IN-VIVO AND IN-VIVO INFECTION WITH 2 DIFFERENT MOLECULAR CLONES OF VISNA-VIRUS

The behavior of two genetically different molecular clones of visna vi rus KV1772-kv72/67 and LV1-1KS1 was compared in vivo and in vitro. On intracerebral inoculation, clone KV1772-kv72/67 induced a similar resp onse in five sheep as has already been reported with neurovirulent der ivates of visna virus. Virus was frequently isolated from blood, cereb rospinal fluid (CSF), and lymphoid organs and induced characteristic c entral nervous system (CNS) lesions, A strong humoral immune response was detected by ELISA, immunoblotting, and neutralization. Six sheep i nfected with clone LV1-1KS1 showed a completely different picture. No virus could he isolated from blood or CSF during 6 months of infection . At sacrifice all organs were virus-negative except the CNS of one sh eep. None of the six sheep developed significant neutralizing antibodi es and only low titer antibodies were detected by ELISA and immunoblot ting. Minimal CNS lesions were present in one sheep. The molecular clo nes were also tested in sheep choroid plexus cells (SCP) and macrophag es. In macrophages LV1-1KS1 replicated to a significantly lower titer but induced much more cell fusion than KV1772-kv72/67. The clones repl icated equally well in SCP cells. Thus, these molecular clones of visn a virus, which differ only by 1% in nucleotide sequence, showed a prof ound difference in replication and pathogenicity both in vitro and in vivo. These results can he used to map viral genetic determinants impo rtant for host-lentivirus interactions. (C) 1997 Academic Press.