire Pandoua [Auteur]
Laboratoire de Virologie - ULR 3610 [Laboratoire de Virologie]
Debuysschere, Cyril [Auteur]
Laboratoire de Virologie - ULR 3610 [Laboratoire de Virologie]
Alidjinou, Enagnon Kazali [Auteur]
Laboratoire de Virologie - ULR 3610 [Laboratoire de Virologie]
Hober, Didier [Auteur]
Laboratoire de virologie - ULR 3610
Laboratoire de Virologie - ULR 3610 [Laboratoire de Virologie]
Nekoua, Magloire Pandoua [Auteur]
Laboratoire de Virologie - ULR 3610 [Laboratoire de Virologie]
Debuysschere, Cyril [Auteur]
Laboratoire de Virologie - ULR 3610 [Laboratoire de Virologie]
Alidjinou, Enagnon Kazali [Auteur]
Laboratoire de Virologie - ULR 3610 [Laboratoire de Virologie]
Hober, Didier [Auteur]
Laboratoire de virologie - ULR 3610
Journal title :
Journal of Medical Virology
Abbreviated title :
J Med Virol
Volume number :
96
Pages :
e29399
Publication date :
2024-01-20
ISSN :
1096-9071
HAL domain(s) :
Sciences du Vivant [q-bio]/Médecine humaine et pathologie
English abstract : [en]
The infection with coxsackievirus B4 (CVB4) can be enhanced in vitro by antibodies directed against the viral capsid protein VP4. In peripheral blood mononuclear cells, antibody-dependent enhancement (ADE) of CVB4 infection ...
Show more >The infection with coxsackievirus B4 (CVB4) can be enhanced in vitro by antibodies directed against the viral capsid protein VP4. In peripheral blood mononuclear cells, antibody-dependent enhancement (ADE) of CVB4 infection leads to the production of interferon alpha (IFN-α). To investigate ADE of CVB4-induced production of IFN-α, an agent-based model was constructed with enhancing and neutralizing antibodies. The model recapitulates viral neutralization and ADE in silico. The enhancing and neutralizing activities of serum samples were evaluated in vitro to confront the model predictions with experimental results. Increasing the incubation time of CVB4 with serum samples improves virus neutralization in silico as well as in vitro. It also results in ADE at lower antibody numbers in silico, which is confirmed in vitro with IFN-α production at lower serum concentrations. Furthermore, incubation of CVB4 with serum at a low temperature does not induce IFN-α production in vitro. Thus, taken together our results suggest that enhancing antibodies bind cryptic epitopes, more accessible with longer incubation time and at higher temperature due to changes in capsid conformation, consistent with previous results indicating that enhancing antibodies are anti-VP4 antibodies.Show less >
Show more >The infection with coxsackievirus B4 (CVB4) can be enhanced in vitro by antibodies directed against the viral capsid protein VP4. In peripheral blood mononuclear cells, antibody-dependent enhancement (ADE) of CVB4 infection leads to the production of interferon alpha (IFN-α). To investigate ADE of CVB4-induced production of IFN-α, an agent-based model was constructed with enhancing and neutralizing antibodies. The model recapitulates viral neutralization and ADE in silico. The enhancing and neutralizing activities of serum samples were evaluated in vitro to confront the model predictions with experimental results. Increasing the incubation time of CVB4 with serum samples improves virus neutralization in silico as well as in vitro. It also results in ADE at lower antibody numbers in silico, which is confirmed in vitro with IFN-α production at lower serum concentrations. Furthermore, incubation of CVB4 with serum at a low temperature does not induce IFN-α production in vitro. Thus, taken together our results suggest that enhancing antibodies bind cryptic epitopes, more accessible with longer incubation time and at higher temperature due to changes in capsid conformation, consistent with previous results indicating that enhancing antibodies are anti-VP4 antibodies.Show less >
Language :
Anglais
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
Université de Lille
CHU Lille
CHU Lille
Collections :
Submission date :
2024-02-02T22:02:44Z
2024-02-13T11:56:10Z
2024-02-13T11:56:10Z