Department of Chemistry and Forensic Science, Savannah State University, 3219 College St., Savannah, GA 31404, USA.
Department of Biology, Savannah State University, 3219 College St., Savannah, GA 31404, USA.
Biochem Biophys Res Commun. 2018 Jun 2;500(2):365-369. doi: 10.1016/j.bbrc.2018.04.080. Epub 2018 Apr 21.
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.
鼠白血病病毒（MuLV）是一种逆转录病毒，已知会导致小鼠白血病和神经紊乱，其病毒生命周期和发病机制在过去几十年中得到了广泛研究。作为一种天然抗病毒剂，白桦脂酸是一种五环三萜，可以在几种植物（尤其是白桦）的树皮中找到。白桦脂酸释放其抗病毒效力的一个障碍是其较差的水溶性。在这项研究中，我们合成了更多水溶性的白桦脂酸离子衍生物，并研究了它们对莫洛尼鼠白血病病毒（M-MuLV）的活性。用各种剂量的白桦脂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，通过 Western blot 检测细胞和培养基中病毒结构蛋白 Gag。发现两种含有苯扎氯铵阳离子的离子衍生物能够抑制病毒进入培养基中的产量，并减少细胞中的 Gag。然而，细胞增殖测定表明苯扎氯铵阳离子抑制了 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，所有这些白桦脂酸化合物对 Gag 从 43D 细胞中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。
