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https://doi.org/10.15252/emmm.201404459
Title: | Loss of TLR3 aggravates CHIKV replication and pathology due to an altered virus-specific neutralizing antibody response | Authors: | Her, Z Teng, T.-S Tan, J.J.L Teo, T.-H Kam, Y.-W Lum, F.-M Lee, W.W.L Gabriel, C Melchiotti, R Andiappan, A.K Lulla, V Lulla, A Win, M.K Chow, A Biswas, S.K Leo, Y.-S Lecuit, M Merits, A Rénia, L Ng, L.F.P |
Keywords: | glycoprotein E2 neutralizing antibody toll like receptor 3 neutralizing antibody TLR3 protein, human TLR3 protein, mouse toll like receptor 3 virus antibody adult aged animal cell animal experiment animal model antibody response arthritis Article bone marrow cell cell infiltration chikungunya Chikungunya alphavirus controlled study disease severity female fibroblast genotype hematopoietic cell human human cell infection sensitivity innate immunity major clinical study male mouse nonhuman priority journal protein expression signal transduction single nucleotide polymorphism viral clearance virus load virus replication animal C57BL mouse chikungunya Chikungunya virus genetics immunology knockout mouse middle aged pathology physiology species difference virology young adult Adult Aged Animals Antibodies, Neutralizing Antibodies, Viral Chikungunya Fever Chikungunya virus Female Humans Male Mice Mice, Inbred C57BL Mice, Knockout Middle Aged Polymorphism, Single Nucleotide Species Specificity Toll-Like Receptor 3 Virus Replication Young Adult |
Issue Date: | 2015 | Citation: | Her, Z, Teng, T.-S, Tan, J.J.L, Teo, T.-H, Kam, Y.-W, Lum, F.-M, Lee, W.W.L, Gabriel, C, Melchiotti, R, Andiappan, A.K, Lulla, V, Lulla, A, Win, M.K, Chow, A, Biswas, S.K, Leo, Y.-S, Lecuit, M, Merits, A, Rénia, L, Ng, L.F.P (2015). Loss of TLR3 aggravates CHIKV replication and pathology due to an altered virus-specific neutralizing antibody response. EMBO Molecular Medicine 7 (1) : 24-41. ScholarBank@NUS Repository. https://doi.org/10.15252/emmm.201404459 | Abstract: | RNA-sensing toll-like receptors (TLRs) mediate innate immunity and regulate anti-viral response. We show here that TLR3 regulates host immunity and the loss of TLR3 aggravates pathology in Chikungunya virus (CHIKV) infection. Susceptibility to CHIKV infection is markedly increased in human and mouse fibroblasts with defective TLR3 signaling. Up to 100-fold increase in CHIKV load was observed in Tlr3-/- mice, alongside increased virus dissemination and pro-inflammatory myeloid cells infiltration. Infection in bone marrow chimeric mice showed that TLR3-expressing hematopoietic cells are required for effective CHIKV clearance. CHIKV-specific antibodies from Tlr3-/- mice exhibited significantly lower in vitro neutralization capacity, due to altered virus-neutralizing epitope specificity. Finally, SNP genotyping analysis of CHIKF patients on TLR3 identified SNP rs6552950 to be associated with disease severity and CHIKV-specific neutralizing antibody response. These results demonstrate a key role for TLR3-mediated antibody response to CHIKV infection, virus replication and pathology, providing a basis for future development of immunotherapeutics in vaccine development. © 2014 Agency for Science, Technology and Research (A*STAR). | Source Title: | EMBO Molecular Medicine | URI: | https://scholarbank.nus.edu.sg/handle/10635/174149 | ISSN: | 17574676 | DOI: | 10.15252/emmm.201404459 |
Appears in Collections: | Elements Staff Publications |
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