Laboratory of Experimental Virology, Department of Medical Microbiology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
PLoS One. 2007 May 23;2(5):e470. doi: 10.1371/journal.pone.0000470.
Statins have previously been shown to reduce the in vitro infection of human immunodeficiency virus type 1 (HIV-1) through modulation of Rho GTPase activity and lipid raft formation at the cell surface, as well as by disrupting LFA-1 incorporation into viral particles.
Here we demonstrate that treatment of an enriched CD4(+) lymphocyte population with lovastatin (Lov), mevastatin (Mev) and simvastatin (activated and non-activated, Sim(A) and Sim(N), respectively) can reduce the cell surface expression of the CC-chemokine receptor CCR5 (P<0.01 for Sim(A) and Lov). The lowered CCR5 expression was associated with down-regulation of CCR5 mRNA expression. The CC-chemokine RANTES protein and mRNA expression levels were slightly increased in CD4(+) enriched lymphocytes treated with statins. Both R5 and X4 HIV-1 were reduced for their infection of statin-treated cells; however, in cultures where statins were removed and where a decrease in CCR5 expression was observed, there was a preferential inhibition of infection with an R5 versus X4 virus.
The results indicate that the modulation of CC-chemokine receptor (CCR5) and CC-chemokine (RANTES) expression levels should be considered as contributing to the anti-viral effects of statins, preferentially inhibiting R5 viruses. This observation, in combination with the immunomodulatory activity exerted by statins, suggests they may possess more potent anti-HIV-1 activity when applied during the early stages of infection or in lowering viral transmission. Alternatively, statin treatment could be considered as a way to modulate immune induction such as during vaccination protocols.
他汀类药物先前已被证明可通过调节 Rho GTPase 活性和细胞表面脂质筏形成，以及破坏 LFA-1 整合到病毒颗粒中，从而减少人类免疫缺陷病毒 1 型（HIV-1）的体外感染。
在这里，我们证明用洛伐他汀（Lov）、美伐他汀（Mev）和辛伐他汀（分别为激活和非激活的 Sim(A)和 Sim(N)）处理富含 CD4+淋巴细胞群体可以降低 CC-趋化因子受体 CCR5 的细胞表面表达（Sim(A)和 Lov 时 P<0.01）。降低的 CCR5 表达与 CCR5 mRNA 表达下调有关。用他汀类药物处理的 CD4+富集淋巴细胞中，CC-趋化因子 RANTES 蛋白和 mRNA 表达水平略有增加。两种 R5 和 X4 HIV-1 的感染均减少了他汀类药物处理的细胞；然而，在去除他汀类药物且观察到 CCR5 表达下降的培养物中，R5 对 X4 病毒的感染存在优先抑制。
结果表明，CC-趋化因子受体（CCR5）和 CC-趋化因子（RANTES）表达水平的调节应被视为他汀类药物抗病毒作用的贡献因素，优先抑制 R5 病毒。这一观察结果，结合他汀类药物发挥的免疫调节活性，表明它们在感染早期或降低病毒传播时应用时可能具有更强的抗 HIV-1 活性。或者，可以考虑他汀类药物治疗作为调节免疫诱导的一种方式，例如在疫苗接种方案中。
