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Polyamine regulation of porcine reproductive and respiratory syndrome virus infection depends on spermidine-spermine acetyltransferase 1
Veterinary Microbiology ( IF 3.3 ) Pub Date : 2020-09-19 , DOI: 10.1016/j.vetmic.2020.108839
Yanrong Zhou 1 , Zhenzhen Hou 1 , Liurong Fang 1 , Qiyun Ke 1 , Yujian Xiong 1 , Puxian Fang 1 , Shaobo Xiao 1
Affiliation  

Like obligate intracellular parasites, viruses co-opt host cell resources to establish productive infections. Polyamines are key aliphatic molecules that perform important roles in cellular growth and proliferation. They are also needed for the successful multiplication of various viruses. Little is known about the effects of polyamines on Arteriviridae infections. Here, porcine reproductive and respiratory syndrome virus (PRRSV), an economically prominent porcine virus, was used to investigate virus–polyamine interactions. We found that PRRSV infection significantly downregulated the levels of cellular polyamines. Using an inhibitor or specific short interfering RNAs (siRNAs) of ornithine decarboxylase 1, a key anabolic enzyme involved in the classical de novo biosynthesis of polyamines, we found that polyamine depletion abrogated PRRSV proliferation, and this effect was recoverable by adding exogenous spermidine and spermine, but not putrescine to the cells, suggesting that the host inhibits polyamine biosynthesis to restrict PRRSV proliferation. Further analysis revealed that the expression level of spermidine-spermine acetyltransferase 1 (SAT1), a catabolic enzyme that reduces spermidine and spermine levels, was upregulated during PRRSV infection, but conversely, SAT1 had an inhibitory effect on PRRSV reproduction. Our data show that polyamines are important molecules during PRRSV-host interactions, and polyamines and their biosynthetic pathways are potential therapeutic targets against PRRSV infection.



中文翻译:

多胺对猪生殖和呼吸综合征病毒感染的调节取决于亚精胺-精胺乙酰转移酶1

像专性细胞内寄生虫一样,病毒会选择宿主细胞资源来建立生产性感染。多胺是在细胞生长和增殖中起重要作用的关键脂肪族分子。成功繁殖各种病毒也需要它们。关于多胺对Arteriviridae感染的影响知之甚少。在这里,猪繁殖与呼吸综合症病毒(PRRSV)是一种经济上很重要的猪病毒,用于研究病毒与多胺的相互作用。我们发现PRRSV感染显着下调了细胞中多胺的水平。使用鸟氨酸脱羧酶1的抑制剂或特定的短干扰RNA(siRNA),这是参与多胺经典从头生物合成的关键合成代谢酶,我们发现多胺消耗消除了PRRSV的增殖,并且通过向细胞中加入外源亚精胺和亚精胺而不是腐胺可以恢复这种作用,这表明宿主抑制了多胺的生物合成以限制PRRSV的增殖。进一步的分析表明,在PRRSV感染期间,亚精胺-精胺乙酰转移酶1(SAT1)(一种降低亚精胺和精胺水平的分解代谢酶)的表达水平上调,但相反,SAT1对PRRSV繁殖具有抑制作用。我们的数据表明,多胺是PRRSV-宿主相互作用过程中的重要分子,多胺及其生物合成途径是抗PRRSV感染的潜在治疗靶标。提示宿主抑制多胺生物合成以限制PRRSV增殖。进一步的分析表明,在PRRSV感染期间,亚精胺-精胺乙酰转移酶1(SAT1)(一种降低亚精胺和精胺水平的分解代谢酶)的表达水平上调,但相反,SAT1对PRRSV繁殖具有抑制作用。我们的数据表明,多胺是PRRSV与宿主相互作用期间的重要分子,多胺及其生物合成途径是抗PRRSV感染的潜在治疗靶标。提示宿主抑制多胺生物合成以限制PRRSV增殖。进一步的分析表明,在PRRSV感染期间,亚精胺-精胺乙酰转移酶1(SAT1)(一种降低亚精胺和精胺水平的分解代谢酶)的表达水平上调,但相反,SAT1对PRRSV繁殖具有抑制作用。我们的数据表明,多胺是PRRSV-宿主相互作用过程中的重要分子,多胺及其生物合成途径是抗PRRSV感染的潜在治疗靶标。SAT1对PRRSV的繁殖具有抑制作用。我们的数据表明,多胺是PRRSV-宿主相互作用过程中的重要分子,多胺及其生物合成途径是抗PRRSV感染的潜在治疗靶标。SAT1对PRRSV的繁殖具有抑制作用。我们的数据表明,多胺是PRRSV-宿主相互作用过程中的重要分子,多胺及其生物合成途径是抗PRRSV感染的潜在治疗靶标。

更新日期:2020-09-29
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