Impaired antibody response causes persistence of prototypic T cell-contained virus

  • CD8 T cells are recognized key players in control of persistent virus infections, but increasing evidence suggests that assistance from other immune mediators is also needed. Here, we investigated whether specific antibody responses contribute to control of lymphocytic choriomeningitis virus (LCMV), a prototypic mouse model of systemic persistent infection. Mice expressing transgenic B cell receptors of LCMV-unrelated specificity, and mice unable to produce soluble immunoglobulin M (IgM) exhibited protracted viremia or failed to resolve LCMV. Virus control depended on immunoglobulin class switch, but neither on complement cascades nor on Fc receptor gamma chain or Fc gamma receptor IIB. Cessation of viremia concurred with the emergence of viral envelope-specific antibodies, rather than with neutralizing serum activity, and even early nonneutralizing IgM impeded viral persistence. This important role for virus-specific antibodies may be similarly underappreciated in other primarily T cell–controlled infections such as HIV and hepatitis C virus, and we suggest this contribution of antibodies be given consideration in future strategies for vaccination and immunotherapy.
Author:Andreas Bergthaler, Lukas Flatz, Admar Verschoor, Ahmed N. Hegazy, Martin Holdener, Katja Fink, Bruno Eschli, Doron Merkler, Rami Sommerstein, Edit Horvath, Marylise Fernandez, André Fitsche, Beatrice M. Senn, J. Sjef Verbeek, Bernhard Odermatt, Claire-Anne Siegrist, Daniel D. Pinschewer
Parent Title (English):PLoS biology
Place of publication:Lawrence, Kan.
Document Type:Article
Date of Publication (online):2009/04/07
Date of first Publication:2009/04/07
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2009/08/11
Issue:(4): e1000080
Page Number:11
First Page:789
Last Page:799
Copyright: © 2009 Bergthaler et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 3.0