INTRACELLULAR VIRUS NEUTRALIZATION BY IGA ANTIBODIES IN HOST DEFENSE IN VIVO

IGA 抗体在体内宿主防御中中和细胞内病毒

• 批准号: 6099833
• 负责人: MARY B MAZANEC
• 金额: $ 12.44万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6099833
• 关键词: SCID mouse; antiantibody; antiviral antibody; dimer; disease /disorder model; host organism interaction; immunoglobulin A; intracellular; laboratory mouse; liver cells; microorganism immunology; murine hepatitis virus; neutralizing antibody; parainfluenza virus type 1; respiratory epithelium; respiratory virus; virus antigen; virus diseases

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.

传统上，粘膜 IgA 被视为免疫屏障，可预防 病毒粘附在上皮上。 因此，对病毒的抵抗力 感染与病毒特异性 IgA 的存在最相关 粘膜分泌物中的抗体。 最近的研究采用体外 极化上皮单层系统表明聚合 IgA， 因为它是通过聚合免疫球蛋白在细胞中运输的 受体，可与细胞内病毒蛋白结合，有效预防 病毒复制。 本提案的重点是调查 小鼠体内聚合 IgA 对病毒的细胞内中和 模型。 其中包括三个具体目标。 最初，使用单克隆 针对仙台病毒结构蛋白的抗体，我们将 检查 IgA 中断小鼠体内病毒复制的能力 体内气管上皮细胞。 其次，由于小鼠肝细胞 表达聚合免疫球蛋白受体并转运聚合 IgA 从血液入档，我们将研究IgA单克隆的能力 针对小鼠肝炎病毒的抗体可干扰病毒 在体内肝细胞内复制。 最后，我们将调查 抗原特异性对抗原特异性的影响 IgA 中和气管内病毒的细胞内位置 小鼠模型体内的上皮细胞和肝细胞。 这些研究产生的信息应该有助于我们 了解细胞内抗体中和现象 病毒和开发安全、有效的抗病毒免疫 程序。