Sci Transl Med ：杀死登革病毒的人源抗体

近日，新加坡和英国的科学家分离出了一种人类抗体，能够有效地消除蚊子传播的登革热病毒。登革热是登革热病毒引起、依蚊传播的一种急性传染病，病人和隐性感染者是主要传染源。临床特征为起病急骤，高热，全身肌肉、骨髓及关节痛，极度疲乏，部分患可有皮疹、出血倾向和淋巴结肿大。

登革热由登革病毒感染引起，登革病毒属B组虫媒病毒，黄病毒科黄病毒属（flavivirus）。病毒基因编码3个结构蛋白和7个非结构蛋白。3个结构蛋白分别为E蛋白、C蛋白和M蛋白。E蛋白含有中和抗原和病毒的种、属、型等特异性表位，可诱导机体产生中和抗体、血凝抑制抗体。此外，E蛋白还可能引起抗体依赖的增强感染作用（ADE）。C蛋白可能在蛋白质和RNA的相互作用中发挥作用。M蛋白与病毒感染能力的强弱有关。登革病毒可分为4个血清型，与其他B组虫媒病毒如乙型脑炎病毒可交叉免疫反应。新分离出的抗体HM14c10对1型血清有效。

研究团队招募约100名登革热患者，收集了超过20万种抗体。HM14c10抗体能在病毒感染细胞前就能杀死病毒。研究人员用分离出的抗体在小鼠上进行实验发现，它通过覆盖整个病毒表面防止其表面蛋白的变化，防止病毒感染细胞。该论文发表在Science Translational Medicine杂志上，这一发现可能有助于研究人员开发新的疗法来治疗或预防登革热病毒的感染。

doi:10.1126/scitranslmed.3003888
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The Structural Basis for Serotype-Specific Neutralization of Dengue Virus by a Human Antibody

Ee Ping Teoh1,*, Petra Kukkaro2,3,*, En Wei Teo1,*, Angeline P. C. Lim2, Tze Tong Tan1,
et al.

Dengue virus (DENV) is a mosquito-borne flavivirus that affects 2.5 billion people worldwide. There are four dengue serotypes (DENV1 to DENV4), and infection with one elicits lifelong immunity to that serotype but offers only transient protection against the other serotypes. Identification of the protective determinants of the human antibody response to DENV is a vital requirement for the design and evaluation of future preventative therapies and treatments. Here, we describe the isolation of a neutralizing antibody from a DENV1-infected patient. The human antibody 14c10 (HM14c10) binds specifically to DENV1. HM14c10 neutralizes the virus principally by blocking virus attachment; at higher concentrations, a post-attachment step can also be inhibited. In vivo studies show that the HM14c10 antibody has antiviral activity at picomolar concentrations. A 7 Å resolution cryoelectron microscopy map of Fab fragments of HM14c10 in a complex with DENV1 shows targeting of a discontinuous epitope that spans the adjacent surface of envelope protein dimers. As found previously, a human antibody specific for the related West Nile virus binds to a similar quaternary structure, suggesting that this could be an immunodominant epitope. These findings provide a structural and molecular context for durable, serotype-specific immunity to DENV infection.