NEUROINVASION BY OVINE LENTIVIRUS IN INFECTED SHEEP MEDIATED BY INFLAMMATORY CELLS ASSOCIATED WITH EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS

Maedi Visna Virus (MVV) is a prototypic lentivirus that causes infecti on only in cells of macrophage lineage, unlike the primate lentiviruse s which infect both CD4(+) T lymphocytes and macrophages, In primates, the earliest viral invasion is associated with the ability of the vir us to infect and activate T cells which: convey virus to the brain, In fected monocytes in blood rarely cause CNS infection in absence of act ivation CD4(+) T cells. In the face of lack of infection or activation of T cells by MVV in sheep, the question arises, how does MVV gain ac cess to the brain to cause the classical lesions of visna? In previous studies an experimental induction of visna, sheep were inoculated wit h virus directly in the brain, In this study, we asked whether neuroin vasion by MVV would occur if sheep were inoculated with virus in a non -neural site, Nine sheep were inoculated intratracheally and all devel oped systemic infection when examined 3 weeks later, At this time, fiv e were injected intramuscularly with brain white matter homogenized in Freund's complete adjuvant: to induce EAE, None of the four animals i noculated with virus alone developed CNS infection despite typical len tiviral infection in lungs, lymphoid tissues and blood-borne mononucle ar cells. In contrast, all five of the sheep injected with brain homog enate developed infection in the brain. Virus was produced by macropha ges associated with the EAE lesions, This study illustrated that both activated T cells specific for antigen in the CNS and infected macroph ages are essential for lentivirus neuropathogenesis.