scholarly journals Respiratory syncytial virus infection of newborn CX3CR1-deficent mice induces a pathogenic pulmonary innate immune response

JCI Insight ◽  
2017 ◽  
Vol 2 (17) ◽  
Author(s):  
Sudipta Das ◽  
Mahesh Raundhal ◽  
Jie Chen ◽  
Timothy B. Oriss ◽  
Rachael Huff ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Virus Infection ◽  
Innate Immune Response ◽  
Respiratory Syncytial Virus Infection ◽  
Innate Immune ◽  
Syncytial Virus

scholarly journals Human metapneumovirus induces more severe disease and stronger innate immune response in BALB/c mice as compared with respiratory syncytial virus

2007 ◽  
Vol 8 (1) ◽  
Author(s):  
Barbara Huck ◽  
Dieter Neumann-Haefelin ◽  
Annette Schmitt-Graeff ◽  
Markus Weckmann ◽  
Jörg Mattes ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Innate Immune Response ◽  
Severe Disease ◽  
Human Metapneumovirus ◽  
Innate Immune ◽  
Syncytial Virus

scholarly journals siRNA-Mediated Simultaneous Regulation of the Cellular Innate Immune Response and Human Respiratory Syncytial Virus Replication

Biomolecules ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. 165 ◽  
Author(s):  
María Martín-Vicente ◽  
Salvador Resino ◽  
Isidoro Martínez
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Virus Replication ◽  
Innate Immune Response ◽  
Human Respiratory Syncytial Virus ◽  
Innate Immune ◽  
Viral Fusion ◽  
Small Interfering Rnas ◽  
Syncytial Virus ◽  
Nucleoprotein N

Human respiratory syncytial virus (HRSV) infection is a common cause of severe lower respiratory tract diseases such as bronchiolitis and pneumonia. Both virus replication and the associated inflammatory immune response are believed to be behind these pathologies. So far, no vaccine or effective treatment is available for this viral infection. With the aim of finding new strategies to counteract HRSV replication and modulate the immune response, specific small interfering RNAs (siRNAs) were generated targeting the mRNA coding for the viral fusion (F) protein or nucleoprotein (N), or for two proteins involved in intracellular immune signaling, which are named tripartite motif-containing protein 25 (TRIM25) and retinoic acid-inducible gene-I (RIG-I). Furthermore, two additional bispecific siRNAs were designed that silenced F and TRIM25 (TRIM25/HRSV-F) or N and RIG-I (RIG-I/HRSV-N) simultaneously. All siRNAs targeting N or F, but not those silencing TRIM25 or RIG-I alone, significantly reduced viral titers. However, while siRNAs targeting F inhibited only the expression of the F mRNA and protein, the siRNAs targeting N led to a general inhibition of viral mRNA and protein expression. The N-targeting siRNAs also induced a drastic decrease in the expression of genes of the innate immune response. These results show that both virus replication and the early innate immune response can be regulated by targeting distinct viral products with siRNAs, which may be related to the different role of each protein in the life cycle of the virus.

Platelets Modulate Innate Immune Response Against Human Respiratory Syncytial Virus In Vitro

2017 ◽  
Vol 30 (8) ◽  
pp. 576-581 ◽  
Author(s):  
Vesla I. Kullaya ◽  
Quirijn de Mast ◽  
Andre van der Ven ◽  
Hicham elMoussaoui ◽  
Gibson Kibiki ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Innate Immune Response ◽  
Human Respiratory Syncytial Virus ◽  
Innate Immune ◽  
Syncytial Virus

scholarly journals Double-Stranded RNA-Activated Protein Kinase Regulates Early Innate Immune Responses During Respiratory Syncytial Virus Infection

2010 ◽  
Vol 30 (4) ◽  
pp. 263-272 ◽  
Author(s):  
Radiah A. Corn Minor ◽  
Gino V. Limmon ◽  
Laura Miller-DeGraff ◽  
Darlene Dixon ◽  
Danica M.K. Andrews ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Protein Kinase ◽  
Virus Infection ◽  
Immune Responses ◽  
Respiratory Syncytial Virus Infection ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Double Stranded Rna ◽  
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 p53-responsive TLR8 SNP enhances human innate immune response to respiratory syncytial virus

2019 ◽  
Vol 129 (11) ◽  
pp. 4875-4884 ◽  
Author(s):  
Daniel Menendez ◽  
Joyce Snipe ◽  
Jacqui Marzec ◽  
Cynthia L. Innes ◽  
Fernando P. Polack ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Syncytial Virus

scholarly journals Respiratory Syncytial virus NS1 protein targets the transactivator binding domain of MED25

2021 ◽  
Author(s):  
Vincent Basse ◽  
Jiawei Dong ◽  
Andressa Peres de Oliveira ◽  
Pierre-Olivier Vidalain ◽  
Frédéric Tangy ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Rna Polymerase Ii ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Transactivation Domain ◽  
Ns1 Protein ◽  
Syncytial Virus ◽  
Acid Domain

Respiratory syncytial virus has evolved a unique strategy to evade host immune response by coding for two non-structural proteins NS1 and NS2. Recently it was shown that in infected cells, nuclear NS1 could be involved in transcription regulation of host genes linked to innate immune response, via an interaction with chromatin and the Mediator complex. Here we identified the MED25 Mediator subunit as an NS1 interactor in a yeast two-hybrid screen. We demonstrate that NS1 directly interacts with MED25 in vitro and in cellula, and that this interaction involves the C-terminal α3 helix of NS1 and the MED25 ACID domain. More specifically we showed by NMR that the NS1 α3 sequence primarily binds to the MED25 ACID H2 face, which is a transactivation domain (TAD) binding site for transcription regulators such as ATF6α, a master regulator of ER stress response activated upon viral infection. Moreover, we found out that the NS1 α3 helix could compete with ATF6α TAD binding to MED25. This finding points to a mechanism of NS1 interfering with innate immune response by impairing recruitment by cellular TADs of the Mediator via MED25 and hence transcription of specific genes by RNA polymerase II.

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