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.
Salvatori
D
D
Dipartimento di Scienze Veterinarie, Universitià di Camerino, Matelica, Italy.
Vincenzetti
S
S
Maury
G
G
Gosselin
G
G
Gaubert
G
G
Vita
A
A
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003562:Cytidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003588:Cytopathogenic Effect, Viral; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D012756:Sheep; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects*; D014790:Visna-maedi virus / Q000187:drug effects* / Q000502:physiology; D016047:Zalcitabine / Q000494:pharmacology
D019380:Anti-HIV Agents; D003562:Cytidine; D016047:Zalcitabine