Department of Virology I, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
J Gen Virol. 2010 Jan;91(Pt 1):103-11. doi: 10.1099/vir.0.014829-0. Epub 2009 Sep 23.
Sub-neutralizing concentrations of antibody to dengue virus (DENV) enhance DENV infection of Fc gamma receptor-expressing cells. This phenomenon, referred to as antibody-dependent enhancement (ADE), has been hypothesized to be responsible for the severe form of DENV infection, including dengue haemorrhagic fever and dengue shock syndrome. To analyse further the mechanisms of ADE in vitro, this study introduced a series of cytoplasmic mutants into human Fc gammaRIIA. The mutated Fc gammaRIIA was then expressed on COS-7 cells to see whether these mutants could enhance DENV infection. Wild-type Fc gammaRIIA enhanced DENV infection, consistent with previous reports using Fc gammaR-positive monocytes. Disruption of the immune tyrosine activation motif (ITAM) in the cytoplasmic domain of Fc gammaRIIA or removing the sequences between the two ITAM regions eliminated ADE. These findings suggest that the specific structure of the Fc gammaRIIA cytoplasmic domain is essential for the ability of Fc gammaRIIA to mediate ADE.
抗体对登革热病毒（DENV）的亚中和浓度增强了 Fcγ受体表达细胞的 DENV 感染。这种现象被称为抗体依赖性增强（ADE），被认为是导致 DENV 感染严重形式的原因，包括登革出血热和登革休克综合征。为了进一步分析体外 ADE 的机制，本研究将一系列细胞质突变体引入人 FcγRIIA。然后将突变的 FcγRIIA 表达在 COS-7 细胞上，以观察这些突变体是否可以增强 DENV 感染。野生型 FcγRIIA 增强了 DENV 感染，与先前使用 FcγR 阳性单核细胞的报道一致。FcγRIIA 细胞质域中免疫酪氨酸激活基序（ITAM）的破坏或去除两个 ITAM 区域之间的序列消除了 ADE。这些发现表明 FcγRIIA 细胞质域的特定结构对于 FcγRIIA 介导 ADE 的能力是必不可少的。
