Simvastatin Induces Nucleoporins Rae1/ mrnp41 and Nup98 via a STAT-1 Pathway, and Modulates Vesicular Stomatitis Virus Replication

Introduction. Statins, the cholesterol-lowering drugs, are known to exert pleiotropic effects that include inhibition of viruses such as HIV, HCV, polio and influenza-A. VSV is the prototype virus for take-over of nuclear pore complex (NPC) function via blockage of mRNA export; an effect antagonized by upregulation of Rae-1 and Nup98. Both nucleoporins are required for mRNA export and for the infection/replication of VSV, influenza A and polio viruses. Case Presentation. To determine a possible effect of statins on the NPC and on VSV replication, we investigated the effects of statins on VSV replication and on the expression of Rae1 and Nup98. Here we show for the first time that Simvastatin inhibits VSV replication and up-regulates both Nup98 and Rae1, in a concentration and STAT1- dependent manner. Simvastatin reversed VSV mRNA export block, a typical cytopathic effect of VSV on infected cells, and inhibited VSV replication. Deviation From the Expected. A low concentration of Simvastatin (0.125μM) and Pravastatin (0.1-4 μM) induced increases in VSV proteins and titers. Discussion. Here we reported that Simvastatin altered the replication of VSV and reduced the inhibition of gene expression induced by VSV. Conclusion. When drugs are directed towards cellular components, they could exert broad-range antiviral therapy. Simvastatin may be one example of drugs that modulate host factors needed for viral replication. Furthermore, modulation of antiviral nucleoporins might be an essential strategy of defense for both innate and adaptive immunity. Grant. The present studies were funded by NSU Chancellor's Faculty Research & Development Grant No. 335508.