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Journal of Virology, November 2005, p. 13882-13891, Vol. 79, No. 22
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.22.13882-13891.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Viral Protein VP4 Is a Target of Human Antibodies Enhancing Coxsackievirus B4- and B3-Induced Synthesis of Alpha Interferon

Wassim Chehadeh,^1, Pierre-Emmanuel Lobert,¹ Pierre Sauter,¹ Anne Goffard,¹ Bernadette Lucas,¹ Jacques Weill,² Marie-Christine Vantyghem,³ Gunnar Alm,⁴ Pascal Pigny,⁵ and Didier Hober^1*

Service de Virologie/UPRES EA3610, Faculté de Médecine-Université Lille 2, Bâtiment Paul Boulanger, CHRU Lille, 59037 Lille,¹ Unité d'Endocrinologie Pédiatrique, Clinique de Pédiatrie, CHRU Lille,² Service d'Endocrinologie et Maladies Métaboliques, Clinique Marc Linquette, CHRU Lille,³ INSERM U560, Place de Verdun, Lille, France,⁵ Department of Molecular Biosciences, Swedish University of Agriculture Sciences Biomedical Center, Uppsala, Sweden⁴

Received 25 March 2005/ Accepted 3 August 2005

Coxsackievirus B4 (CVB4)-induced production of alpha interferon (IFN-) 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- 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°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- synthesis. There was no cross-reaction between VP4_CVB4 and VP4_CVB3 in the inhibiting effect. IFN- 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- 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- synthesis by PBMC.

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* Corresponding author. Mailing address: Service de Virologie/ UPRES EA3610, Faculté de Médecine, Université Lille 2, Bâtiment Paul Boulanger, CHRU Lille, 59037 Lille, France. Phone: 33 3 20 44 69 30. Fax: 33 3 20 44 52 81. E-mail: dhober{at}chru-lille.fr.

Present address: Department of Microbiology, Faculty of Medicine, Health Science Center, Kuwait University, P.O. Box 24923, 13110 Kuwait City, Kuwait.

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Journal of Virology, November 2005, p. 13882-13891, Vol. 79, No. 22
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.22.13882-13891.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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