scholarly journals Comparison of Immune Response To Human Rhinovirus C And Respiratory Syncytial Virus In Highly Differentiated Human Airway Epithelial Cells

2021 ◽  
Author(s):  
Xinhui Yuan ◽  
Li-li Pang ◽  
Jing Yang ◽  
Yu Jin
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Airway Epithelial Cells ◽  
Human Rhinovirus ◽  
Cytokine Secretion ◽  
Cdna Clones ◽  
Airway Epithelial ◽  
Syncytial Virus ◽  
Rhinovirus C ◽  
Air Liquid Interface

Abstract Background: Human rhinovirus C (HRV-C) accounts for a large proportion of HRV-related illnesses, but the immune response to HRV-C infection has not been elucidated. Our objective was to assess the effect of HRV-C on cytokine secretion in human bronchial epithelial (HBE) cells grown at air–liquid interface (ALI) and compare it with that of respiratory syncytial virus (RSV). Methods: HBE cells were differentiated at ALI culture and the full-length cDNA clones of HRV-C651 and HRV-C15, clinical isolates of HRV-C79 and HRV-C101, and two RSV isolates were inoculated in the HBE cells. The effect of HRV-C on cytokine secretion were assessed and compared with that of RSV.Results: HRV-Cs infects and propagates in fully differentiated HBE cells and significantly increased the secretion of IFN-λ1, CCL5, IP10, IL-6, IL-8, and MCP-1. The virus load positively correlated with the levels of the cytokines. HRV-C induced lower secretion of CCL5 (P=0.048), IL-6 (P=0.016), MCP-1 (P=0.008), and IL-8 (P=0.032), and similar secretion of IP10 (P=0.214) and IFN-λ1 (P=0.214) when compared with RSV. Conclusion: HBE ALI culture system supported HRV-C infection and propagation and HRV-C induced relatively weaker cytokine expression than RSV.

scholarly journals Protective role of Indoleamine 2,3 dioxygenase in Respiratory Syncytial Virus associated immune response in airway epithelial cells

Virology ◽  
2017 ◽  
Vol 512 ◽  
pp. 144-150 ◽  
Author(s):  
Devi Rajan ◽  
Raghavan Chinnadurai ◽  
Evan L. O'Keefe ◽  
Seyhan Boyoglu-Barnum ◽  
Sean O. Todd ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Epithelial Cells ◽  
Protective Role ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Indoleamine 2,3 Dioxygenase ◽  
Syncytial Virus

scholarly journals Bromodomain Containing Protein 4 (BRD4) Regulates Expression of its Interacting Coactivators in the Innate Response to Respiratory Syncytial Virus

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiaofang Xu ◽  
Morgan Mann ◽  
Dianhua Qiao ◽  
Yi Li ◽  
Jia Zhou ◽  
...  
Keyword(s):  
Immune Response ◽  
Extracellular Matrix ◽  
Transcription Factors ◽  
Respiratory Syncytial Virus ◽  
Innate Immune Response ◽  
Airway Epithelial Cells ◽  
Innate Immune ◽  
Airway Epithelial ◽  
Gene Regulatory ◽  
Syncytial Virus

Bromodomain-containing protein 4 plays a central role in coordinating the complex epigenetic component of the innate immune response. Previous studies implicated BRD4 as a component of a chromatin-modifying complex that is dynamically recruited to a network of protective cytokines by binding activated transcription factors, polymerases, and histones to trigger their rapid expression via transcriptional elongation. Our previous study extended our understanding of the airway epithelial BRD4 interactome by identifying over 100 functionally important coactivators and transcription factors, whose association is induced by respiratory syncytial virus (RSV) infection. RSV is an etiological agent of recurrent respiratory tract infections associated with exacerbations of chronic obstructive pulmonary disease. Using a highly selective small-molecule BRD4 inhibitor (ZL0454) developed by us, we extend these findings to identify the gene regulatory network dependent on BRD4 bromodomain (BD) interactions. Human small airway epithelial cells were infected in the absence or presence of ZL0454, and gene expression profiling was performed. A highly reproducible dataset was obtained which indicated that BRD4 mediates both activation and repression of RSV-inducible gene regulatory networks controlling cytokine expression, interferon (IFN) production, and extracellular matrix remodeling. Index genes of functionally significant clusters were validated independently. We discover that BRD4 regulates the expression of its own gene during the innate immune response. Interestingly, BRD4 activates the expression of NFκB/RelA, a coactivator that binds to BRD4 in a BD-dependent manner. We extend this finding to show that BRD4 also regulates other components of its functional interactome, including the Mediator (Med) coactivator complex and the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin (SMARC) subunits. To provide further insight into mechanisms for BRD4 in RSV expression, we mapped 7,845 RSV-inducible Tn5 transposase peaks onto the BRD4-dependent gene bodies. These were located in promoters and introns of cytostructural and extracellular matrix (ECM) formation genes. These data indicate that BRD4 mediates the dynamic response of airway epithelial cells to RNA infection by modulating the expression of its coactivators, controlling the expression of host defense mechanisms and remodeling genes through changes in promoter accessibility.

scholarly journals Metabolic Reprogramming of Nasal Airway Epithelial Cells Following Infant Respiratory Syncytial Virus Infection

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2055
Author(s):  
Andrew R. Connelly ◽  
Brian M. Jeong ◽  
Mackenzie E. Coden ◽  
Jacob Y. Cao ◽  
Tatiana Chirkova ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Epithelial Cells ◽  
Early Life ◽  
Airway Epithelial Cells ◽  
Metabolic Reprogramming ◽  
Flux Analysis ◽  
Nasal Airway ◽  
Airway Epithelial ◽  
Rsv Infection ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) is a seasonal mucosal pathogen that infects the ciliated respiratory epithelium and results in the most severe morbidity in the first six months of life. RSV is a common cause of acute respiratory infection during infancy and is an important early-life risk factor strongly associated with asthma development. While this association has been repeatedly demonstrated, limited progress has been made on the mechanistic understanding in humans of the contribution of infant RSV infection to airway epithelial dysfunction. An active infection of epithelial cells with RSV in vitro results in heightened central metabolism and overall hypermetabolic state; however, little is known about whether natural infection with RSV in vivo results in lasting metabolic reprogramming of the airway epithelium in infancy. To address this gap, we performed functional metabolomics, 13C glucose metabolic flux analysis, and RNA-seq gene expression analysis of nasal airway epithelial cells (NAECs) sampled from infants between 2–3 years of age, with RSV infection or not during the first year of life. We found that RSV infection in infancy was associated with lasting epithelial metabolic reprogramming, which was characterized by (1) significant increase in glucose uptake and differential utilization of glucose by epithelium; (2) altered preferences for metabolism of several carbon and energy sources; and (3) significant sexual dimorphism in metabolic parameters, with RSV-induced metabolic changes most pronounced in male epithelium. In summary, our study supports the proposed phenomenon of metabolic reprogramming of epithelial cells associated with RSV infection in infancy and opens exciting new venues for pursuing mechanisms of RSV-induced epithelial barrier dysfunction in early life.

scholarly journals Respiratory Syncytial Virus Up-regulates TLR4 and Sensitizes Airway Epithelial Cells to Endotoxin

2003 ◽  
Vol 278 (52) ◽  
pp. 53035-53044 ◽  
Author(s):  
Martha M. Monick ◽  
Timur O. Yarovinsky ◽  
Linda S. Powers ◽  
Noah S. Butler ◽  
A. Brent Carter ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Epithelial Cells ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Syncytial Virus
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