Please use this identifier to cite or link to this item: 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
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