INHIBITION OF VACCINIA VIRUS-REPLICATION BY CYCLOSPORINE-A ANALOGS CORRELATES WITH THEIR AFFINITY FOR CELLULAR CYCLOPHILINS

The mechanism by which cyclosporin A (CsA) inhibits vaccinia virus (VV ) replication is still unclear. The present study addresses the questi on of whether CsA-binding proteins named cyclophilins (Cyps) are invol ved in the anti-VV activity of CsA. Six CsA analogues were analysed, a nd their affinity for Cyps in W-infected BSC-40 cells and their potenc y as inhibitors of VV replication were evaluated. It was demonstrated that analogues with strong Cyp-binding activity, such as CsC, CsG and [MeAla(6)]CsA, also exhibit a strong antiviral effect. In contrast, dr ugs with low ([MeBm(2)t(1)]CsA and CsH) or no ([MeLeu(11)]CsA) affinit y for Cyps show poor or no antiviral activity. The data obtained sugge st a correlation between the ability of CsA to block VV replication an d Cyp binding activity, and indicate the involvement of Cyps in the VV replicative cycle. they also suggest that the anti-VV action of CsA m ay occur by a pathway distinct from that involved in the immunosuppres sive effect of the drug.