Nonneutralizing antibodies binding to the surface glycoprotein of lymphocytic choriomeningitis virus reduce early virus spread

Autor: Lars Hangartner, Hans Hengartner, Nicola L. Harris, Mike Recher, Rolf M. Zinkernagel, Mattia Giobbi, Raphaël M. Zellweger, Jacqueline Weber, Kathy D. McCoy, Bruno Eschli
Rok vydání: 2006
Předmět:
viruses
Antibodies
Viral
Neutralization
Mice
0302 clinical medicine
Antibodies
Viral/*immunology
Lymphocytic choriomeningitis virus
Immunology and Allergy
Cytotoxic T cell
virus/chemistry/genetics/*immunology/*physiology
Neutralizing antibody
Antigens
Viral
Complement Activation
B-Lymphocytes
0303 health sciences
Membrane Glycoproteins
Viral Proteins/chemistry/*immunology
B-Lymphocytes/immunology
Articles
Recombinant Proteins
3. Good health
Binding Sites
Antibody/*immunology
Antigens
Viral/chemistry/immunology
Antibody
medicine.drug_class
Immunology
Lymphocytic Choriomeningitis
Biology
Lymphocytic choriomeningitis
Monoclonal antibody
Article
Virus
Viral Proteins
03 medical and health sciences
Membrane Glycoproteins/*metabolism
Antigen
Lymphocytic Choriomeningitis/*virology
Neutralization Tests
medicine
Animals
Glycoproteins/chemistry/immunology
Recombinant Proteins/immunology
Glycoproteins
030304 developmental biology
Complement Activation/immunology
T-Lymphocytes
Cytotoxic/immunology
medicine.disease
Virology
Mice
Inbred C57BL
biology.protein
Binding Sites
Antibody
T-Lymphocytes
Cytotoxic
030215 immunology
Zdroj: The Journal of Experimental Medicine
ISSN: 1540-9538
0022-1007
DOI: 10.1084/jem.20051557
Popis: 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.
Databáze: OpenAIRE
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