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.
Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland. andreas.bergthaler@gmail.com
Andreas
A
Bergthaler
Lukas
L
Flatz
Admar
A
Verschoor
Ahmed N
AN
Hegazy
Martin
M
Holdener
Katja
K
Fink
Bruno
B
Eschli
Doron
D
Merkler
Rami
R
Sommerstein
Edit
E
Horvath
Marylise
M
Fernandez
André
A
Fitsche
Beatrice M
BM
Senn
J Sjef
JS
Verbeek
Bernhard
B
Odermatt
Claire-Anne
CA
Siegrist
Daniel D
DD
Pinschewer
D000818:Animals; D000914:Antibodies, Viral / Q000502:physiology*; D001117:Arenaviridae Infections / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D003165:Complement System Proteins / Q000276:immunology; D004195:Disease Models, Animal; D017578:Immunoglobulin Class Switching / Q000502:physiology*; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011947:Receptors, Antigen, B-Cell; D019562:Viral Load; D014766:Viremia / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology*
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D003165:Complement System Proteins