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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Ligation of Fc gamma receptor MB inhibits antibody-dependent enhancement of dengue virus infection
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Ligation of Fc gamma receptor MB inhibits antibody-dependent enhancement of dengue virus infection

机译：Fcγ受体MB的连接抑制​​登革热病毒感染的抗体依赖性增强

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摘要

The interaction of antibodies, dengue virus (DENV), and monocytes can result in either immunity or enhanced virus infection. These opposing outcomes of dengue antibodies have hampered dengue vaccine development Recent studies have shown that antibodies neutralize DENV by either preventing virus attachment to cellular receptors or inhibiting viral fusion intracellularly. However, whether the antibody blocks attachment or fusion, the resulting immune complexes are expected to be phagocytosed by Fc gamma receptor (FcyR)-bearing cells and cleared from circulation. This suggests that only antibodies that are able to block fusion intracellularly would be able to neutralize DENV upon FcyR-mediated uptake by monocytes whereas other antibodies would have resulted in enhancement of DENV replication. Using convalescent sera from dengue patients, we observed that neutralization of the homologous serotypes occurred despite FcyR-mediated uptake. However, FcyR-mediated uptake appeared to be inhibited when neutralized heterologous DENV serotypes were used instead. We demonstrate that this inhibition occurred through the formation of viral aggregates by antibodies in a concentration-dependent manner. Aggregation of viruses enabled antibodies to cross-link the inhibitory FcyRIIB, which is expressed at low levels but which inhibits FcyR-mediated phagocytosis and hence prevents antibody-dependent enhancement of DENV infection in monocytes.
机译：抗体，登革热病毒（DENV）和单核细胞的相互作用可导致免疫力增强或病毒感染增加。登革热抗体的这些相反结果阻碍了登革热疫苗的开发。最近的研究表明，抗体可通过防止病毒附着于细胞受体或抑制细胞内病毒融合来中和DENV。但是，无论抗体是阻断结合还是融合，产生的免疫复合物都有望被带有Fcγ受体（FcγR）的细胞吞噬并从循环中清除。这表明，只有能够阻断细胞内融合的抗体才能在单核细胞通过FcyR介导的摄取后中和DENV，而其他抗体将导致DENV复制的增强。使用登革热患者的恢复期血清，我们观察到尽管FcyR介导的摄取，同源血清型仍被中和。然而，当使用中和的异源DENV血清型代替时，FcγR介导的摄取似乎被抑制。我们证明了这种抑制是通过抗体以浓度依赖性方式通过病毒聚集体的形成而发生的。病毒的聚集使抗体能够交联抑制性FcyRIIB，该FcyRIIB以低水平表达，但抑制FcyR介导的吞噬作用，因此阻止了单核细胞中DENV感染的抗体依赖性增强。

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    Kuan Rong Chan; Summer Li-Xin Zhang; Hwee Cheng Tan; Ying Kai Chan; Angelia Chow; Angeline Pei Chiew Lim; Subhash G. Vasudevan; Brendon J. Hanson; Eng Eong Ooi;

  • 作者单位

    National University of Singapore Graduate School, National University of Singapore, Singapore 117456;

    Defence Science Organization National Laboratories, Singapore 117510;

    Duke-National University of Singapore Graduate Medical School, Singapore 169854;

    Defence Science Organization National Laboratories, Singapore 117510;

    Duke-National University of Singapore Graduate Medical School, Singapore 169854;

    Defence Science Organization National Laboratories, Singapore 117510;

    Duke-National University of Singapore Graduate Medical School, Singapore 169854;

    Defence Science Organization National Laboratories, Singapore 117510;

    Defence Science Organization National Laboratories, Singapore 117510,Duke-National University of Singapore Graduate Medical School, Singapore 169854;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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