Foot-and-mouth disease virus localisation on follicular dendritic cells and sustained induction of neutralising antibodies is dependent on binding to complement receptors (CR2/CR1) |
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| Authors: | Lucy Gordon Neil Mabbott Joanna Wells Liudmila Kulik Nick Juleff Bryan Charleston Eva Perez-Martin |
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| Affiliation: | 1. The Pirbright Institute, Woking, United Kingdom;2. The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, United Kingdom;3. Division of Rheumatology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, United States of America;4. Bill and Melinda Gates Foundation, Seattle, Washington, United States of America; Moderna Therapeutics Inc, UNITED STATES |
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| Abstract: | Previous studies have shown after the resolution of acute infection and viraemia, foot-and-mouth disease virus (FMDV) capsid proteins and/or genome are localised in the light zone of germinal centres of lymphoid tissue in cattle and African buffalo. The pattern of staining for FMDV proteins was consistent with the virus binding to follicular dendritic cells (FDCs). We have now demonstrated a similar pattern of FMDV protein staining in mouse spleens after acute infection and showed FMDV proteins are colocalised with FDCs. Blocking antigen binding to complement receptor type 2 and 1 (CR2/CR1) prior to infection with FMDV significantly reduced the detection of viral proteins on FDCs and FMDV genomic RNA in spleen samples. Blocking the receptors prior to infection also significantly reduced neutralising antibody titres, through significant reduction in their avidity to the FMDV capsid. Therefore, the binding of FMDV to FDCs and sustained induction of neutralising antibody responses are dependent on FMDV binding to CR2/CR1 in mice. |
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