INTRACELLULAR VIRUS NEUTRALIZATION BY IGA ANTIBODIES IN HOST DEFENSE IN VIVO

传统上，粘膜伊加一直被视为预防免疫缺陷的免疫屏障。 病毒对上皮细胞的粘附。 因此，对病毒的抗性 感染与病毒特异性伊加的存在最相关 粘膜分泌物中的抗体。 最近的研究采用体外 极化的上皮单层系统已经表明， 因为它是由多聚免疫球蛋白通过细胞转运的 受体，可以结合细胞内的病毒蛋白，有效地防止 病毒复制 这份提案的重点是调查 多聚伊加对病毒细胞内中和作用 模型 包括三个具体目标。 最初，使用单克隆 针对仙台病毒结构蛋白的抗体， 检测伊加阻断小鼠体内病毒复制的能力 气管上皮细胞。 其次，由于小鼠肝细胞 表达多聚免疫球蛋白受体和转运多聚伊加 从血液进入文件，我们将研究伊加单克隆抗体的能力， 针对小鼠肝炎病毒的抗体， 在肝细胞内的体内复制。 最后，我们将调查 抗原特异性的影响，与容易和对 伊加中和两个气管内病毒的细胞内位置 上皮细胞和肝细胞。 这些研究所产生的信息应有助于我们 对细胞内抗体中和现象的理解 以及发展安全、有效的抗病毒免疫 程序.

Traditionally, mucosal IgA has been viewed as an immune barrier to prevent the adherence of viruses to epithelium. As such, resistance to viral infections best correlates with the presence of viral specific IgA antibodies in mucosal secretions. Recent studies employing an in vitro polarized epithelial monolayer system have suggested that polymeric IgA, as it is transported through the cell by the polymeric immunoglobulin receptor, can bind to intracellular viral proteins, effectively preventing viral replication. The focus of this proposal is to investigate intracellular neutralization of virus by polymeric IgA in vivo in murine models. Three specific aims are included. Initially, using monoclonal antibodies against the structural proteins of Sendai virus, we will examine the ability of IgA interrupt viral replication within murine tracheal epithelial cells in vivo. Secondly, since murine hepatocytes express the polymeric immunoglobulin receptor and transport polymeric IgA from the blood into the file, we will study the ability of IgA monoclonal antibodies directed against mouse hepatitis virus to interfere with viral replication in vivo within hepatocytes. Finally, we will investigate the effect of antigenic specificity on the ease with which and on the intracellular location where IgA neutralizes virus within both tracheal epithelial cells and hepatocytes in vivo in the murine models. Information generated by these studies should contribute to our understanding of the phenomenon of intracellular antibody neutralization of virus and to the development of safe, effective antiviral immunization procedures.