Repression of BK virus infection of human renal proximal tubular epithelial cells by pravastatin.
BACKGROUND
BK virus (BKV), a human polyomavirus, causes BKV nephritis, which often leads to graft loss after renal transplantation. Currently, the only efficient therapy against BKV nephritis seems to be a reduction or change of immunosuppressive agents, but this may increase the inherent risk of rejection. Here, we report the ability of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitor (statin), which is routinely used to treat hypercholesterolemia, to repress BKV entry pathways in human renal proximal tubular epithelial cells (HRPTEC) and, correspondently, prevent BKV infection.


METHODS
HRPTEC were co-incubated with BKV and pravastatin. Then the percentage of HRPTEC infected with BKV by immunofluorescent analysis and large T-antigen expression which suggested BKV infection by Western blots was assessed in the absence and presence of pravastatin. The distribution of purified and labeled BKV particles in the presence and absence of pravastatin was also investigated.


RESULTS
Both the percentage of BKV infected cells and the large T-antigen expression were significantly decreased in HRPTEC pretreated and co-incubated with pravastatin. However, when pravastatin was added 72 hr after BKV infection it failed to decrease percentage of BKV infected cells. It is likely, that pravastatin's inhibitory effect is explained by depletion of caveolin-1, a critical element of caveolae. BKV enters HRPTEC by caveolar-mediated endocytosis. We provide evidence that pravastatin dramatically decreased caveolin-1 expression in HRPTEC and interfered with internalization of labeled BKV particles.


CONCLUSIONS
Our data suggest that pravastatin, acting through depletion of caveolin-1, prevented caveolar-dependent BKV internalization and repressed BKV infection of HRPTEC.
Moriyama
Takahito
T
Division of Nephrology and Kidney Disease Center, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Sorokin
Andrey
A
D001739:BK Virus / Q000187:drug effects*; D051242:Caveolin 1 / Q000037:antagonists & inhibitors / Q000187:drug effects; D004847:Epithelial Cells / Q000821:virology*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000821:virology*; D027601:Polyomavirus Infections / Q000517:prevention & control; D017035:Pravastatin / Q000494:pharmacology*; D014412:Tumor Virus Infections / Q000517:prevention & control
C495540:CAV1 protein, human; D051242:Caveolin 1; D017035:Pravastatin