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.
Bergthaler
Andreas
A
Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland. andreas.bergthaler@gmail.com
Flatz
Lukas
L
Verschoor
Admar
A
Hegazy
Ahmed N
AN
Holdener
Martin
M
Fink
Katja
K
Eschli
Bruno
B
Merkler
Doron
D
Sommerstein
Rami
R
Horvath
Edit
E
Fernandez
Marylise
M
Fitsche
André
A
Senn
Beatrice M
BM
Verbeek
J Sjef
JS
Odermatt
Bernhard
B
Siegrist
Claire-Anne
CA
Pinschewer
Daniel D
DD
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