Kennedy-Stoskopf S, Narayan O
J Virol. 1986 Jul;59(1):37-44. doi: 10.1128/JVI.59.1.37-44.1986.
Lentiviruses are nononcogenic retroviruses that cause persistent infections and slowly progressive diseases. Visna virus, a lentivirus of sheep, persists in cells of the macrophage lineage despite the presence of neutralizing antibodies in the animal. These antibodies are measured by prevention of virus replication in sheep fibroblast cell cultures. In this study we have compared the antiviral properties of the antibodies in sheep fibroblast and macrophage cell cultures, the latter being more relevant to infection in the animal. Using infectivity assays, binding of radiolabeled virus to cell membranes, cellular processing of labeled virus into acid-precipitable and acid-soluble components, and in situ hybridization of viral nucleic acid, we show that the antibodies prevented virus replication in both fibroblasts and macrophages. However, the site of neutralization differed between the two cell types. In fibroblasts, the site of virus neutralization was at the cell membrane, when the antibodies prevented virus attachment. In macrophages, virus incubated with the antibodies was phagocytized rapidly, followed by uncoating of the virions. However, virus RNA was not transcribed. Despite this ability of the antibodies to abort virus replication in macrophages, the kinetics of binding of the antibodies to the virus was much slower than the binding of virus to the macrophages. Therefore, persistent virus replication in immune sheep may be the result of virus spreading from macrophage to macrophage before the agent can be neutralized by antibodies in the plasma.
慢病毒是一种非致癌性逆转录病毒，可引起持续性感染和缓慢进展性疾病。维斯纳病毒是绵羊的一种慢病毒，尽管动物体内存在中和抗体，但它仍能在巨噬细胞系的细胞中持续存在。这些抗体通过在绵羊成纤维细胞培养物中阻止病毒复制来进行检测。在本研究中，我们比较了绵羊成纤维细胞和巨噬细胞培养物中抗体的抗病毒特性，后者与动物体内的感染更为相关。通过感染性测定、放射性标记病毒与细胞膜的结合、标记病毒在细胞内加工成酸沉淀和酸溶性成分以及病毒核酸的原位杂交，我们发现抗体在成纤维细胞和巨噬细胞中均能阻止病毒复制。然而，两种细胞类型的中和位点有所不同。在成纤维细胞中，病毒中和位点在细胞膜，此时抗体阻止病毒附着。在巨噬细胞中，与抗体孵育的病毒会迅速被吞噬，随后病毒粒子脱壳。然而，病毒RNA并未转录。尽管抗体有能力在巨噬细胞中中止病毒复制，但抗体与病毒结合的动力学比病毒与巨噬细胞结合的动力学要慢得多。因此，免疫绵羊中病毒的持续复制可能是由于在病毒被血浆中的抗体中和之前，病毒从一个巨噬细胞传播到另一个巨噬细胞的结果。
