Alché Laura E, Barquero Andrea A, Sanjuan Norberto A, Coto Celia E
Laboratory of Virology, Department of Biochemistry, School of Science, University of Buenos Aires, Pabellón II, Piso 4to, Ciudad Universitaria, 1428 Buenos Aires, Argentina.
Phytother Res. 2002 Jun;16(4):348-52. doi: 10.1002/ptr.895.
Meliacine (MA), an antiviral principle isolated from leaves of Melia azedarach L., exhibits potent antiviral activity against herpes simplex virus type 1 (HSV-1) by inhibiting specific infected-cell polypeptides (ICPs) produced late in infection. Some of these are involved in DNA synthesis and in the assembly of nucleocapsids. The present report provides additional evidence to elucidate the mode of action of MA against HSV-1. Time-of-addition experiments confirmed that MA affects a late event in the multiplication cycle of HSV-1. We showed that MA diminished the synthesis of viral DNA and inhibited the spread of infectious viral particles when HSV-1 that expresses beta-galactosidase activity was used. In addition, the lack of a protein with an apparent MW of 55 KD was detected in MA-treated cell extracts. Ultrastructural analysis of infected cells showed that, in the case of MA treatment, a large number of unenveloped nucleocapsids accumulated in the cytoplasm and a minor proportion of mature virus was found in cytoplasmic vesicles.These findings suggest that MA exerts an antiviral action on both the synthesis of viral DNA and the maturation and egress of HSV-1 during the infection of Vero cells.
苦楝素（MA）是从苦楝树叶中分离出的一种抗病毒成分，通过抑制感染后期产生的特定感染细胞多肽（ICP），对单纯疱疹病毒1型（HSV-1）表现出强大的抗病毒活性。其中一些多肽参与DNA合成和核衣壳组装。本报告提供了更多证据以阐明MA对HSV-1的作用方式。添加时间实验证实，MA影响HSV-1增殖周期中的一个晚期事件。我们发现，当使用表达β-半乳糖苷酶活性的HSV-1时，MA减少了病毒DNA的合成并抑制了感染性病毒颗粒的传播。此外，在MA处理的细胞提取物中检测到缺乏一种表观分子量为55 KD的蛋白质。对感染细胞的超微结构分析表明，在MA处理的情况下，大量无包膜的核衣壳积聚在细胞质中，并且在细胞质囊泡中发现了少量成熟病毒。这些发现表明，MA在Vero细胞感染期间对病毒DNA合成以及HSV-1的成熟和释放均发挥抗病毒作用。
