Virology-CIET, Faculty of Microbiology, University of Costa Rica, 11501-2060, San José, Costa Rica.
Semin Immunopathol. 2014 Nov;36(6):627-40. doi: 10.1007/s00281-014-0448-2. Epub 2014 Oct 7.
The constant region of IgG antibodies mediates antiviral activities upon engaging host Fcγ receptors (FcγRs) expressed by a variety of immune cells, such as antibody-dependent cellullar cytotoxcity (ADCC) executed by natural killer (NK)cells. Human cytomegalovirus (HCMV) is unique among viruses by encoding also an array of several Fcγ-binding glycoproteins with cell surface disposition and concomitant incorporation into the virion. Evidence is increasing that the virus-encoded Fcγ receptors differ in their Fcγ binding mode but effectively operate as adversaries of host FcγRs since they are able to prevent IgG-mediated triggering of activating host FcγRs, i.e., FcγRI, FcγRIIA, and FcγRIIIA. Here we discuss virus-encoded FcγRs as the first known HCMV inhibitors of IgG-mediated immunity which could account for the limited efficacy of HCMV hyperimmune globulin in clinical settings. A better understanding of their molecular mode of action opens up new perspectives for improving IgG therapies against HCMV disease.
免疫球蛋白 G（IgG）抗体的恒定区通过与多种免疫细胞表达的宿主 Fcγ 受体（FcγRs）结合，介导抗病毒活性，如自然杀伤（NK）细胞执行的抗体依赖的细胞细胞毒性（ADCC）。人巨细胞病毒（HCMV）通过编码一系列具有细胞表面分布的 Fcγ 结合糖蛋白并同时整合到病毒粒子中，在病毒中是独特的。越来越多的证据表明，病毒编码的 Fcγ 受体在 Fcγ 结合模式上存在差异，但由于它们能够阻止 IgG 介导的激活宿主 FcγRs 的触发，即 FcγRI、FcγRIIA 和 FcγRIIIA，因此实际上作为宿主 FcγRs 的拮抗剂。在这里，我们将病毒编码的 Fcγ 受体作为第一个已知的 HCMV 抑制 IgG 介导免疫的因子进行讨论，这可以解释 HCMV 高免疫球蛋白在临床环境中的有限疗效。更好地了解它们的分子作用模式为改善针对 HCMV 疾病的 IgG 治疗开辟了新的前景。
