Effect of betulinic acid and its ionic derivatives on M-MuLV replication.

Effect of betulinic acid and its ionic derivatives on M-MuLV replication.
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DOI:
10.1016/j.bbrc.2018.04.080
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发表时间:
2018-06-02
影响因子:
3.1
通讯作者:
Nitta T
Nitta T
中科院分区:
生物学4区
文献类型:
--
作者:
Phillips J;Phillips I;Enya B;Zhao H;Nitta T

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小鼠白血病病毒(MuLV)是一种已知可引起小鼠白血病和神经系统疾病的逆转录病毒,其病毒生命周期和发病机制在过去几十年中被广泛研究。作为一种天然的抗病毒药物,白桦酸是一种五环三萜,可以在几种植物(特别是白桦树)的树皮中找到。白桦酸释放其抗病毒效力的障碍之一是其水溶性差。在本研究中,我们合成了更多的水溶性白桦酸离子衍生物,并检测了它们对Moloney MuLV (M-MuLV)的活性。用不同剂量的白桦酸及其衍生物处理稳定感染M-MuLV的小鼠成纤维细胞(43D细胞),用western blots检测细胞和培养基中的病毒结构蛋白Gag。发现含有苯扎康铵阳离子的两个离子衍生物抑制病毒在培养基中的产生并降低细胞中的Gag。然而,细胞增殖试验显示,苯扎康铵阳离子抑制了43D细胞的生长,这表明我们的离子衍生物通过抑制43D细胞的代谢来限制病毒的产生。有趣的是,所有这些白桦酸化合物对43D细胞中Gag的加工和释放的影响最小,这概述了MuLV和人类免疫缺陷病毒之间病毒成熟的差异。
Murine leukemia virus (MuLV) is a retrovirus known causing leukemia and neurological disorders in mice, and its viral life cycle and pathogenesis have been investigated extensively over the past decades. As a natural antiviral agent, betulinic acid is a pentacyclic triterpenoid that can be found in the bark of several species of plants (particularly the white birch). One of the hurdles for betulinic acid to release its antiviral potency is its poor water solubility. In this study, we synthesized more water-soluble ionic derivatives of betulinic acid, and examined their activities against Moloney MuLV (M-MuLV). The mouse fibroblast cells stably infected with M-MuLV, 43D cells, were treated with various doses of betulinic acids and its derivatives, and the viral structural protein Gag in cells and media were detected by western blots. Two ionic derivatives containing the benzalkonium cation were found to inhibit the virus production into media and decreased Gag in cells. However, a cell proliferation assay showed that the benzalkonium cation inhibited the growth of 43D cells, suggesting that our ionic derivatives limited virus production through the inhibition of metabolism in 43D cells. Interestingly, all of these betulinic acid compounds exhibited a minimum impact on the processing and release of Gag from 43D cells, which outlines the differences of viral maturation between MuLV and human immunodeficiency virus.
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