statins disrupt ccr5 and rantes expression levels in cd4+ t lymphocytes in vitro and preferentially decrease infection of r5 versus x4 hiv-1他汀类药物阻断ccr5和咆哮表达cd4 + t淋巴细胞在体外和优先减少r5和x4 hiv - 1的感染.pdf

Statins Disrupt CCR5 and RANTES Expression Levels in CD4+ T Lymphocytes In Vitro and Preferentially Decrease Infection of R5 Versus X4 HIV-1 1¤a 1 1¤b 1 2¤c Alexey A. Nabatov , Georgios Pollakis , Thomas Linnemann , William A. Paxton *, Michel P. de Baar 1 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, 2 Primagen, Amsterdam, The Netherlands Background. 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. Principle Findings. 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. Conclusions. The results indicate that the modulation of CC-chemokine receptor (CCR5) and CC-chemokine (RANTES) expression levels should be considered