scholarly journals Gene Expression Differences in Lungs of Mice during Secondary Immune Responses to Respiratory Syncytial Virus Infection

2010 ◽  
Vol 84 (18) ◽  
pp. 9584-9594 ◽  
Author(s):  
Annemieke Schuurhof ◽  
Louis Bont ◽  
Jeroen L. A. Pennings ◽  
Hennie M. Hodemaekers ◽  
Piet W. Wester ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Immune Responses ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Transcription Profiles ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Induced Immunity

ABSTRACT Vaccine-induced immunity has been shown to alter the course of a respiratory syncytial virus (RSV) infection both in murine models and in humans. To elucidate which mechanisms underlie the effect of vaccine-induced immunity on the course of RSV infection, transcription profiles in the lungs of RSV-infected mice were examined by microarray analysis. Three models were used: RSV reinfection as a model for natural immunity, RSV challenge after formalin-inactivated RSV vaccination as a model for vaccine-enhanced disease, and RSV challenge following vaccination with recombinant RSV virus lacking the G gene (ΔG-RSV) as a model for vaccine-induced immunity. Gene transcription profiles, histopathology, and viral loads were analyzed at 1, 2, and 5 days after RSV challenge. On the first 2 days after challenge, all mice displayed an expression pattern in the lung similar of that found in primary infection, showing a strong innate immune response. On day 5 after RSV reinfection or after challenge following ΔG-RSV vaccination, the innate immune response was waning. In contrast, in mice with vaccine-enhanced disease, the innate immune response 5 days after RSV challenge was still present even though viral replication was diminished. In addition, only in this group was Th2 gene expression induced. These findings support a hypothesis that vaccine-enhanced disease is mediated by prolonged innate immune responses and Th2 polarization in the absence of viral replication.

scholarly journals The Role of Alveolar Macrophages in the Improved Protection against Respiratory Syncytial Virus and Pneumococcal Superinfection Induced by the Peptidoglycan of Lactobacillus rhamnosus CRL1505

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1653 ◽  
Author(s):  
Patricia Clua ◽  
Mikado Tomokiyo ◽  
Fernanda Raya Tonetti ◽  
Md. Aminul Islam ◽  
Valeria García Castillo ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Innate Immune Response ◽  
Pneumococcal Pneumonia ◽  
Lactobacillus Rhamnosus ◽  
Innate Immune ◽  
Rsv Infection ◽  
Immunomodulatory Properties ◽  
Syncytial Virus

The nasal priming with nonviable Lactobacillus rhamnosus CRL1505 (NV1505) or its purified peptidoglycan (PG1505) differentially modulates the respiratory innate immune response in infant mice, improving their resistance to primary respiratory syncytial virus (RSV) infection and secondary pneumococcal pneumonia. In association with the protection against RSV-pneumococcal superinfection, it was found that NV1505 or PG1505 significantly enhance the numbers of CD11c+SiglecF+ alveolar macrophages (AMs) producing interferon (IFN)-β. In this work, we aimed to further advance in the characterization of the beneficial effects of NV1505 and PG1505 in the context of a respiratory superinfection by evaluating whether their immunomodulatory properties are dependent on AM functions. Macrophage depletion experiments and a detailed study of their production of cytokines and antiviral factors clearly demonstrated the key role of this immune cell population in the improvement of both the reduction of pathogens loads and the protection against lung tissue damage induced by the immunobiotic CRL1505 strain. Studies at basal conditions during primary RSV or S. pneumoniae infections, as well as during secondary pneumococcal pneumonia, brought the following five notable findings regarding the immunomodulatory effects of NV1505 and PG1505: (a) AMs play a key role in the beneficial modulation of the respiratory innate immune response and protection against RSV infection, (b) AMs are necessary for improved protection against primary and secondary pneumococcal pneumonia, (c) the generation of activated/trained AMs would be essential for the enhanced protection against respiratory pathogens, (d) other immune and nonimmune cell populations in the respiratory tract may contribute to the protection against bacterial and viral infections, and (e) the immunomodulatory properties of NV1505 and PG1505 are strain-specific. These findings significantly improve our knowledge about the immunological mechanisms involved in the modulation of respiratory immunity induced by beneficial microbes.

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 Host Transcription Profiles upon Primary Respiratory Syncytial Virus Infection

2007 ◽  
Vol 81 (11) ◽  
pp. 5958-5967 ◽  
Author(s):  
Riny Janssen ◽  
Jeroen Pennings ◽  
Hennie Hodemaekers ◽  
Annemarie Buisman ◽  
Marijke van Oosten ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Lymph Nodes ◽  
Viral Replication ◽  
Transcriptional Level ◽  
Type I ◽  
Lung Pathology ◽  
Transcription Profiles ◽  
Rsv Infection ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) is a common cause of severe lower respiratory tract infection in children. Severe RSV disease is related to an inappropriate immune response to RSV resulting in enhanced lung pathology which is influenced by host genetic factors. To gain insight into the early pathways of the pathogenesis of and immune response to RSV infection, we determined the transcription profiles of lungs and lymph nodes on days 1 and 3 after infection of mice. Primary RSV infection resulted in a rapid but transient innate, proinflammatory response, as exemplified by the induction of a large number of type I interferon-regulated genes and chemokine genes, genes involved in inflammation, and genes involved in antigen processing. Interestingly, this response is much stronger on day 1 than on day 3 after infection, indicating that the strong transcriptional response in the lung precedes the peak of viral replication. Surprisingly, the set of down-regulated genes was small and none of these genes displayed strong down-regulation. Responses in the lung-draining lymph nodes were much less prominent than lung responses and are suggestive of NK cell activation. Our data indicate that at time points prior to the peak of viral replication and influx of inflammatory cells, the local lung response, measured at the transcriptional level, has already dampened down. The processes and pathways induced shortly after RSV infection can now be used for the selection of candidate genes for human genetic studies of children with severe RSV infection.

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 Depletion of TAX1BP1 amplifies innate immune responses during respiratory syncytial virus infection

2021 ◽  
Author(s):  
Delphyne Descamps ◽  
Andressa Peres de Oliveira ◽  
Lorène Gonnin ◽  
Sarah Madrières ◽  
Jenna Fix ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Antiviral Response ◽  
Innate Immune ◽  
Cellular Proteins ◽  
Separation Mechanism ◽  
Efficient Treatment ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Host Antiviral Response

Respiratory syncytial virus (RSV) is the main cause of acute respiratory infections in young children, and also has a major impact in the elderly and immunocompromised people. In the absence of vaccine or efficient treatment, a better understanding of RSV interactions with the host antiviral response during infection is needed. Previous studies revealed that cytoplasmic inclusion bodies (IBs) where viral replication and transcription occur could play a major role in the control of innate immunity during infection by recruiting cellular proteins involved in the host antiviral response. We recently showed that the morphogenesis of IBs relies on a liquid-liquid phase separation mechanism depending on the interaction between viral nucleoprotein (N) and phosphoprotein (P). These scaffold proteins are expected to play a central role in the recruitment of cellular proteins to IBs. Here, we performed a yeast two-hybrid screen using RSV N protein as a bait, and identified the cellular protein TAX1BP1 as a potential partner of N. This interaction was validated by pulldown and immunoprecipitation assays. We showed that TAX1BP1 suppression has only a limited impact on RSV infection in cell cultures. On the contrary, in vivo experiments showed that RSV replication is decreased in TAX1BP1KO mice, whereas the production of inflammatory and antiviral cytokines is enhanced. In vitro infection of either wild-type or TAX1BP1KO alveolar macrophages confirmed that the innate immune response to RSV infection is enhanced in the absence of TAX1BP1. Altogether, our results suggest that RSV could hijack TAX1BP1 to restrain the host immune response during infection.

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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