Maedi-visna virus, a model for in vitro testing of potential anti-HIV drugs

A series of beta-D- and beta-L-cytidine analogues were evaluated for their inhibitory effect on the replication of maedi-visna virus (MVV) strains KV1772 and MV1514 cultured on sheep choroid plexus cells and the sheep chondrocyte cell line G81092, respectively. Eleven cytidine analogues were selected for the anti-viral test. Five of them belong to the family of the 2',3'-dideoxycytidine analogues, well known for their activity against human immunodeficiency virus (HIV). The others, all newly synthesized, were potential anti-viral and/or anti-leukemic agents. None of the compounds under study had a toxic effect in both anti-viral assay systems up to a 300 microM concentration. Based on the cytopathic effects (CPE), the virus replication was completely inhibited by the five 2',3'-dideoxycytidine analogues at a concentration of 50 microM, whereas the others six newly synthesized compounds induced titre reductions of 4-5 log units. The effective concentration causing 50% reduction of CPE (EC50) was of 5 microM for the five 2',3'-dideooxycytidine analogues and for beta-L-XyloFc, whereas the value of 50 microM was found for the b-L-XyloC and the four 5-azacytidine compounds tested. All these data reveal a good correlation between inhibition of MVV replication by several nucleoside cytidine analogues and their reported anti-HIV activity.