Caprine arthritis-encephalitis virus (CAEV) is a macrophage-tropic lentivirus that causes a persistent life-long infection in goats. The biochemical and genetic structure, replication in host cells, antigenic variation in the envelope glycoprotein and the capacity to evade host immune responses of the CAEV are very similar to HIV. However, the cell adherence, virus penetration and pathogenic mechanisms of CAEV have not been fully elucidated. The CAEV-induced disease in goats serves as a model not only to study the pathogenesis of lentiviruses but allows to study efficacy of novel vaccine candidates, cytokines and adjuvants. Development of new and improve vaccines will rely on a sophisticated understanding of the molecular biology, mechanisms of pathogenesis and interactions with immune system particular to a given pathogen. Realizing this fact, we wish to study the efficacy of mucosal immunization using microencapsulated DNA antigen (plasmid expressing gp135 covalently linked to poly-DL-lactide co- glycolide; PLG) that may provide strong, long lasting circulating and mucosal antibody responses, long term immunological memory as well as proliferative and cytolytic (cell-mediated immune) responses. We also propose to produce recombinant caprin interleukin-12 (IL-12) and study its efficacy as an immunoadjuvant in lentiviral infection in the goat. In a preliminary study, we have observed the capability of beta-chemokines, RANTES and MIP-1alpha to down regulate the replication of CAEV in vitro. These beta-chemokines are produced predominantly by CD8+ T cells and may block CAEV replication by occupying the newly identified CC-CKR5 receptor which appears to be necessary for the efficient entry of the predominantly macrophage-tropic lentivirus into its target cells. However, beta- chemokines may not completely account for the inhibition of CAEV replication. The full spectrum of cytokines involved in CD8+ T-cell mediated, non-cytolytic suppression of CAEV needs further investigation. In the proposed study, using RT-PCR methods, we will determine the expression of IL-12, IL-16 and beta-chemokines in appropriate cells from goats showing: clinical symptoms, infected by asymptomatic, exposed but uninfected, and control uninfected goats. The findings from the proposed study may suggest fundamentally new concepts regarding the CAEV entry, pathogenesis and prophylactic measures.
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