摘要目的:探究呼吸道合胞病毒(respiratory syncytial virus，RSV)和流感病毒感染过表达趋化因子受体1[chemokine (C-C motif) receptor 1，CCR1]的呼吸道上皮细胞后，胞内病毒载量显著降低的潜在机制。方法:RSV、甲型流感病毒(H1N1、H3N2)、乙型流感病毒(influenza B virus，FluB)感染A549细胞后，qRT-PCR、ELISA、Western blot检测宿主细胞趋化因子配体5[chemokine (C-C motif) ligand 5，CCL5]及CCR1的表达情况。对A549细胞过表达或敲低CCR1后，qRT-PCR、Western blot检测RSV、H1N1、H3N2、FluB感染后CCR1、热休克蛋白90(heat shock protein 90, HSP90)、细胞周期蛋白依赖性激酶1(cyclin-dependent kinase 1，CDK1)及病毒蛋白质的表达情况。用CCL5蛋白刺激过表达CCR1的A549细胞，Western blot检测HSP90和CDK1的表达情况，免疫共沉淀检测HSP90与CCR1的相互作用。RSV、H1N1、H3N2感染CCR1 －/－小鼠后，Western blot检测HSP90、CDK1、病毒蛋白质的表达，HE染色观察肺部炎症情况。采用单因素方差分析和 t检验进行统计学分析。 结果:RSV、H1N1、H3N2、FluB感染A549细胞后诱导CCL5高表达( P<0.05)，而CCR1整体呈下调趋势。CCL5活化其受体CCR1后通过抑制HSP90的活性来抑制RSV和流感病毒的复制( P<0.05)。CCR1 －/－小鼠实验证实HSP90的活性增强促进了RSV和流感病毒的复制。 结论:RSV和流感病毒可能通过下调呼吸道上皮细胞的CCR1水平来减弱CCL5与CCR1的结合，从而减弱CCR1对HSP90活性的抑制作用，以逃避宿主细胞的免疫防御。

abstractsObjective:To investigate the underlying mechanism behind the significant reduction in intracellular virus loads after respiratory syncytial virus (RSV) and influenza viruses infect respiratory epithelial cells overexpressing the chemokine (C-C motif) receptor 1 (CCR1).Methods:A549 cells were infected with respiratory syncytial virus (RSV), influenza A viruses (H1N1, H3N2), or influenza B virus (FluB), and the expression of chemokine (C-C motif) ligand 5 (CCL5) and CCR1 were detected by qRT-PCR, ELISA, and Western blot. After overexpressing or knocking down CCR1 in A549 cells, these cells were infected with RSV, H1N1, H3N2, or FluB, and the expression of CCR1, heat shock protein 90 (HSP90), cyclin-dependent kinase 1 (CDK1), and viral proteins were detected by qRT-PCR and Western blot. After stimulating CCR1-overexpressed A549 cells with CCL5, Western blot was used to detect the expression of HSP90 and CDK1, and co-immunoprecipitation was used to detect the interaction between HSP90 and CCR1. CCR1 -/- mice were infected with RSV, H1N1, or H3N2 to observe the changes in the expression of HSP90, CDK1, and viral proteins with Western blot, and the inflammation in lung tissues with HE staining. One-way analysis of variance and t test were used for statistical analysis. Results:RSV, H1N1, H3N2, and FluB infections induced high expression of CCL5 in A549 cells ( P<0.05), but the expression of CCR1 showed an overall downward trend. After activating its receptor CCR1, CCL5 inhibited the replication of RSV and influenza viruses by suppressing the activity of HSP90 ( P<0.05). The experiments conducted on CCR1 -/- mice confirmed that the enhanced activity of HSP90 facilitated the replication of RSV and influenza viruses. Conclusion:RSV and influenza viruses may reduce the binding of CCL5 to CCR1 by downregulating the expression of CCR1 in respiratory epithelial cells, thereby weakening the inhibitory effect of CCR1 on HSP90 activity, which enables them to evade host immune defense.