Publication

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

Journal Paper/Review - Apr 7, 2009

Units
PubMed
Doi

Citation
Bergthaler A, Siegrist C, Odermatt B, Verbeek J, Senn B, Fitsche A, Fernandez M, Horvath E, Sommerstein R, Merkler D, Eschli B, Fink K, Holdener M, Hegazy A, Verschoor A, Flatz L, Pinschewer D. Impaired antibody response causes persistence of prototypic T cell-contained virus. PLoS Biol 2009; 7:e1000080.
Type
Journal Paper/Review (English)
Journal
PLoS Biol 2009; 7
Publication Date
Apr 7, 2009
Issn Electronic
1545-7885
Pages
e1000080
Brief description/objective

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.