Transgenic mouse core

抽象-核心A，Bournazos 免疫球蛋白抗体在体内介导生物效应的能力，如对病毒感染的保护 从它的两面性出发。抗体的Fab区识别病毒尖峰上的表位，并可能干扰 与病毒结合到靶细胞，而Fc结构域通过 与效应白细胞表达的Fcγ受体(FcγR)的特异性相互作用。几种传染性疾病的研究 病原体已经表明，Fc-FcγR相互作用具有调节广谱对立的能力 功能-从病毒调理和清除受感染的细胞(保护性)到增强病毒感染和 疾病严重程度(致病)。了解免疫球蛋白抗体介导免疫球蛋白的确切机制 保护或致病功能需要使用定义明确的活体实验系统，这些系统反映 参与免疫反应的效应白细胞的独特复杂性。事实上，尽管是在体外 使用细胞系或初级效应细胞的检测代表了公认的表征 关于免疫球蛋白抗体的功能，这类检测提供的信息有限，说明了 在感染期间或接种疫苗时提高人体免疫力。我们将提供一个核心，它将维护 鉴定一系列基因工程人源化小鼠品系，并将其分发给该中心 支持关于抗黄病毒致病活性特征的拟议研究的调查人员 增加登革热易感性的抗体以及保护性抗病毒药物的评价 中和抗乙肝病毒抗体的功能。通过特定的关键免疫信号的缺失 与代表自然病毒宿主细胞类型的人类原代细胞的途径或重组，这些 转基因小鼠品系支持黄病毒和肝炎病毒在体内的感染和复制， 从而便于研究病毒疾病的发病机制以及分子特征 病毒感染过程中影响免疫球蛋白抗体活性的机制

ABSTRACT – Core A, Bournazos The ability of an IgG antibody to mediate biological effects in vivo, such as protection from viral infection, results from its bispecific nature. The Fab region of an antibody recognizes epitopes on the viral spike and may interfere with virus binding to target cells, while the Fc domain mediates diverse immunomodulatory activities through specific interactions with Fcγ receptors (FcγRs) expressed by effector leukocytes. Studies on several infectious pathogens have shown that Fc-FcγR interactions have the capacity to mediate a wide spectrum of opposing functions – from viral opsonization and clearance of infected cells (protective) to enhanced viral infection and disease severity (pathogenic). Understanding the precise mechanisms by which IgG antibodies mediate protective or pathogenic functions necessitates the use of well-defined in vivo experimental systems that reflect the unique complexity of effector leukocytes that participate in an immune response. Indeed, although in vitro assays using cell lines or primary effector cells represent well-established approaches for characterizing the function of IgG antibodies, such assays provide limited information on the precise molecular mechanisms that drive human immunity during infection or upon vaccination. We will provide a Core that will maintain, characterize, and distribute a series of genetically-engineered humanized mouse strains to the Center investigators in support of the proposed studies on the characterization of the pathogenic activity of anti-flavivirus antibodies that confer susceptibility to dengue disease, as well as on the evaluation of the protective antiviral function of neutralizing antibodies against hepatitis B viruses. Through specific deletions of key immune signaling pathways or reconstitution with human primary cells that represent the natural viral host cell type, these engineered mouse strains support the infection and replication of flaviviruses and hepatitis viruses in vivo, thereby facilitating the study of viral disease pathogenesis, as well as the characterization of the molecular mechanisms that contribute to the IgG antibody activity during viral infection.