Nonneutralizing antibodies binding to the surface glycoprotein of lymphocytic choriomeningitis virus reduce early virus spread.
The biological relevance of nonneutralizing antibodies elicited early after infection with noncytopathic persistence-prone viruses is unclear. We demonstrate that cytotoxic T lymphocyte-deficient TgH(KL25) mice, which are transgenic for the heavy chain of the lymphocytic choriomeningitis virus (LCMV)-neutralizing monoclonal antibody KL25, mount a focused neutralizing antibody response following LCMV infection, and that this results in the emergence of neutralization escape virus variants. Further investigation revealed that some of the escape variants that arose early after infection could still bind to the selecting antibody. In contrast, no antibody binding could be detected for late isolates, indicating that binding, but nonneutralizing, antibodies exerted a selective pressure on the virus. Infection of naive TgH(KL25) mice with distinct escape viruses differing in their antibody-binding properties revealed that nonneutralizing antibodies accelerated clearance of antibody-binding virus variants in a partly complement-dependent manner. Virus variants that did not bind antibodies were not affected. We therefore conclude that nonneutralizing antibodies binding to the same antigenic site as neutralizing antibodies are biologically relevant by limiting early viral spread.
Hangartner
Lars
L
Institute of Experimental Immunology, University Hospital Zürich, 8091 Zürich, Switzerland. lhangart@scripps.edu
Zellweger
Raphaël M
RM
Giobbi
Mattia
M
Weber
Jacqueline
J
Eschli
Bruno
B
McCoy
Kathy D
KD
Harris
Nicola
N
Recher
Mike
M
Zinkernagel
Rolf M
RM
Hengartner
Hans
H
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001666:Binding Sites, Antibody / Q000276:immunology*; D003167:Complement Activation / Q000276:immunology; D006023:Glycoproteins / Q000737:chemistry / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000821:virology*; D008217:Lymphocytic choriomeningitis virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology*
D000914:Antibodies, Viral; D000956:Antigens, Viral; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D014764:Viral Proteins