Key Laboratory of Animal Immunology of the Ministry of Agriculture, Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou, China.
PLoS One. 2011;6(12):e28721. doi: 10.1371/journal.pone.0028721. Epub 2011 Dec 29.
Antibody-dependent enhancement (ADE) of virus infection caused by the uptake of virus-antibody complexes by FcγRs is a significant obstacle to the development of effective vaccines to control certain human and animal viral diseases. The activation FcγRs, including FcγRI and FcγRIIa have been shown to mediate ADE infection of virus. In the present paper, we showed that pocine FcγRIIb, an inhibitory FcγR, mediates ADE of PRRSV infection. Stable Marc-145 cell lines expressing poFcγRIIb (Marc-poFcγRII) were established. The relative yield of progeny virus was significantly increased in the presence of sub-neutralization anti-PRRSV antibody. The Fab fragment and normal porcine sera had no effect. Anti-poFcγRII antibody inhibited the enhancement of infection when cells were infected in the presence of anti-PRRSV antibody, but not when cells were infected in the absence of antibody. These results indicate that enhancement of infection in these cells by anti-PRRSV virus antibody is FcγRII-mediated. Identification of the inhibitory FcγR mediating ADE infection should expand our understanding of the mechanisms of pathogenesis for a broad range of infectious diseases and may open many approaches for improvements to the treatment and prevention of such diseases.
抗体依赖的增强（ADE）作用是指病毒-抗体复合物通过 FcγRs 被内吞从而导致的病毒感染增强作用，这是开发有效疫苗以控制某些人类和动物病毒病的重大障碍。已有研究表明，激活型 FcγRs（包括 FcγRI 和 FcγRIIa）可介导病毒的 ADE 感染。在本研究中，我们发现猪 FcγRIIb（一种抑制型 FcγR）介导了 PRRSV 的 ADE 感染。建立了稳定表达猪 FcγRIIb（Marc-poFcγRII）的 Marc-145 细胞系。在存在亚中和效价抗 PRRSV 抗体的情况下，病毒的复制产量显著增加。Fab 片段和正常猪血清没有影响。当细胞在存在抗 PRRSV 抗体的情况下感染时，抗猪 FcγRII 抗体抑制了感染的增强，但当细胞在不存在抗体的情况下感染时，没有抑制作用。这些结果表明，这些细胞中抗 PRRSV 病毒抗体介导的感染增强作用是通过 FcγRII 介导的。鉴定出介导 ADE 感染的抑制型 FcγR，应能扩展我们对广泛的传染病发病机制的理解，并可能为改善此类疾病的治疗和预防提供多种方法。
