EFFECT OF CYCLOSPORINE-A ON THE REPLICATION CYCLE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 DERIVED FROM H9 AND MOLT-4 PRODUCER CELLS

The effect of cyclosporin A (CsA) on the replication of human immunode ficiency virus type 1 (HIV-1) was studied. CsA treatment inhibited vir us production in chronically infected H9 and Molt-4 cells. CsA treatme nt of HeLaCD4/LTR/beta-gal cells or extracellular viruses also inhibit ed infection (IC50 1 mu g/ml). The intracellular CsA-binding molecule cyclophilin A was detected in HIV-1 derived from chronically infected H9 cells, but it was present at a substantially lower level in HIV-1 d erived from chronically infected Molt-4 cells. The low level of cyclop hilin A in viral particles derived from Molt-4 cells correlated well w ith their substantially lower infectivity as assayed on HeLaCD4-LTR/be ta-gal cells. CsA treatment of infected cells showed a dose-dependent reduction of cyclophilin A incorporation into virions; the amount of c yclophilin A incorporation was found to be dependent on the producer c ell type.