Programa de Estudio y Control de Enfermedades Tropicales, Medellín, Colombia.
Intervirology. 2011;54(4):202-16. doi: 10.1159/000321892. Epub 2011 Feb 4.
Most of the effects of statins can be explained by pleiotropic effects independent of their lowering of serum cholesterol; in some cases, these effects have been shown to be a result of the role of statins in the prenylation of cellular proteins, some of which are involved in the life cycle of animal viruses. This study evaluated the potential antiviral activity of lovastatin (LOV) against dengue virus (DENV) infection of epithelial and endothelial cells (VERO cells, epithelial cells derived from African green monkey kidney, and HMEC-1 cells, human dermal microvascular endothelial cells).
To evaluate its potential antiviral effects, LOV was used before, during and after inoculation of cell cultures with DENV.
Before and after viral inoculation, LOV caused a reduction in virus yield (80% for HMECs and 25% for VERO cells). However, with LOV treatment after inoculation induced a marked increase (2- to 9-fold) in viral-positive RNA while the amount of viral protein increased only by 13-23%. A moderate reduction (1 log unit) in viral titer occurred concurrent with the increase in DENV genomic RNA and protein within the cells.
According to our results, LOV appears to have a greater effect on viral assembly than on replication, resulting in the cellular presence of viral genomic RNA and proteins that fail to take the normal assembly pathway.
他汀类药物的大多数作用可以通过独立于降低血清胆固醇的多效作用来解释；在某些情况下，这些作用已被证明是他汀类药物在细胞蛋白的prenylation 中的作用的结果，其中一些参与动物病毒的生命周期。本研究评估了洛伐他汀（LOV）对上皮细胞和内皮细胞（VERO 细胞，源自非洲绿猴肾的上皮细胞和 HMEC-1 细胞，人真皮微血管内皮细胞）中登革热病毒（DENV）感染的潜在抗病毒活性。
为了评估其潜在的抗病毒作用，在接种 DENV 前后以及接种后使用 LOV 处理细胞培养物。
病毒接种前后，LOV 导致病毒产量减少（对 HMEC 为 80％，对 VERO 细胞为 25％）。然而，接种后用 LOV 处理会导致病毒阳性 RNA 显著增加（HMEC 为 2-9 倍，VERO 细胞为 2-9 倍），而病毒蛋白的量仅增加 13-23％。与细胞内 DENV 基因组 RNA 和蛋白质的增加同时发生病毒滴度适度降低（1 个对数单位）。
根据我们的结果，LOV 似乎对病毒组装的影响大于对复制的影响，导致细胞内存在无法采取正常组装途径的病毒基因组 RNA 和蛋白质。
