The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine (IMRIC), The Hebrew University Hadassah Medical School, Jerusalem 91120, Israel.
German Cancer Research Center, DKFZ, 69120 Heidelberg, Germany.
Cell Rep. 2016 May 17;15(7):1542-1553. doi: 10.1016/j.celrep.2016.04.042. Epub 2016 May 5.
HCMV is a highly sophisticated virus that has developed various mechanisms for immune evasion and viral dissemination throughout the body (partially mediated by neutrophils). NK cells play an important role in elimination of HCMV-infected cells. Both neutrophils and NK cells utilize similar sets of chemokine receptors to traffic, to and from, various organs. However, the mechanisms by which HCMV attracts neutrophils and not NK cells are largely unknown. Here, we show a unique viral protein, vCXCL1, which targets three chemokine receptors: CXCR1 and CXCR2 expressed on neutrophils and CXCR1 and CX3CR1 expressed on NK cells. Although vCXCL1 attracted both cell types, neutrophils migrated faster and more efficiently than NK cells through the binding of CXCR2. Therefore, we propose that HCMV has developed vCXCL1 to orchestrate its rapid systemic dissemination through preferential attraction of neutrophils and uses alternative mechanisms to counteract the later attraction of NK cells.
HCMV 是一种高度复杂的病毒，它已经开发出各种免疫逃避和病毒全身传播的机制（部分由中性粒细胞介导）。NK 细胞在清除 HCMV 感染细胞方面发挥着重要作用。中性粒细胞和 NK 细胞利用相似的趋化因子受体集在不同的器官之间迁移。然而，HCMV 吸引中性粒细胞而不是 NK 细胞的机制在很大程度上尚不清楚。在这里，我们展示了一种独特的病毒蛋白 vCXCL1，它靶向三种趋化因子受体：中性粒细胞上表达的 CXCR1 和 CXCR2 以及 NK 细胞上表达的 CXCR1 和 CX3CR1。尽管 vCXCL1 吸引了这两种细胞类型，但中性粒细胞通过与 CXCR2 的结合迁移得更快、更有效。因此，我们提出 HCMV 已经开发出 vCXCL1 通过优先吸引中性粒细胞来协调其快速的全身传播，并利用替代机制来对抗 NK 细胞的后续吸引。
