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    TLR3 and RIG-I gene variants: Associations with functional effects on receptor expression and responses to measles virus and vaccine in vaccinated infants

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    Authors
    Clifford, H.
    Yerkovich, S.
    Khoo, S.
    Zhang, Guicheng
    Upham, J.
    Le Souëf, P.
    Richmond, P.
    Hayden, C.
    Date
    2012
    Type
    Journal Article
    
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    Citation
    Clifford, H. and Yerkovich, S. and Khoo, S. and Zhang, G. and Upham, J. and Le Souëf, P. and Richmond, P. et al. 2012. TLR3 and RIG-I gene variants: Associations with functional effects on receptor expression and responses to measles virus and vaccine in vaccinated infants. Human Immunology. 73 (6): pp. 677-685.
    Source Title
    Human Immunology
    DOI
    10.1016/j.humimm.2012.03.004
    ISSN
    0198-8859
    School
    School of Public Health
    URI
    http://hdl.handle.net/20.500.11937/21346
    Collection
    • Curtin Research Publications
    Abstract

    Measles virus causes severe morbidity and mortality, despite the availability of measles vaccines. Successful defence against viral pathogens requires early recognition of virus-specific patterns by innate receptors like Toll-like receptor (TLR)3 and the RNA helicase, retinoic acid inducible gene-I (RIG-I). Genetic differences in these receptors may influence the primary immune responses to measles and the efficacy of measles vaccine. In 1-year-old Australian infants after their first measles vaccine dose, we investigated functional effects of TLR3 and RIG-I polymorphisms on intracellular protein expression using flow cytometry, cytokine responses to receptor ligands and measles lysate, and post-vaccination measles IgG levels. We found that TLR3 Leu412Phe was significantly associated with IFN-a/ß response after stimulation with TLR3 ligand, poly(I:C) (P= 0.024). Downregulation of TLR3 protein expression in NK cells after poly(I:C) was also associated with this variant (P= 0.011). In contrast, measles-specific expression, cytokine responses and antibody responses were not associated with TLR3 polymorphisms. No associations were found with RIG-I variants. These results suggest that a TLR3 polymorphism has functional effects on receptor expression and cytokine response. However, this did not translate to an effect on specific responses to measles virus or vaccine. We found no evidence that RIG-I polymorphisms were involved in measles immune responses. © 2012.

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