Varicella zoster virus glycoprotein C increases chemokine-mediated leukocyte migration
Varicella zoster virus glycoprotein C increases chemokine-mediated leukocyte migration
复制标题
DOI：
10.1371/journal.ppat.1006346
复制
发表时间：
2017-05-01
期刊：
影响因子：
6.7
通讯作者：
Viejo-Borbolla, Abel
中科院分区：
文献类型：
--
作者：
Gonzalez-Motos, Victor;Juergens, Carina;Viejo-Borbolla, Abel
水痘带状疱疹病毒（VZV）是一种高度流行的人类病原体，它在周围神经系统的神经元中产生潜伏期。原发性感染引起水痘，而再激活导致带状疱疹，这通常是成年人的慢性疼痛。在呼吸道上皮细胞感染后，VZV通过劫持扁桃体和其他区域淋巴结中的白细胞（包括T细胞）并改变其活性而在宿主内传播。尽管其在发病机制中的重要性，传播的机制仍然知之甚少。在这里，我们解决了VZV对白细胞迁移的影响，并发现纯化的重组可溶性胞外域VZV糖蛋白C（rSgC）结合趋化因子具有高亲和力。功能实验表明，VZV rSgC增强趋化因子活性，增强单核细胞和T细胞系的迁移，最重要的是，在低趋化因子浓度下，人扁桃体白细胞。趋化因子活性的结合和增强通过含有预测的免疫球蛋白样结构域的gC胞外域的C末端部分发生。VZV rSgC的作用机制需要与趋化因子相互作用并通过趋化因子受体进行信号传导。最后，我们表明，VZV病毒颗粒增强趋化因子依赖性T细胞迁移和gC是部分需要这种活动。我们认为VZV gC活性促进了白细胞的募集和随后的感染，从而增强了VZV在人体内的全身传播。
Varicella zoster virus (VZV) is a highly prevalent human pathogen that establishes latency in neurons of the peripheral nervous system. Primary infection causes varicella whereas reactivation results in zoster, which is often followed by chronic pain in adults. Following infection of epithelial cells in the respiratory tract, VZV spreads within the host by hijacking leukocytes, including T cells, in the tonsils and other regional lymph nodes, and modifying their activity. In spite of its importance in pathogenesis, the mechanism of dissemination remains poorly understood. Here we addressed the influence of VZV on leukocyte migration and found that the purified recombinant soluble ectodomain of VZV glycoprotein C (rSgC) binds chemokines with high affinity. Functional experiments show that VZV rSgC potentiates chemokine activity, enhancing the migration of monocyte and T cell lines and, most importantly, human tonsillar leukocytes at low chemokine concentrations. Binding and potentiation of chemokine activity occurs through the C-terminal part of gC ectodomain, containing predicted immunoglobulin-like domains. The mechanism of action of VZV rSgC requires interaction with the chemokine and signalling through the chemokine receptor. Finally, we show that VZV viral particles enhance chemokine-dependent T cell migration and that gC is partially required for this activity. We propose that VZV gC activity facilitates the recruitment and subsequent infection of leukocytes and thereby enhances VZV systemic dissemination in humans.