scholarly journals Respiratory syncytial virus is associated with an inflammatory response in lungs and architectural remodeling of lung-draining lymph nodes of newborn lambs

2011 ◽  
Vol 300 (1) ◽  
pp. L12-L24 ◽  
Author(s):  
Fatoumata B. Sow ◽  
Jack M. Gallup ◽  
Alicia Olivier ◽  
Subramaniam Krishnan ◽  
Andriani C. Patera ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Lymph Nodes ◽  
Transcriptional Response ◽  
Lymphoid Hyperplasia ◽  
Interferon Response ◽  
Lung Macrophage ◽  
Rsv Infection ◽  
Tracheobronchial Lymph Nodes ◽  
Syncytial Virus ◽  
Draining Lymph Nodes

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in children worldwide. The understanding of neonatal RSV pathogenesis depends on using an animal model that reproduces neonatal RSV disease. Previous studies from us and others demonstrated that the neonatal lamb model resembles human neonatal RSV infection. Here, we provide an extensive and detailed characterization of the histopathology, viral load, cellular infiltration, and cytokine production in lungs and tracheobronchial lymph nodes of lambs inoculated with human RSV strain A2 over the course of infection. In the lung, RSV titers were low at day 3 postinfection, increased significantly by day 6, and decreased to baseline levels at day 14. Infection in the lung was associated with an accumulation of macrophages, CD4+ and CD8+ T cells, and a transcriptional response of genes involved in inflammation, chemotaxis, and interferon response, characterized by increased IFNγ, IL-8, MCP-1, and PD-L1, and decreased IFNβ, IL-10, and TGF-β. Laser capture microdissection studies determined that lung macrophage-enriched populations were the source of MCP-1 but not IL-8. Immunoreactivity to caspase 3 occurred within bronchioles and alveoli of day 6-infected lambs. In lung-draining lymph nodes, RSV induced lymphoid hyperplasia, suggesting an ability of RSV to enhance lymphocytic proliferation and differentiation pathways. This study suggests that, in lambs with moderate clinical disease, RSV enhances the activation of caspase cell death and Th1-skewed inflammatory pathways, and complements previous observations that emphasize the role of inflammation in the pathogenesis of RSV disease.

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 Pulmonary mesenchymal stem cells are engaged in distinct steps of host response to respiratory syncytial virus infection

2021 ◽  
Vol 17 (7) ◽  
pp. e1009789
Author(s):  
Melanie Brügger ◽  
Thomas Démoulins ◽  
G. Tuba Barut ◽  
Beatrice Zumkehr ◽  
Blandina I. Oliveira Esteves ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Lung Injury ◽  
Cell Function ◽  
Transcriptional Response ◽  
Therapeutic Implications ◽  
Repair Mechanisms ◽  
Inflammatory Phenotype ◽  
Rsv Infection ◽  
Syncytial Virus

Lung-resident (LR) mesenchymal stem and stromal cells (MSCs) are key elements of the alveolar niche and fundamental regulators of homeostasis and regeneration. We interrogated their function during virus-induced lung injury using the highly prevalent respiratory syncytial virus (RSV) which causes severe outcomes in infants. We applied complementary approaches with primary pediatric LR-MSCs and a state-of-the-art model of human RSV infection in lamb. Remarkably, RSV-infection of pediatric LR-MSCs led to a robust activation, characterized by a strong antiviral and pro-inflammatory phenotype combined with mediators related to T cell function. In line with this, following in vivo infection, RSV invades and activates LR-MSCs, resulting in the expansion of the pulmonary MSC pool. Moreover, the global transcriptional response of LR-MSCs appears to follow RSV disease, switching from an early antiviral signature to repair mechanisms including differentiation, tissue remodeling, and angiogenesis. These findings demonstrate the involvement of LR-MSCs during virus-mediated acute lung injury and may have therapeutic implications.

scholarly journals Pulmonary mesenchymal stem cells are engaged in distinct steps of host response to respiratory syncytial virus infection

2021 ◽  
Author(s):  
Melanie Brugger ◽  
Thomas Demoulins ◽  
G. Tuba Barut ◽  
Beatrice Zumkehr ◽  
Blandina Oliveira Esteves ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Lung Injury ◽  
Cell Function ◽  
Transcriptional Response ◽  
Therapeutic Implications ◽  
Repair Mechanisms ◽  
Inflammatory Phenotype ◽  
Rsv Infection ◽  
Syncytial Virus

Lung-resident (LR) mesenchymal stem and stromal cells (MSCs) are key elements of the alveolar niche and fundamental regulators of homeostasis and regeneration. We interrogated their function during virus-induced lung injury using the highly prevalent respiratory syncytial virus (RSV) which causes severe outcomes in infants. We applied complementary approaches with primary pediatric LR-MSCs and a state-of-the-art model of human RSV infection in lamb. Remarkably, RSV-infection of pediatric LR-MSCs led to a robust activation, characterized by a strong antiviral and pro-inflammatory phenotype combined with mediators related to T cell function. In line with this, following in vivo infection, RSV invades and activates LR-MSCs, resulting in the expansion of the pulmonary MSC pool. Moreover, the global transcriptional response of LR-MSCs appears to follow RSV disease, switching from an early antiviral signature to repair mechanisms including differentiation, tissue remodeling, and angiogenesis. These findings demonstrate the involvement of LR-MSCs during virus-mediated acute lung injury and may have therapeutic implications.

scholarly journals Identification of erythroid cell positive blood transcriptome phenotypes associated with severe respiratory syncytial virus infection

2019 ◽  
Author(s):  
Darawan Rinchai ◽  
Matthew B Altman ◽  
Oceane Konza ◽  
Signe Hässler ◽  
Federica Martina ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Respiratory Syncytial Virus ◽  
Meta Analysis ◽  
Host Responses ◽  
Interferon Response ◽  
Erythroid Cell ◽  
Severe Respiratory Syncytial Virus ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Blood Transcriptome

ABSTRACTBiomarkers to assess the severity of acute respiratory syncytial virus (RSV) infection are needed. We conducted a meta-analysis of 490 unique profiles from six public RSV blood transcriptome datasets. A repertoire of 382 well-characterized transcriptional modules was used to define dominant host responses to RSV infection. The consolidated RSV cohort was stratified according to four traits: “interferon response” (IFN), “neutrophil-driven inflammation” (Infl), “cell cycle” (CC), and “erythrocytes” (Ery). Eight prevalent blood transcriptome phenotypes were thus identified. Among those three Ery+ phenotypes comprised higher proportions of patients requiring intensive care. We posit that the erythrocyte module is linked to an overabundance of immunosuppressive erythroid cells that might underlie progression to severe RSV infection. These findings outline potential priority areas for biomarker development and investigations into the immune biology of RSV infection. The approach that was employed here will also permit to delineate prevalent blood transcriptome phenotypes in other settings.

scholarly journals Evaluation of the Safety and Immune Efficacy of Recombinant Human Respiratory Syncytial Virus Strain Long Live Attenuated Vaccine Candidates

2021 ◽  
Author(s):  
Li-Nan Wang ◽  
Xiang-Lei Peng ◽  
Min Xu ◽  
Yuan-Bo Zheng ◽  
Yue-Ying Jiao ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Gene Deletion ◽  
Human Respiratory Syncytial Virus ◽  
Temperature Sensitive ◽  
T7 Promoter ◽  
Vaccine Candidates ◽  
Rsv Infection ◽  
Syncytial Virus

AbstractHuman respiratory syncytial virus (RSV) infection is the leading cause of lower respiratory tract illness (LRTI), and no vaccine against LRTI has proven to be safe and effective in infants. Our study assessed attenuated recombinant RSVs as vaccine candidates to prevent RSV infection in mice. The constructed recombinant plasmids harbored (5′ to 3′) a T7 promoter, hammerhead ribozyme, RSV Long strain antigenomic cDNA with cold-passaged (cp) mutations or cp combined with temperature-sensitive attenuated mutations from the A2 strain (A2cpts) or further combined with SH gene deletion (A2cptsΔSH), HDV ribozyme (δ), and a T7 terminator. These vectors were subsequently co-transfected with four helper plasmids encoding N, P, L, and M2-1 viral proteins into BHK/T7-9 cells, and the recovered viruses were then passaged in Vero cells. The rescued recombinant RSVs (rRSVs) were named rRSV-Long/A2cp, rRSV-Long/A2cpts, and rRSV-Long/A2cptsΔSH, respectively, and stably passaged in vitro, without reversion to wild type (wt) at sites containing introduced mutations or deletion. Although rRSV-Long/A2cpts and rRSV-Long/A2cptsΔSH displayed  temperature-sensitive (ts) phenotype in vitro and in vivo, all rRSVs were significantly attenuated in vivo. Furthermore, BALB/c mice immunized with rRSVs produced Th1-biased immune response, resisted wtRSV infection, and were free from enhanced respiratory disease. We showed that the combination of ΔSH with attenuation (att) mutations of cpts contributed to improving att phenotype, efficacy, and gene stability of rRSV. By successfully introducing att mutations and SH gene deletion into the RSV Long parent and producing three rRSV strains, we have laid an important foundation for the development of RSV live attenuated vaccines.

scholarly journals Respiratory Syncytial Virus Immunoprophylaxis with Palivizumab: 12-Year Observational Study of Usage and Outcomes in Canada

2021 ◽  
Author(s):  
Ian Mitchell ◽  
Abby Li ◽  
Candice L. Bjornson ◽  
Krista L. Lanctot ◽  
Bosco A. Paes ◽  
...  
Keyword(s):  
Risk Factors ◽  
Respiratory Syncytial Virus ◽  
Burden Of Illness ◽  
Respiratory Illness ◽  
Smoking Exposure ◽  
Key Points ◽  
Rsv Infection ◽  
History Of ◽  
Syncytial Virus ◽  
Airway Anomalies

Objective This study aimed to evaluate palivizumab (PVZ) use, trends in indications, and outcomes of respiratory illness hospitalizations (RIH) and respiratory syncytial virus hospitalizations (RSVH). Study Design It involves a large, Canadian prospective (2005–2017) observational multicenter study of children at high risk for RSV infection. Results A total of 25,003 infants (56.3% male) were enrolled at 32 sites; 109,579 PVZ injections were administered. Indications included: prematurity (63.3%); “miscellaneous” (17.8%); hemodynamically significant congenital heart disease (10.5%); bronchopulmonary dysplasia/chronic lung disease (8.4%). The “miscellaneous” group increased over time (4.4% in 2005–2006 to 22.5% in 2016–2017) and included: trisomy 21, airway anomalies, pulmonary disorders, cystic fibrosis, neurological impairments, immunocompromised, cardiac aged >2 years, multiple conditions, and a residual “unclassified” group. Adherence measured by expected versus actual doses plus correct interdose interval was 64.7%. A total of 2,054 RIH occurred (6.9%); 198 (9.6%) required intubation. Three hundred thirty-seven hospitalized children were RSV-positive (overall RSVH 1.6%). Risk factors for RSVH included having siblings, attending daycare, family history of atopy, smoking exposure, and crowded household. Infants with 5 risk factors were 9.0 times (95% CI or confidence interval 4.4–18.2; p < 0.0005) more likely to have RSVH than infants without risk factors. Three adverse events occurred; none were fatal. Conclusion Results are relevant to both clinicians and decision-makers. We confirmed the safety of PVZ. Use of PVZ increased steadily for children with miscellaneous conditions and medical complexity. Medical and social factors pose a risk for severe RIH and RSVH with accompanying burden of illness. A vaccine that protects against RSV is urgently required. Key Points

scholarly journals Respiratory syncytial virus in severe lower respiratory infections in previously healthy young Ethiopian infants

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Abate Yeshidinber Weldetsadik ◽  
Frank Riedel
Keyword(s):  
Respiratory Syncytial Virus ◽  
Rainy Season ◽  
Clinical Laboratory ◽  
Respiratory Infections ◽  
Clinical Parameter ◽  
Imaging Data ◽  
Chi Square ◽  
Young Infants ◽  
Rsv Infection ◽  
Syncytial Virus

Abstract Background Respiratory Syncytial Virus (RSV) is the commonest cause of acute lower respiratory infections (ALRI) in infants. However, the burden of RSV is unknown in Ethiopia. We aimed to determine the prevalence, seasonality and predictors of RSV infection in young infants with ALRI for the first time in Ethiopia. Methods We performed RSV immuno-chromatographic assay from nasopharyngeal swabs of infants, 29 days to 6 months of age. We included the first 10 eligible infants in each month from June 2018 to May 2019 admitted in a tertiary pediatric center. Clinical, laboratory and imaging data were also collected, and chi-square test and regression were used to assess associated factors with RSV infection. Results Among a total of 117 study children, 65% were male and mean age was 3 months. Bronchiolitis was the commonest diagnosis (49%). RSV was isolated from 26 subjects (22.2%) of all ALRI, 37% of bronchiolitis and 11% of pneumonia patients. Although RSV infection occurred year round, highest rate extended from June to November. No clinical or laboratory parameter predicted RSV infection and only rainy season (Adjusted Odds Ratio (AOR) 10.46 [95%. C.I. 1.95, 56.18]) was independent predictor of RSV infection. Conclusions RSV was isolated in a fifth of young infants with severe ALRI, mostly in the rainy season. Diagnosis of RSV infection in our setting require specific tests as no clinical parameter predicted RSV infection. Since RSV caused less than a quarter of ALRI in our setting, the other causes should be looked for in future studies.

scholarly journals Inhibitory Effect of Sargassum fusiforme and Its Components on Replication of Respiratory Syncytial Virus In Vitro and In Vivo

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 548
Author(s):  
Kiramage Chathuranga ◽  
Asela Weerawardhana ◽  
Niranjan Dodantenna ◽  
Lakmal Ranathunga ◽  
Won-Kyung Cho ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Antiviral Agent ◽  
Active Components ◽  
Sargassum Fusiforme ◽  
Antiviral Effects ◽  
Improve Life Expectancy ◽  
Rsv Infection ◽  
Syncytial Virus

Sargassum fusiforme, a plant used as a medicine and food, is regarded as a marine vegetable and health supplement to improve life expectancy. Here, we demonstrate that S. fusiforme extract (SFE) has antiviral effects against respiratory syncytial virus (RSV) in vitro and in vivo mouse model. Treatment of HEp2 cells with a non-cytotoxic concentration of SFE significantly reduced RSV replication, RSV-induced cell death, RSV gene transcription, RSV protein synthesis, and syncytium formation. Moreover, oral inoculation of SFE significantly improved RSV clearance from the lungs of BALB/c mice. Interestingly, the phenolic compounds eicosane, docosane, and tetracosane were identified as active components of SFE. Treatment with a non-cytotoxic concentration of these three components elicited similar antiviral effects against RSV infection as SFE in vitro. Together, these results suggest that SFE and its potential components are a promising natural antiviral agent candidate against RSV infection.

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