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马传染性贫血病毒的致病株和疫苗株在巨噬细胞中差异诱导细胞因子和趋化因子表达和凋亡。

The pathogenic and vaccine strains of equine infectious anemia virus differentially induce cytokine and chemokine expression and apoptosis in macrophages.

机构信息

State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.

出版信息

Virus Res. 2011 Sep;160(1-2):274-82. doi: 10.1016/j.virusres.2011.06.028. Epub 2011 Jul 14.

DOI:10.1016/j.virusres.2011.06.028
PMID:21782860
Abstract

The attenuated equine infectious anemia virus (EIAV) vaccine was the first attenuated lentivirus vaccine to be used in a large-scale application and has been used to successfully control the spread of equine infectious anemia (EIA) in China. To better understand the potential role of cytokines in the pathogenesis of EIAV infection and resulting immune response, we used branched DNA technology to compare the mRNA expression levels of 12 cytokines and chemokines, including IL-1α, IL-1β, IL-4, IL-10, TNF-α, IFN-γ, IP-10, IL-8, MIP-1α, MIP-1β, MCP-1, and MCP-2, in equine monocyte-derived macrophages (eMDMs) infected with the EIAV(DLV121) vaccine strain or the parental EIAV(DLV34) pathogenic strain. Infection with EIAV(DLV34) and EIAV(DLV121) both caused changes in the mRNA levels of various cytokines and chemokines in eMDMs. In the early stage of infection with EIAV(DLV34) (0-24h), the expression of the pro-inflammatory cytokines TNF-α and IL-1β were significantly up-regulated, while with EIAV(DLV121), expression of the anti-inflammatory cytokine IL-4 was markedly up-regulated. The effects on the expression of other cytokines and chemokines were similar between these two strains of virus. During the first 4 days after infection, the expression level of IL-4 in cells infected with the pathogenic strain were significantly higher than that in cells infected with the vaccine strain, but the expression of IL-1α and IL-1β induced by the vaccine strain was significantly higher than that observed with the pathogenic strain. In addition, after 4 days of infection with the pathogenic strain, the expression levels of 5 chemokines, but not IP-10, were markedly increased in eMDMs. In contrast, the vaccine strain did not up-regulate these chemokines to this level. Contrary to our expectation, induced apoptosis in eMDMs infected with the vaccine strain was significantly higher than that infected with the pathogenic strain 4 days and 6 days after infection. Together, these results contribute to a greater understanding of the pathogenesis of EIAV and of the mechanisms by which the immune response is induced after EIAV infection.

摘要

弱毒马传染性贫血病毒(EIAV)疫苗是首个用于大规模应用的减毒慢病毒疫苗,已成功用于控制中国马传染性贫血(EIA)的传播。为了更好地了解细胞因子在 EIAV 感染和由此产生的免疫反应中的潜在作用,我们使用分枝 DNA 技术比较了感染 EIAV(DLV121)疫苗株或亲本 EIAV(DLV34)致病株的马单核细胞衍生巨噬细胞(eMDMs)中 12 种细胞因子和趋化因子的 mRNA 表达水平,包括 IL-1α、IL-1β、IL-4、IL-10、TNF-α、IFN-γ、IP-10、IL-8、MIP-1α、MIP-1β、MCP-1 和 MCP-2。感染 EIAV(DLV34)和 EIAV(DLV121)均导致 eMDMs 中各种细胞因子和趋化因子的 mRNA 水平发生变化。在感染 EIAV(DLV34)的早期(0-24 小时),促炎细胞因子 TNF-α 和 IL-1β 的表达显著上调,而 EIAV(DLV121)感染时抗炎细胞因子 IL-4 的表达明显上调。两种病毒株对其他细胞因子和趋化因子表达的影响相似。在感染后 4 天内,感染致病株的细胞中 IL-4 的表达水平明显高于感染疫苗株的细胞,但疫苗株诱导的 IL-1α 和 IL-1β 的表达明显高于观察到的致病株。此外,感染致病株 4 天后,eMDMs 中 5 种趋化因子(IP-10 除外)的表达水平明显增加,但疫苗株并未将这些趋化因子上调至如此水平。与我们的预期相反,感染疫苗株的 eMDMs 在感染后 4 天和 6 天的凋亡诱导明显高于感染致病株的 eMDMs。综上所述,这些结果有助于更好地了解 EIAV 的发病机制,以及 EIAV 感染后免疫反应的诱导机制。

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