Viral protein VP4 is a target of human antibodies enhancing coxsackievirus B4- and B3-induced synthesis of alpha interferon.
Coxsackievirus B4 (CVB4)-induced production of alpha interferon (IFN-alpha) by peripheral blood mononuclear cells (PBMC) is enhanced in vitro by nonneutralizing anti-CVB4 antibodies from healthy subjects and, to a higher extent, from patients with insulin-dependent diabetes mellitus. In this study, we focused on identification of the viral target of these antibodies in CVB systems. High levels of IFN-alpha were obtained in supernatants of PBMC incubated with CVB4E2 or CVB3 and plasma from healthy subjects and, to a higher extent, from patients. The VP4 capsid proteins dissociated by heating at 56 degrees C from CVB4E2 (VP4(CVB4)) and CVB3 (VP4(CVB3)) but not H antigen preincubated with plasma from healthy subjects or patients inhibited the plasma-dependent enhancement of CVB4E2- and CVB3-induced IFN-alpha synthesis. There was no cross-reaction between VP4(CVB4) and VP4(CVB3) in the inhibiting effect. IFN-alpha levels in culture supernatants showed dose-dependent correlation with anti-VP4 antibodies eluted from plasma specimens using VP4-coated plates. There were higher index values for anti-VP4 antibodies detected by enzyme-linked immunosorbent assay (ELISA) and higher proportions of positive detection in 40 patients than in 40 healthy subjects (80% versus 15% for anti-VP4(CVB4)). There was no relationship between the levels of anti-CVB neutralizing antibodies and the detection of anti-VP4 antibodies by ELISA. The CVB plasma-induced IFN-alpha levels obtained in PBMC cultures in the anti-VP4 antibody-positive groups were significantly higher than those obtained in the anti-VP4 antibody-negative groups regardless of the titers of anti-CVB neutralizing antibodies. These results show that VP4 is the target of antibodies involved in the plasma-dependent enhancement of CVB4E2- and CVB3-induced IFN-alpha synthesis by PBMC.
Chehadeh
Wassim
W
Service de Virologie/ UPRES EA3610, Faculté de Médecine, Université Lille 2, Bâtiment Paul Boulanger, CHRU Lille, 59037 Lille, France.
Lobert
Pierre-Emmanuel
PE
Sauter
Pierre
P
Goffard
Anne
A
Lucas
Bernadette
B
Weill
Jacques
J
Vantyghem
Marie-Christine
MC
Alm
Gunnar
G
Pigny
Pascal
P
Hober
Didier
D
D000328:Adult; D000914:Antibodies, Viral / Q000276:immunology*; D036022:Capsid Proteins / Q000276:immunology*; D002648:Child; D003429:Cross Reactions; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D029822:Enterovirus B, Human / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000821:virology; D012016:Reference Values
D000914:Antibodies, Viral; D036022:Capsid Proteins; D016898:Interferon-alpha