PLoS One：抗体促使登革热病毒感染机制

众所周知，不成熟的登革热病毒(DENV)是没有感染性的，但是最近荷兰格罗宁根大学的研究人员Jolanda M. Smit等人却发现：抗前体膜(prM)的抗体会导致这种不成熟病毒对有Fcγ受体表达的细胞具有传染性。在DENV抗体与病毒包膜以及前体膜(prM)蛋白相互作用后，会引起抗体依赖性病毒感染增强，结果导致更严重的疾病。相关论文发表在3月14日的美国科学公共图书馆—综合》（PLoS One）上。

由于病毒在成熟过程中低效率的加工，不成熟的DENV颗粒会极其丰富的存在于标准病毒的制剂中。可是结构分析显示包膜蛋白暴露于不成熟的病毒颗粒中。这提示了研究人员去调查是否是包膜蛋白的抗体促使了这些不成熟的病毒颗粒具有感染性。

基于明显的结构区域差异，研究人员分析了具有增强感染作用的27个抗包膜蛋白的抗体，结果发现，里面有23个不成熟颗粒，其中有15个增强了不成熟的DENV的感染活性。在发现这个结果的重要性后，他们在建立好的感染西尼罗河病毒(WNV)的老鼠模型身上做了活体的实验。结果显著表明，在抗包膜蛋白单克隆抗体或者是免疫血清的调理下，被不成熟的WNV感染后的老鼠，会产生了剂量依赖方式的致死感染。然而，没有抗体作用的不成熟的WNV不会引起发病或者死亡。

此外，对标准DENV制剂的感染增强实验研究表明，标准病毒制剂中出现的由前体膜包含的病毒颗粒，会促进抗体依赖性增强感染。总的来说，这些结果说明一个问题：抗结构蛋白prM以及包膜蛋白的抗体，通过增强前体膜包含不成熟的或者是部分成熟的病毒颗粒的感染，可以促进发病。（生物谷Bioon.com）

doi: 10.1371/journal.pone.0029957
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Antibodies against the Envelope Glycoprotein Promote Infectivity of Immature Dengue Virus Serotype 2

Júlia M. da Silva Voorham, Izabela A. Rodenhuis-Zybert, Nilda Vanesa Ayala Nu?ez, Tonya M. Colpitts, Heidi van der Ende-Metselaar, Erol Fikrig, Michael S. Diamond, Jan Wilschut1, Jolanda M. Smit.

Cross-reactive dengue virus (DENV) antibodies directed against the envelope (E) and precursor membrane (prM) proteins are believed to contribute to the development of severe dengue disease by facilitating antibody-dependent enhancement of infection.We and others recently demonstrated that anti-prM antibodies render essentially non-infectious immature DENV infectious in Fcγ-receptor-expressing cells. Immature DENV particles are abundantly present in standard (st) virus preparations due to inefficient processing of prM to M during virus maturation. Structural analysis has revealed that the E protein is exposed in immature particles and this prompted us to investigate whether antibodies to E render immature particles infectious. To this end, we analyzed the enhancing properties of 27 anti-E antibodies directed against distinct structural domains.Of these, 23 bound to immature particles, and 15 enhanced infectivity of immature DENV in a furin-dependent manner. The significance of these findings was subsequently tested in vivo using the well-established West Nile virus (WNV) mouse model. Remarkably, mice injected with immature WNV opsonized with anti-E mAbs or immune serum produced a lethal infection in a dose-dependent manner, whereas in the absence of antibody immature WNV virions caused no morbidity or mortality.Furthermore, enhancement infection studies with standard (st) DENV preparations opsonized with anti-E mAbs in the presence or absence of furin inhibitor revealed that prM-containing particles present within st virus preparations contribute to antibody-dependent enhancement of infection. Taken together, our results support the notion that antibodies against the structural proteins prM and E both can promote pathogenesis by enhancing infectivity of prM-containing immature and partially mature flavivirus particles.