PDF(Pubmed)
Abstract：
Borna disease virus 1 (BoDV1) causes a persistent infection in the mammalian brain. Peroxisomes and mitochondria play essential roles in the cellular antiviral immune response, but the effect of BoDV1 infection on peroxisomal and mitochondrial dynamics and their respective antioxidant capacities is still not clear. Using different mouse lines-i.e., tumor necrosis factor-α transgenic (TNFTg; to pro-inflammatory status), TNF receptor-1 knockout (TNFR1ko), and TNFR2ko mice in comparison to wild-type (Wt) mice-we analyzed the abundances of both organelles and their main antioxidant enzymes, catalase and superoxide dismutase 2 (SOD2), in neurons of the hippocampal, cerebral, and cerebellar cortices. In TNFTg mice, a strong increase in mitochondrial (6.9-fold) and SOD2 (12.1-fold) abundances was detected; meanwhile, peroxisomal abundance increased slightly (1.5-fold), but that of catalase decreased (2.9-fold). After BoDV1 infection, a strong decrease in mitochondrial (2.1-6.5-fold), SOD2 (2.7-9.1-fold), and catalase (2.7-10.3-fold) abundances, but a slight increase in peroxisomes (1.3-1.6-fold), were detected in Wt and TNFR2ko mice, whereas no changes occurred in TNFR1ko mice. Our data suggest that the TNF system plays a crucial role in the biogenesis of both subcellular organelles. Moreover, TNFR1 signaling mediated the changes in peroxisomal and mitochondrial dynamics after BoDV1 infection, highlighting new mechanisms by which BoDV1 may achieve immune evasion and viral persistence.
摘要：
博尔纳病病毒1（BodV1）在哺乳动物大脑中引起持续感染。过氧化物酶体和线粒体在细胞抗病毒免疫反应中发挥重要作用，但BoDV1感染对过氧化物酶体和线粒体动力学及其各自抗氧化能力的影响仍不清楚。使用不同的鼠标行-即，肿瘤坏死因子-α转基因（TNFTG；促炎状态），TNF受体-1基因敲除(TNFR1ko),和TNFR2ko小鼠与野生型（Wt）小鼠相比，我们分析了两种细胞器及其主要抗氧化酶的丰度，过氧化氢酶和超氧化物歧化酶2（SOD2），在海马的神经元中，大脑，和小脑皮质.在TNFTg小鼠中，检测到线粒体（6.9倍）和SOD2（12.1倍）丰度的强烈增加；同时，过氧化物酶体丰度略有增加（1.5倍），但是过氧化氢酶的含量下降了（2.9倍）。BoDV1感染后,线粒体的强烈减少（2.1-6.5倍），SOD2（2.7-9.1倍），和过氧化氢酶(2.7-10.3倍)丰度，但过氧化物酶体略有增加（1.3-1.6倍），在Wt和TNFR2ko小鼠中检测到，而在TNFR1ko小鼠中没有发生改变。我们的数据表明，TNF系统在两个亚细胞细胞器的生物发生中起着至关重要的作用。此外，TNFR1信号介导BodV1感染后过氧化物酶体和线粒体动力学的变化，强调BoDV1可能实现免疫逃避和病毒持续存在的新机制。
