Respiratory syncytial virus and influenza virus regulate the host cell CCR1-HSP90 axis to facilitate their intracellular proliferation
10.3760/cma.j.cn112309-20240321-00104
- VernacularTitle:呼吸道合胞病毒和流感病毒通过调节宿主细胞CCR1-HSP90轴促进其胞内增殖
- Author:
Jiao LI
1
;
Ling XUE
;
Jiajun QIAO
;
Yijia CHEN
;
Haixia ZHANG
;
Yushan LIN
;
Xue GAO
;
Miao LI
;
Cuiqing MA
Author Information
1. 河北医科大学免疫教研室，河北省重大疾病免疫机制及干预重点实验室，石家庄 050017
- Publication Type:Journal Article
- Keywords:
RNA virus;
CCR1;
CCL5;
HSP90;
CDK1
- From:
Chinese Journal of Microbiology and Immunology
2025;45(1):17-25
- CountryChina
- Language:Chinese
-
Abstract:
Objective: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.
