【摘 要】
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Toll-like receptor-3 (TLR-3) is a transmembrane signaling protein expressed in dendritic cells,macrophages and natural killer cells and recognizes nucleic acids (double stranded RNA).The binding of ds
【机 构】
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Defence Research & Development Canada-Suffield Canada
【出 处】
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中国上海第七届国际新药发明科技年会
论文部分内容阅读
Toll-like receptor-3 (TLR-3) is a transmembrane signaling protein expressed in dendritic cells,macrophages and natural killer cells and recognizes nucleic acids (double stranded RNA).The binding of ds RNA to TLR-3 activates the TLR-3 signaling pathway which in turns mediates both the antiviral and inflammatory responses of the innate immunity to combat viral infections.This presentation focuses on the antiviral role of synthetic ds RNAs as TLR-3 agonists for the protection against seasonal and avian influenza viruses.Poly ICLC is a synthetic double stranded RNA comprising of polyriboinosinic-polyribocytidylic acid (Poly IC) stabilized with L-lysine (L) and carboxymethylcellulose (C).Poly ICLC and liposome-encapsulated Poly ICLC (LE Poly ICLC) are TLR-3 agonists and are potent inducer of interferons and natural killer cells.Intranasal pre-treatment of mice with Poly ICLC and LE Poly ICLC provided high level of protection against lethal challenge with a highly lethal HPAI strain (A/H5N1/chicker/Henan clade 2),and against seasonal influenza A/PR/8/34 [H1N1] and A/Aichi/2 [H3N2] virus strains.The duration of protective antiviral immunity to multiple lethal doses of influenza virus A/PR/8/34 virus had been previously found to persist for up to 3 weeks in mice for LE Poly ICLC and two weeks for Poly ICLC.
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