scholarly journals A systems genomics approach uncovers molecular associates of RSV severity

2021 ◽  
Vol 17 (12) ◽  
pp. e1009617
Author(s):  
Matthew N. McCall ◽  
Chin-Yi Chu ◽  
Lu Wang ◽  
Lauren Benoodt ◽  
Juilee Thakar ◽  
...  
Keyword(s):  
Critical Role ◽  
Back Propagation ◽  
Principal Component ◽  
Penalized Regression ◽  
Cell Receptor ◽  
Feature Weight ◽  
Rsv Infection ◽  
B Cell Receptor Signaling ◽  
Syncytial Virus ◽  
Omic Data Integration

Respiratory syncytial virus (RSV) infection results in millions of hospitalizations and thousands of deaths each year. Variations in the adaptive and innate immune response appear to be associated with RSV severity. To investigate the host response to RSV infection in infants, we performed a systems-level study of RSV pathophysiology, incorporating high-throughput measurements of the peripheral innate and adaptive immune systems and the airway epithelium and microbiota. We implemented a novel multi-omic data integration method based on multilayered principal component analysis, penalized regression, and feature weight back-propagation, which enabled us to identify cellular pathways associated with RSV severity. In both airway and immune cells, we found an association between RSV severity and activation of pathways controlling Th17 and acute phase response signaling, as well as inhibition of B cell receptor signaling. Dysregulation of both the humoral and mucosal response to RSV may play a critical role in determining illness severity.

scholarly journals A systems genomics approach uncovers molecular associates of RSV severity

2020 ◽  
Author(s):  
Matthew N McCall ◽  
Chin-Yi Chu ◽  
Lu Wang ◽  
Lauren Benoodt ◽  
Juilee Thakar ◽  
...  
Keyword(s):  
Critical Role ◽  
Back Propagation ◽  
Principal Component ◽  
Penalized Regression ◽  
Cell Receptor ◽  
Novel Approach ◽  
Feature Weight ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Omic Data Integration

Globally, RSV infection results in millions of hospitalizations and thousands of deaths each year. Specific factors that contribute to disease severity, such as premature birth and certain comorbidities, are well established. Additionally, genetic variants resulting in alterations in the adaptive and innate immune response appear to be associated with RSV severity. While previous studies focused on a single aspect of the disease, we jointly modeled the association of disparate data modalities with RSV severity. To investigate the host response to respiratory syncytial virus (RSV) infection in infants, we performed a systems-level study of RSV pathophysiology, incorporating high-throughput measurements of the peripheral innate and adaptive immune systems and the airway epithelium and microbiota. Specifically, we developed and employed a novel multi-omic data integration method based on multilayered principal component analysis, penalized regression, and feature weight back-propagation. Our novel approach enabled us to identify cell type specific and shared cellular pathways associated with RSV severity. Of particular interest was the association between RSV severity, activation of pathways controlling Th17 and acute phase response signaling, and inhibition of B cell receptor signaling, which were present in both airway and immune cells. These data identify specific aspects of dysregulation between the humoral and mucosal response to RSV that may play a critical role in determining illness severity.

scholarly journals Fcγ Receptor IIa (FCGR2A) Polymorphism Is Associated With Severe Respiratory Syncytial Virus Disease in Argentinian Infants

2020 ◽  
Vol 10 ◽  
Author(s):  
María Pía Holgado ◽  
Silvina Raiden ◽  
Inés Sananez ◽  
Vanesa Seery ◽  
Leonardo De Lillo ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Virus Disease ◽  
Severe Disease ◽  
Critical Role ◽  
Fcγ Receptor ◽  
Factors Associated ◽  
Severe Group ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
The Relationship

BackgroundMost patients with respiratory syncytial virus (RSV) infection requiring hospitalization have no risk factors for severe disease. Genetic variation in the receptor for the Fc portion of IgG (FcγR) determines their affinity for IgG subclasses driving innate and adaptive antiviral immunity. We investigated the relationship between FcγRIIa-H131R polymorphism and RSV disease.MethodsBlood samples were collected from 182 infants ≤24-month-old (50 uninfected, 114 RSV-infected with moderate course and 18 suffering severe disease). FcγRIIa-H131R SNP genotypic frequencies (HH, HR, RR) and anti-RSV IgG1, IgG2 and IgG3 levels were studied.ResultsGenotypic frequencies for FcγRIIa-H131R SNP were comparable between uninfected and RSV-infected infants. In contrast, we found a significant higher frequency of HH genotype in severe RSV-infected children compared to moderate patients. Among severe group, HH infants presented more factors associated to severity than HR or RR patients did. Furthermore, compared to moderate RSV-infected infants, severe patients showed higher levels of anti-RSV IgG1 and IgG3.ConclusionsWe found an association between an FcγRIIa (H131) polymorphism and severe RSV disease, which points towards a critical role for interactions between FcγRs and immune complexes in RSV pathogenesis. This genetic factor could also predict the worse outcome and identify those infants at risk during hospitalization.

Osteopontin (OPN) Plays a Critical Role in Respiratory Syncytial Virus (RSV) Infection

2015 ◽  
Vol 135 (2) ◽  
pp. AB109
Author(s):  
Viviana P. Sampayo-Escobar ◽  
Terianne M. Wong ◽  
Sandhya Boyapalle ◽  
Raminder Bedi ◽  
Subhra Mohapatra ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Critical Role ◽  
Rsv Infection ◽  
Syncytial Virus

scholarly journals Respiratory Syncytial Virus-Mediated NF-κB p65 Phosphorylation at Serine 536 Is Dependent on RIG-I, TRAF6, and IKKβ

2010 ◽  
Vol 84 (14) ◽  
pp. 7267-7277 ◽  
Author(s):  
Fabrice Yoboua ◽  
Alexis Martel ◽  
Annick Duval ◽  
Espérance Mukawera ◽  
Nathalie Grandvaux
Keyword(s):  
Respiratory Syncytial Virus ◽  
Critical Role ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Proinflammatory Response ◽  
Cytokines And Chemokines ◽  
Upstream Regulator ◽  
Rsv Infection ◽  
Oxidase Enzyme ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) is the etiological agent of acute respiratory diseases, such as bronchiolitis and pneumonia. The exacerbated production of proinflammatory cytokines and chemokines in the airways in response to RSV is an important pillar in the development of these pathologies. As such, a keen understanding of the mechanisms that modulate the inflammatory response during RSV infection is of pivotal importance to developing effective treatment. The NF-κB transcription factor is a major regulator of proinflammatory cytokine and chemokine genes. However, RSV-mediated activation of NF-κB is far from characterized. We recently demonstrated that aside from the well-characterized IκBα phosphorylation and degradation, the phosphorylation of p65 at Ser536 is an essential event regulating the RSV-mediated NF-κB-dependent promoter transactivation. In the present study, using small interfering RNA and pharmacological inhibitors, we now demonstrate that RSV sensing by the RIG-I cytoplasmic receptor triggers a signaling cascade involving the MAVS and TRAF6 adaptors that ultimately leads to p65ser536 phosphorylation by the IKKβ kinase. In a previous study, we highlighted a critical role of the NOX2-containing NADPH oxidase enzyme as an upstream regulator of both the IκBαSer32 and p65Ser536 in human airway epithelial cells. Here, we demonstrate that inhibition of NOX2 significantly decreases IKKβ activation. Taken together, our data identify a new RIG-I/MAVS/TRAF6/IKKβ/p65Ser536 pathway placed under the control of NOX2, thus characterizing a novel regulatory pathway involved in NF-κB-driven proinflammatory response in the context of RSV infection.

scholarly journals NLRP3-Inflammasome Inhibition during Respiratory Virus Infection Abrogates Lung Immunopathology and Long-Term Airway Disease Development

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 692
Author(s):  
Carrie-Anne Malinczak ◽  
Charles F. Schuler ◽  
Angela J. Duran ◽  
Andrew J. Rasky ◽  
Mohamed M. Mire ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Severe Disease ◽  
Critical Role ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Increased Risk ◽  
Rsv Infection ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) infects most infants by two years of age. It can cause severe disease leading to an increased risk of developing asthma later in life. Previously, our group has shown that RSV infection in mice and infants promotes IL-1β production. Here, we characterized the role of NLRP3-Inflammasome activation during RSV infection in adult mice and neonates. We observed that the inhibition of NLRP3 activation using the small molecule inhibitor, MCC950, or in genetically modified NLRP3 knockout (Nlrp3−/−) mice during in vivo RSV infection led to decreased lung immunopathology along with a reduced expression of the mucus-associated genes and reduced production of innate cytokines (IL-1β, IL-33 and CCL2) linked to severe RSV disease while leading to significant increases in IFN-β. NLRP3-inflammasome inhibition or deletion diminished Th2 cytokines and inflammatory cell infiltration into the lungs. Furthermore, NLRP3 inhibition or deletion during early-life RSV infection led to reducing viral-exacerbated allergic response in a mouse model of RSV-induced allergy exacerbation. Here, we demonstrated the critical role of NLRP3-inflammasome activation in RSV immunopathology and the related long-term airway alteration. Moreover, these findings suggest the NLRP3-inflammasome as a potential therapeutic target to attenuate severe RSV disease and limit childhood asthma development.

scholarly journals IFN-γ Attenuates Eosinophilic Inflammation but Is Not Essential for Protection against RSV-Enhanced Asthmatic Comorbidity in Adult Mice

Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 147
Author(s):  
Abenaya Muralidharan ◽  
Md Bashir Uddin ◽  
Christopher Bauer ◽  
Wenzhe Wu ◽  
Xiaoyong Bao ◽  
...  
Keyword(s):  
Critical Role ◽  
Lung Damage ◽  
Eosinophil Infiltration ◽  
Severe Illness ◽  
Eosinophilic Inflammation ◽  
Adult Mice ◽  
Helper Cell Type ◽  
Rsv Infection ◽  
Ifn Γ ◽  
Syncytial Virus

The susceptibility to respiratory syncytial virus (RSV) infection in early life has been associated with a deficient T-helper cell type 1 (Th1) response. Conversely, healthy adults generally do not exhibit severe illness from RSV infection. In the current study, we investigated whether Th1 cytokine IFN-γ is essential for protection against RSV and RSV-associated comorbidities in adult mice. We found that, distinct from influenza virus, prior RSV infection does not induce significant IFN-γ production and susceptibility to secondary Streptococcus pneumoniae infection in adult wild-type (WT) mice. In ovalbumin (OVA)-induced asthmatic mice, RSV super-infection increases airway neutrophil recruitment and inflammatory lung damage but has no significant effect on OVA-induced eosinophilia. Compared with WT controls, RSV infection of asthmatic Ifng−/− mice results in increased airway eosinophil accumulation. However, a comparable increase in eosinophilia was detected in house dust mite (HDM)-induced asthmatic Ifng−/− mice in the absence of RSV infection. Furthermore, neither WT nor Ifng−/− mice exhibit apparent eosinophil infiltration during RSV infection alone. Together, these findings indicate that, despite its critical role in limiting eosinophilic inflammation during asthma, IFN-γ is not essential for protection against RSV-induced exacerbation of asthmatic inflammation in adult mice.

Strategies for Reducing the Risk of Respiratory Syncytial Virus Infection in Infants and Young Children: A Canadian Nurses’ Perspective

2012 ◽  
Vol 31 (6) ◽  
pp. 357-368 ◽  
Author(s):  
Marianne Bracht ◽  
Debbie Basevitz ◽  
Marilyn Cranis ◽  
Rose Paulley ◽  
Bosco Paes
Keyword(s):  
Health Care ◽  
Respiratory Syncytial Virus ◽  
Young Children ◽  
Health Care Providers ◽  
Critical Role ◽  
Care Providers ◽  
Adverse Health Outcomes ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Infants And Young Children

Respiratory syncytial virus (RSV) infections are prevalent globally and can cause substantial morbidity in infants and young children. The virus is easily transmitted by direct hand-to-hand contact and can lead to serious respiratory disease and hospitalization, particularly in premature infants and children with certain medical conditions. Educating families with young children, especially those in remote rural regions, regarding the potential adverse health outcomes of RSV infection and measures to reduce the risk of transmitting or acquiring RSV has been a key focus of the health care system in Canada. Geographic, cultural, and socioeconomic factors present formidable challenges to the execution of this endeavor. Therefore, it is critical to develop and systematically implement effective educational programs for both families and health care providers. In Canada, nurses play a critical role in education and counseling. In this review, we share our perspectives and suggest empirical practices that may be applicable worldwide.

Elderly fall risk prediction based on a physiological profile approach using artificial neural networks

2016 ◽  
Vol 24 (4) ◽  
pp. 410-418 ◽  
Author(s):  
Jafar Razmara ◽  
Mohammad Hassan Zaboli ◽  
Hadi Hassankhani
Keyword(s):  
Neural Network ◽  
Experimental Data ◽  
At Risk ◽  
Fall Risk ◽  
Learning Algorithm ◽  
Critical Role ◽  
Back Propagation ◽  
Principal Component ◽  
Physiological Profile ◽  
Profile Approach

Falls play a critical role in older people’s life as it is an important source of morbidity and mortality in elders. In this article, elders fall risk is predicted based on a physiological profile approach using a multilayer neural network with back-propagation learning algorithm. The personal physiological profile of 200 elders was collected through a questionnaire and used as the experimental data for learning and testing the neural network. The profile contains a series of simple factors putting elders at risk for falls such as vision abilities, muscle forces, and some other daily activities and grouped into two sets: psychological factors and public factors. The experimental data were investigated to select factors with high impact using principal component analysis. The experimental results show an accuracy of ≈90 percent and ≈87.5 percent for fall prediction among the psychological and public factors, respectively. Furthermore, combining these two datasets yield an accuracy of ≈91 percent that is better than the accuracy of single datasets. The proposed method suggests a set of valid and reliable measurements that can be employed in a range of health care systems and physical therapy to distinguish people who are at risk for falls.

scholarly journals Microbiome-Transcriptome Interactions Related to Severity of Respiratory Syncytial Virus Infection

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Abhijeet R. Sonawane ◽  
Liang Tian ◽  
Chin-Yi Chu ◽  
Xing Qiu ◽  
Lu Wang ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Principal Component ◽  
Linear Interpolation ◽  
Integrative Analysis ◽  
Host Immune System ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Infections ◽  
The Impact

Abstract Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections and hospital visits during infancy and childhood. Although risk factors for RSV infection have been identified, the role of microbial species in the respiratory tract is only partially known. We aimed to understand the impact of interactions between the nasal microbiome and host transcriptome on the severity and clinical outcomes of RSV infection. We used 16 S rRNA sequencing to characterize the nasal microbiome of infants with RSV infection. We used RNA sequencing to interrogate the transcriptome of CD4+ T cells obtained from the same set of infants. After dimension reduction through principal component (PC) analysis, we performed an integrative analysis to identify significant co-variation between microbial clade and gene expression PCs. We then employed LIONESS (Linear Interpolation to Obtain Network Estimates for Single Samples) to estimate the clade-gene association patterns for each infant. Our network-based integrative analysis identified several clade-gene associations significantly related to the severity of RSV infection. The microbial taxa with the highest loadings in the implicated clade PCs included Moraxella, Corynebacterium, Streptococcus, Haemophilus influenzae, and Staphylococcus. Interestingly, many of the genes with the highest loadings in the implicated gene PCs are encoded in mitochondrial DNA, while others are involved in the host immune response. This study on microbiome-transcriptome interactions provides insights into how the host immune system mounts a response against RSV and specific infectious agents in nasal microbiota.

scholarly journals Treatment with Anti-LFA-1 Delays the CD8+ Cytotoxic-T-Lymphocyte Response and Viral Clearance in Mice with Primary Respiratory Syncytial Virus Infection

2004 ◽  
Vol 78 (6) ◽  
pp. 3014-3023 ◽  
Author(s):  
John A. Rutigliano ◽  
Teresa R. Johnson ◽  
Tonya N. Hollinger ◽  
Julie E. Fischer ◽  
Sandra Aung ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
Cytolytic Activity ◽  
Lymphocyte Function ◽  
Lymphocyte Migration ◽  
Cell Surface Molecule ◽  
Rsv Infection ◽  
Syncytial Virus

ABSTRACT Cytotoxic T lymphocytes (CTLs) play an important role in the immune response against respiratory syncytial virus (RSV) infection. The cell surface molecule lymphocyte function-associated antigen 1 (LFA-1) is an important contributor to CTL activation, CTL-mediated direct cell lysis, and lymphocyte migration. In an attempt to determine the role of LFA-1 during RSV infection, we treated BALB/c mice with monoclonal antibodies to LFA-1 at days −1, +1, and +4 relative to primary RSV infection. Anti-LFA-1 treatment during primary RSV infection led to reduced illness and delayed clearance of virus-infected cells. CTLs from RSV-infected mice that were treated with anti-LFA-1 exhibited diminished cytolytic activity and reduced gamma interferon production. In addition, studies with BrdU (5-bromo-2′-deoxyuridine)- and CFSE [5-(and 6)-carboxyfluorescein diacetate succinimidyl ester]-labeled lymphocytes showed that anti-LFA-1 treatment led to delayed proliferation during RSV infection. These results indicate that LFA-1 plays a critical role in the initiation of the immune response to RSV infection by facilitating CTL activation. These results may prove useful in the development of new therapies to combat RSV infection or other inflammatory diseases.

Sign in / Sign up

Export Citation Format

Share Document