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

Abstract

A series of β- d- and β- 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 μM 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 μM, whereas the others six newly synthesized compounds induced titre reductions of 4–5 log units. The effective concentration causing 50% reduction of CPE (EC 50) was of 5 μM for the five 2′,3′-dideooxycytidine analogues and for β- l-XyloFc, whereas the value of 50 μM 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.