Kennedy-Stoskopf S, Zink M C, Jolly P E, Narayan O
Johns Hopkins University, School of Medicine, Division of Comparative Medicine, Baltimore, Maryland.
Rheum Dis Clin North Am. 1987 Aug;13(2):235-47.
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.
慢病毒是外源性、非致癌性逆转录病毒，可在单核细胞和巨噬细胞中引起持续性感染。绵羊和山羊这类感染的临床表现之一是缓慢进展的关节炎，主要累及成年动物的腕关节。最初，临床疾病表现为滑膜炎；随着炎症加剧和进展，滑膜炎会发展至累及周围结缔组织和骨结构。炎症细胞包括巨噬细胞、淋巴细胞和浆细胞。巨噬细胞和单核细胞是唯一被病毒感染的细胞，在发炎的关节中，它们可能占滑液中细胞的50%。然而，这些细胞中只有少数被感染。在滑液中，细胞毒性T淋巴细胞比辅助性T淋巴细胞占优势。目前尚不清楚这些细胞在疾病发病机制中的作用。这些慢病毒引起疾病的发病机制与动物单核细胞 - 巨噬细胞的感染有关。这一事件以及病毒特异性因素使宿主无法清除病毒。尽管病毒持续存在，但在感染动物体内，病毒复制始终维持在严格受限的水平。这是通过调节单核细胞成熟的因素实现的。基本上，感染在单核细胞及其前体细胞中处于潜伏状态，随着细胞成熟，感染变得更具生产性。成熟的被感染巨噬细胞在其细胞表面呈现一部分它合成的病毒蛋白，这些病毒蛋白与II类主要组织相容性复合体抗原紧密结合。淋巴细胞与这种细胞发生反应并产生干扰素。这种淋巴因子诱导Ia抗原的进一步表达。Ia表达的这种反馈回路，连同病毒的持续存在，使巨噬细胞维持在持续的抗原呈递状态。这形成了炎症状态的触发因素，最终导致关节中出现退行性病变。
