REQUIREMENT OF CAPRINE ARTHRITIS-ENCEPHALITIS VIRUS VIF GENE FOR IN-VIVO REPLICATION

Replication of vif- caprine arthritis encephalitis virus (CAEV) is hig hly attenuated in primary goat synovial membrane cells and blood-deriv ed macrophages compared to the wild-type (wt) virus. We investigated t he requirement for CAEV Vif for in vivo replication and pathogenicity in goats by intra-articular injection of either infectious proviral DN A or viral supernatants. Wild-type CAEV DNA or virus inoculation induc ed persistent infection resulting in severe inflammatory arthritic les ions in the joints. We were unable to detect any sign of virus replica tion in vif- CAEV DNA inoculated goats, while vif- CAN virus inoculati on resulted in the seroconversion of the goats. However, virus isolati on and RT-PCR analyses on blood-derived macrophage cultures remained n egative throughout the experiment as well as in joint or lymphoid tiss ues taken at necropsy. No pathologic lesions could be observed in join t tissue sections examined at necropsy. Goats inoculated with the vif- virus demonstrated no protection against a pathogenic virus challenge . These results demonstrate that CAEV Vif is absolutely required for e fficient in vivo virus replication and pathogenicity and provide addit ional evidence that live attenuated lentiviruses have to establish a p ersistent infection to induce efficient protective immunity. (C) 1996 Academic Press, Inc.