Human antibodies isolated from plasma by affinity chromatography increase the coxsackievirus B4-induced synthesis of interferon-alpha by human peripheral blood mononuclear cells in vitro.
Coxsackievirus B4 (CVB4) can be found in circulating blood of patients; however, the interaction of CVB4 with peripheral blood mononuclear cells (PBMCs) is poorly understood. CVB4 induced low levels of IFN-alpha synthesis in PBMCs from healthy donors. In contrast, preincubation of infectious CVB4 with plasma from these donors containing anti-CVB4 antibodies strongly enhanced the synthesis of IFN-alpha. IgG obtained from plasma by chromatography formed immune complexes with CVB4 and increased significantly the CVB4-induced production of IFN-alpha by PBMCs. These antibodies did not have a neutralizing effect on CVB4 infection of Hep-2 cells. The role of CVB and adenovirus receptor (CAR), FcgammaRII and FcgammaRIII in the increased synthesis of IFN-alpha induced by CVB4 preincubated with IgG was shown by inhibition with specific antibodies. The major interferon-alpha-producing cells in response to CVB4-IgG complexes were CD14(+) cells and monocyte-enriched PBMCs. With the latter, detection of IFN-alpha by immunostaining was positive whereas in monocyte-depleted PBMCs it was not. This study shows that CVB4-induced synthesis of IFN-alpha by PBMCs can be enhanced by an antibody-dependent mechanism through interactions between the virus, non-neutralizing antivirus antibodies, FcgammaRII and III and CAR.
Chehadeh
Wassim
W
Laboratoire de Virologie, Centre Hospitalier Régional et Universitaire, Institut Gernez-Rieux, 59037 Lille Cedex, France1.
Bouzidi
Ahmed
A
SEDAC Therapeutics, IBL-CNRS, 59021 Lille, France2.
Alm
Gunar
G
Department of Veterinary Immunology, Biomedical Center, Uppsala, Sweden3.
Wattré
Pierre
P
Laboratoire de Virologie, Centre Hospitalier Régional et Universitaire, Institut Gernez-Rieux, 59037 Lille Cedex, France1.
Hober
Didier
D
Laboratoire de Virologie, Centre Hospitalier Régional et Universitaire, Institut Gernez-Rieux, 59037 Lille Cedex, France1.
D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000302:isolation & purification / Q000494:pharmacology*; D002648:Child; D002846:Chromatography, Affinity; D003384:Coxsackievirus Infections / Q000097:blood / Q000276:immunology*; D004770:Enterovirus / Q000276:immunology*; D005260:Female; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007074:Immunoglobulin G / Q000494:pharmacology; D016898:Interferon-alpha / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008297:Male; D008875:Middle Aged
D000914:Antibodies, Viral; D007106:Immune Sera; D007074:Immunoglobulin G; D016898:Interferon-alpha