State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 427, Maduan Street, Nangang District, Harbin 150001, China.
Vet Microbiol. 2013 Sep 27;166(1-2):263-9. doi: 10.1016/j.vetmic.2013.06.005. Epub 2013 Jun 21.
Activations of endosomal TLRs include TLR3, TLR7/8, and TLR9 stimulates the production of cytokines, such as type I interferons (IFNs), and therefore involves in virus-host interactions. In the present study, two equine anemia virus (EIAV) strains EIAVFDDV13 and EIAVFDDV3-8, which showed different induction on protective immunity, were compared regarding their ability to regulate the expression of endosomal TLRs, as well as type I IFNs, after infection of equine monocyte-derived macrophages (eMDMs). Our results showed that EIAVFDDV13 dramatically up-regulated the expression of TLR3 and IFNβ and less robustly up-regulated the expression of TRL9 and IFNα1, whereas EIAVFDDV3-8 induced significantly lower expression of type I IFN mRNA and protein and more strongly down-regulated the expression of TLR7 and TLR8. In addition, no significant differences in cell apoptosis were observed between these two strains. Given that the genomic variation of EIAVFDDV13 is considerably higher than that of molecular clone EIAVFDDV3-8, our results suggest that stronger TLR3 activation and increased INFβ production induced by the multi-species strain are associated with an effective vaccine-elicited protective immune response.
内体 TLR 的激活包括 TLR3、TLR7/8 和 TLR9,可刺激细胞因子(如 I 型干扰素)的产生,因此参与病毒-宿主相互作用。在本研究中,我们比较了两株具有不同诱导保护性免疫能力的马贫血病毒(EIAV)毒株 EIAVFDDV13 和 EIAVFDDV3-8,分析它们在感染马单核细胞衍生巨噬细胞(eMDMs)后,调节内体 TLR 以及 I 型 IFN 的表达的能力。结果表明,EIAVFDDV13 可显著上调 TLR3 和 IFNβ 的表达,较弱地上调 TLR9 和 IFNα1 的表达,而 EIAVFDDV3-8 则诱导较低水平的 I 型 IFN mRNA 和蛋白表达,并且强烈下调 TLR7 和 TLR8 的表达。此外,这两种毒株之间未观察到细胞凋亡的显著差异。鉴于 EIAVFDDV13 的基因组变异明显高于分子克隆 EIAVFDDV3-8,我们的结果表明,多物种毒株诱导的更强 TLR3 激活和增加的 INFβ 产生与有效的疫苗诱导的保护性免疫反应有关。