scholarly journals TLR-4 andCD14 Polymorphisms in Respiratory Syncytial Virus Associated Disease

2006 ◽  
Vol 22 (5-6) ◽  
pp. 303-308 ◽  
Author(s):  
Beena Puthothu ◽  
Johannes Forster ◽  
Andrea Heinzmann ◽  
Marcus Krueger
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Amino Acid ◽  
Adaptive Immune Response ◽  
Host Cells ◽  
Respiratory Pathogen ◽  
Trend Test ◽  
Associated Diseases ◽  
Rsv Infection ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) is the most common viral respiratory pathogen during infancy world wide. It induces innate and adaptive immune response in host cells. The toll like receptor 4 (TLR4)/CD14 complex is particularly important for the initiation of an innate immune response to RSV. Thus we were interested whether an association exists between severe RSV associated diseases and polymorphisms within TLR4 and CD14.We genotyped the CD14 promotor polymorphism -C159T and the two common TLR4 amino acid variants (D259G, and T359I) in 131 infants with severe RSV associated diseases and 270 controls. Statistical analyses of single polymorphisms made use of the Armitage’s trend test, haplotypes were calculated by FAMHAP, FASTEHPLUS and Arlequin.All polymorphisms were in Hardy Weinberg Equilibrium. We found marginal association between amino acid exchange D259G in TLR4 with RSV infectionp= 0.0545). Furthermore, haplotypes analysis of the two TLR4 polymorphisms by three independent programs revealed association of haplotypes with severe RSV infection (p≤ 0.0010). In contrast, the promotor polymorphism within CD14 was not associated with susceptibility to RSV disease. We conclude from our study, that TLR4 polymorphisms, and particularly the haplotypes, may influence the genetic predisposition to severe RSV infection.

scholarly journals Polymorphisms of Toll Like Receptors in the Genetics of Severe RSV Associated Diseases

2008 ◽  
Vol 25 (1) ◽  
pp. 59-65 ◽  
Author(s):  
Beena Mailaparambil ◽  
Marcus Krueger ◽  
Jessica Heinze ◽  
Johannes Forster ◽  
Andrea Heinzmann
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Trend Test ◽  
Toll Like Receptors ◽  
Major Health Problem ◽  
Associated Diseases ◽  
Wide Range ◽  
Rsv Infection ◽  
Syncytial Virus

Toll like receptors (TLRs) are an essential part of the innate immune response. So far, ten different TLRs were identified in humans. They recognize a wide range of microbial and viral pathogens. Infection by respiratory syncytial virus (RSV) is still a major health problem, about 2% of all children are hospitalised due to RSV bronchiolitis during their first 2 years of live. TLR4 has already been described in association with RSV associated diseases by us and others.Thus we were interested whether other TLRs are also involved in the genetics of severe RSV infection. We genotyped 19 polymorphisms in the autosomal TLRs, these are TLR1, 2, 3, 5, 6, 9 and 10. Association analyses by the Armitage's Trend test revealed weak association of one TLR9 promoter polymorphism with RSV infection (p= 0.013). In addition, association was found with TLR10 haplotypes (p= 0.024).We conclude from our data – that – although we can not rule out a minor involvement ofTLR9polymorphism andTLR10haplotypes – TLRs other than TLR4 do not play a major role in the genetics of severe RSV associated diseases. Future studies should focus on additional genes of the innate immune response.

scholarly journals Mathematical modelling identifies the role of adaptive immunity as a key controller of respiratory syncytial virus in cotton rats

2019 ◽  
Vol 16 (160) ◽  
pp. 20190389 ◽  
Author(s):  
Darren Wethington ◽  
Olivia Harder ◽  
Karthik Uppulury ◽  
William C. L. Stewart ◽  
Phylip Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Mathematical Modelling ◽  
Adaptive Immune Response ◽  
Viral Titre ◽  
Adaptive Immune ◽  
Rsv Infection ◽  
Cotton Rats ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) is a common virus that can have varying effects ranging from mild cold-like symptoms to mortality depending on the age and immune status of the individual. We combined mathematical modelling using ordinary differential equations (ODEs) with measurement of RSV infection kinetics in primary well-differentiated human bronchial epithelial cultures in vitro and in immunocompetent and immunosuppressed cotton rats to glean mechanistic details that underlie RSV infection kinetics in the lung. Quantitative analysis of viral titre kinetics in our mathematical model showed that the elimination of infected cells by the adaptive immune response generates unique RSV titre kinetic features including a faster timescale of viral titre clearance than viral production, and a monotonic decrease in the peak RSV titre with decreasing inoculum dose. Parameter estimation in the ODE model using a nonlinear mixed effects approach revealed a very low rate (average single-cell lifetime > 10 days) of cell lysis by RSV before the adaptive immune response is initiated. Our model predicted negligible changes in the RSV titre kinetics at early times post-infection (less than 5 dpi) but a slower decay in RSV titre in immunosuppressed cotton rats compared to that in non-suppressed cotton rats at later times (greater than 5 dpi) in silico. These predictions were in excellent agreement with the experimental results. Our combined approach quantified the importance of the adaptive immune response in suppressing RSV infection in cotton rats, which could be useful in testing RSV vaccine candidates.

scholarly journals Differential Mucin Expression by Respiratory Syncytial Virus and Human Metapneumovirus Infection in Human Epithelial Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Ma. Del Rocío Baños-Lara ◽  
Boyang Piao ◽  
Antonieta Guerrero-Plata
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Epithelial Cells ◽  
Viral Infections ◽  
Human Metapneumovirus ◽  
Human Epithelial Cells ◽  
Mucin Expression ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Disease

Mucins (MUC) constitute an important component of the inflammatory and innate immune response. However, the expression of these molecules by respiratory viral infections is still largely unknown. Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two close-related paramyxoviruses that can cause severe low respiratory tract disease in infants and young children worldwide. Currently, there is not vaccine available for neither virus. In this work, we explored the differential expression of MUC by RSV and hMPV in human epithelial cells. Our data indicate that the MUC expression by RSV and hMPV differs significantly, as we observed a stronger induction of MUC8, MUC15, MUC20, MUC21, and MUC22 by RSV infection while the expression of MUC1, MUC2, and MUC5B was dominated by the infection with hMPV. These results may contribute to the different immune response induced by these two respiratory viruses.

scholarly journals Crawling with Virus: Translational Insights from a Neonatal Mouse Model on the Pathogenesis of Respiratory Syncytial Virus in Infants

2015 ◽  
Vol 90 (1) ◽  
pp. 2-4 ◽  
Author(s):  
Dahui You ◽  
Jordy Saravia ◽  
David Siefker ◽  
Bishwas Shrestha ◽  
Stephania A. Cormier
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Mouse Model ◽  
Severe Infection ◽  
Neonatal Mouse ◽  
Cell Type ◽  
Human Infants ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Infant Immune Response

The infant immune response to respiratory syncytial virus (RSV) remains incompletely understood. Here we review the use of a neonatal mouse model of RSV infection to mimic severe infection in human infants. We describe numerous age-specific responses, organized by cell type, observed in RSV-infected neonatal mice and draw comparisons (when possible) to human infants.

RESPIRATORY SYNCYTIAL VIRUS LUNG INFECTION IN INFANTS: IMMUNOREGULATORY ROLE OF INFECTED ALVEOLAR MACROPHAGES

PEDIATRICS ◽  
1995 ◽  
Vol 96 (2) ◽  
pp. 391-391
Author(s):  
Leon S. Greos
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Lung Injury ◽  
Alveolar Macrophages ◽  
Lung Infection ◽  
Local Immune Response ◽  
Rsv Infection ◽  
Syncytial Virus

Alveolar macrophages are infected by RSV in vivo and coexpress potent immunomodulatory molecules that potentially regulate local immune response or lung injury caused by RSV infection.

scholarly journals The Human Immune Response to Respiratory Syncytial Virus Infection

2017 ◽  
Vol 30 (2) ◽  
pp. 481-502 ◽  
Author(s):  
Clark D. Russell ◽  
Stefan A. Unger ◽  
Marc Walton ◽  
Jürgen Schwarze
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
T Cell ◽  
T Cell Response ◽  
Rsv Infection ◽  
Human Immune Response ◽  
Ifn Γ ◽  
Human Immune ◽  
Syncytial Virus

SUMMARY Respiratory syncytial virus (RSV) is an important etiological agent of respiratory infections, particularly in children. Much information regarding the immune response to RSV comes from animal models and in vitro studies. Here, we provide a comprehensive description of the human immune response to RSV infection, based on a systematic literature review of research on infected humans. There is an initial strong neutrophil response to RSV infection in humans, which is positively correlated with disease severity and mediated by interleukin-8 (IL-8). Dendritic cells migrate to the lungs as the primary antigen-presenting cell. An initial systemic T-cell lymphopenia is followed by a pulmonary CD8+ T-cell response, mediating viral clearance. Humoral immunity to reinfection is incomplete, but RSV IgG and IgA are protective. B-cell-stimulating factors derived from airway epithelium play a major role in protective antibody generation. Gamma interferon (IFN-γ) has a strongly protective role, and a Th2-biased response may be deleterious. Other cytokines (particularly IL-17A), chemokines (particularly CCL-5 and CCL-3), and local innate immune factors (including cathelicidins and IFN-λ) contribute to pathogenesis. In summary, neutrophilic inflammation is incriminated as a harmful response, whereas CD8+ T cells and IFN-γ have protective roles. These may represent important therapeutic targets to modulate the immunopathogenesis of RSV infection.

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 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 Role of G2-S16 Polyanionic Carbosilane Dendrimer in the Prevention of Respiratory Syncytial Virus Infection In Vitro and In Vivo in Mice

Polymers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 2141
Author(s):  
Ignacio Rodriguez-Izquierdo ◽  
Rafael Ceña-Diez ◽  
Maria Jesús Serramia ◽  
Rosa Rodriguez-Fernández ◽  
Isidoro Martínez ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Cell Surface ◽  
Host Cells ◽  
Carbosilane Dendrimer ◽  
Rsv Infection ◽  
Host Cell Surface ◽  
Syncytial Virus

The respiratory syncytial virus (RSV) causes respiratory infection and bronchiolitis, requiring hospitalization mainly in infants. The interaction between RSV, envelope glycoproteins G and F, and cell surface heparan sulfate proteoglycans (HSPG) is required for binding and entry into the host cells. A G2-S16 polyanionic carbosilane dendrimer was identified as a possible RSV inhibitor. We speculated that the G2-S16 dendrimer adheres to the host cell-surface HSPG, acts through binding to HS receptors, and prevents further RSV infection. The G2-S16 dendrimer was non-toxic when applied intranasally to Balb/c mice, and interestingly enough, this G2-S16 dendrimer inhibits 85% RSV. Therefore, our G2-S16 dendrimer could be a candidate for developing a new possible therapy against RSV infection.

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