Meineke Robert, Agac Ayse, Knittler Marie-Christin, Ludlow Martin, Osterhaus Albert D M E, Rimmelzwaan Guus F
Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, Hannover, Germany.
Npj Viruses. 2024 Dec 5;2(1):63. doi: 10.1038/s44298-024-00075-9.
The soluble form of the Respiratory Syncytial Virus (RSV) G protein (sG) bears resemblance to the chemokine fractalkine (CX₃CL1). Both RSV sG and CXCL1 possess a mucin-like domain and a CXC motif, exist in membrane-associated and soluble forms, and bind to the CX₃CR1 receptor expressed on immune and epithelial cells. To explore the biological significance of RSV sG and CX₃CR1 interaction, we produced wild type (WT) and CX₃C motif-deficient (CXC) RSV sG proteins and determined their effects on CX₃CR1 signaling in monocytic cells. Both CXC- and WT RSV sG failed to activate CX₃CR1 signaling directly. However, WT sG competed with CX₃CL1 for CX₃CR1 binding and reduced CXCL1-induced CX₃CR1-activation, monocyte migration, and adhesion. The CX₃C motif of sG was crucial for competitive blocking of CXCL1-mediated activation, as CX₃C sG did not affect these CX₃CR1 functions significantly. Thus, blockade of CX₃CR1 signaling by sG may allow RSV to dampen host immune responses.
呼吸道合胞病毒（RSV）G蛋白的可溶性形式（sG）与趋化因子fractalkine（CX₃CL1）相似。RSV sG和CXCL1都具有粘蛋白样结构域和CXC基序，以膜相关形式和可溶性形式存在，并与免疫细胞和上皮细胞上表达的CX₃CR1受体结合。为了探究RSV sG与CX₃CR1相互作用的生物学意义，我们制备了野生型（WT）和CXC基序缺陷型（CXC）的RSV sG蛋白，并确定了它们对单核细胞中CX₃CR1信号传导的影响。CXC型和WT型RSV sG均未能直接激活CX₃CR1信号传导。然而，WT sG与CX₃CL1竞争CX₃CR1结合，并降低CXCL1诱导的CX₃CR1激活、单核细胞迁移和黏附。sG的CXC基序对于竞争性阻断CXCL1介导的激活至关重要，因为CXC sG对这些CX₃CR1功能没有显著影响。因此，sG对CX₃CR1信号传导的阻断可能使RSV减弱宿主免疫反应。
