Lentivirus-Induced Arthritis: Chronic Disease Caused by a Covert Pathogen

Abstract

Lentiviruses are exogenous, nononcogenic retroviruses that cause persistent infections in monocytes and macrophages. Among the clinical manifestations of such infections in sheep and goats is a slowly progressive arthritis, primarily involving the carpal joints of adult animals. Initially, clinical disease begins as synovitis; this progresses to involve surrounding connective tissues and osseous structures as inflammation increases and progresses. Inflammatory cells include macrophages, lymphocytes, and plasma cells. Macrophages and monocytes are the only cells that are infected with virus and in the inflamed joint may represent 50 per cent of the cells in the synovial fluid. However, only a small number of these cells are infected. Cytotoxic T lymphocytes predominate over helper T lymphocytes in the synovial fluid. The role of these cells in the pathogenesis of disease is not currently known. The pathogenesis of disease caused by these lentiviruses is related to the infection of the monocyte-macrophage cells in the animal. This event, along with virus-specific factors, render the host incapable of eliminating the virus. Despite persistence of the virus, viral replication is maintained at a tightly restricted level at all times in the infected animal. This is achieved by factors that regulate the maturation of monocytes. Basically, the infection is latent in monocytes and its precursors and becomes more productive as the cells mature. The maturing infected macrophage presents a portion of the viral proteins that it synthesizes on its cell surface in close association with class II major histocompatibility complex antigens. Lymphocytes react with this cell and produce interferon. This lymphokine induces further expression of Ia antigens. This feedback loop of Ia expression, together with persistence of the virus, maintains macrophages in a constant state of antigen presentation. This forms the trigger for the inflammatory condition that eventually leads to the degenerative lesions seen in the joint.