Priming with tat-Deleted Caprine Arthritis Encephalitis Virus (CAEV) Proviral DNA or Live Virus Protects Goats from Challenge with Pathogenic CAEV

摘要

We previously reported that infection of goats with caprine arthritis encephalitis virus (CAEV) tat− proviral DNA or virus results in persistent infection, since the animals seroconverted and direct virus isolation from cultures of blood-derived macrophages was positive. In this study we wanted to determine whether goats injected with CAEV tat− proviral DNA or virus were protected against challenge with the pathogenic homologous virus and to investigate whether CAEV tat− was still pathogenic. All animals injected with CAEV tat− became infected as indicated by seroconversion and virus isolation. Challenge at 8 or 9 months postinfection demonstrated protection in four of four animals injected with CAEV tat− but did not in three of three mock-inoculated challenged goats. Challenge virus was undetectable in the blood macrophages of protected animals during a period of 6 or 10 months postchallenge. In two of four protected animals, however, we were able to detect the challenge wild-type virus by reverse transcriptase PCR on RNA directly extracted from synovial membrane cells surrounding the inoculation site. This result suggests that protection was achieved without complete sterilizing immunity. Animals injected with CAEV tat− and mock challenged developed inflammatory lesions in the joints, although these lesions were not as severe as those in CAEV wild-type-injected goats. These results confirm the dispensable role of Tat in CAEV replication in vivo for the establishment of infection and pathogenesis and demonstrate in another lentivirus infection model the efficacy of live attenuated viruses to induce resistance to superinfection.