Toll-like receptor responses to Peste des petits ruminants virus in goats and water buffalo.
Toll-like receptor responses to Peste des petits ruminants virus in goats and water buffalo.
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DOI：
10.1371/journal.pone.0111609
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Elankumaran S
中科院分区：
文献类型：
--
作者：
Dhanasekaran S;Biswas M;Vignesh AR;Ramya R;Raj GD;Tirumurugaan KG;Raja A;Kataria RS;Parida S;Elankumaran S
绵羊牛瘟或山羊瘟疫是一种由小反刍动物疫病病毒(Pust des Pust des Referants Virus，PPRV)引起的绵羊和山羊的传染性疾病，具有重要的经济意义。不同品种和不同水牛对山羊鼠疫的易感性存在差异。宿主的先天免疫系统通过被称为Toll样受体(TLR)的监视受体来区分病原体相关的分子模式和自身抗原。我们研究了TLR和细胞因子在山羊品种和水牛对猪繁殖与呼吸综合征病毒不同易感性中的作用。我们检测了PPRV在印度家山羊和水牛外周血单个核细胞(PBMC)中的复制情况，发现TLR3和TLR7及其下游信号分子的水平与敏感性和耐药性有关。自然易感的山羊品种Barbari和Tellichery在转录水平上抑制了对PPRV的天然免疫反应，并增加了病毒载量，TLR3/7的基础表达水平较低。合成的TLR3和TLR7激动剂或PPRV刺激PBMC后，抗PPRV的Kanni和Salem Black品种和水牛的促炎细胞因子水平显著升高，而免疫抑制白介素10(IL)10的水平降低，这与感染PPRV的PBMC中的病毒载量减少有关。与山羊相比，水牛在转录和翻译水平上产生更高水平的干扰素α。用人干扰素α处理VERO细胞后，PPRV复制减少，证实了干扰素α在限制PPRV复制中的作用。用TLR7拮抗剂IRS66治疗后，干扰素α水平降低，PPRV复制增加，证实了TLR7的作用。对这些山羊品种TLR7的单核苷酸多态性分析没有发现任何可能解释对猪繁殖与呼吸综合征病毒易感性和抗药性的显著核苷酸差异。分析宿主的其他遗传因素可能会进一步了解宿主对PPRV的易感性和遗传多态性。
Ovine rinderpest or goat plague is an economically important and contagious viral disease of sheep and goats, caused by the Peste des petits ruminants virus (PPRV). Differences in susceptibility to goat plague among different breeds and water buffalo exist. The host innate immune system discriminates between pathogen associated molecular patterns and self antigens through surveillance receptors known as Toll like receptors (TLR). We investigated the role of TLR and cytokines in differential susceptibility of goat breeds and water buffalo to PPRV. We examined the replication of PPRV in peripheral blood mononuclear cells (PBMC) of Indian domestic goats and water buffalo and demonstrated that the levels of TLR3 and TLR7 and downstream signalling molecules correlation with susceptibility vs resistance. Naturally susceptible goat breeds, Barbari and Tellichery, had dampened innate immune responses to PPRV and increased viral loads with lower basal expression levels of TLR 3/7. Upon stimulation of PBMC with synthetic TLR3 and TLR7 agonists or PPRV, the levels of proinflammatory cytokines were found to be significantly higher while immunosuppressive interleukin (IL) 10 levels were lower in PPRV resistant Kanni and Salem Black breeds and water buffalo at transcriptional level, correlating with reduced viralloads in infected PBMC. Water buffalo produced higher levels of interferon (IFN) α in comparison with goats at transcriptional and translational levels. Pre-treatment of Vero cells with human IFNα resulted in reduction of PPRV replication, confirming the role of IFNα in limiting PPRV replication. Treatment with IRS66, a TLR7 antagonist, resulted in the reduction of IFNα levels, with increased PPRV replication confirming the role of TLR7. Single nucleotide polymorphism analysis of TLR7 of these goat breeds did not show any marked nucleotide differences that might account for susceptibility vs resistance to PPRV. Analyzing other host genetic factors might provide further insights on susceptibility to PPRV and genetic polymorphisms in the host.
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