scholarly journals Infant baboons infected with respiratory syncytial virus develop clinical and pathological changes that parallel those of human infants

2013 ◽  
Vol 304 (8) ◽  
pp. L530-L539 ◽  
Author(s):  
James F. Papin ◽  
Roman F. Wolf ◽  
Stanley D. Kosanke ◽  
Justin D. Jenkins ◽  
Sara N. Moore ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Alveolar Epithelium ◽  
Inflammatory Cells ◽  
The United States ◽  
Pathological Changes ◽  
Papio Anubis ◽  
Human Infants ◽  
Infected Infant ◽  
Rsv Infection ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) infection of the lower respiratory tract is the leading cause of respiratory failure among infants in the United States of America and annually results in >300,000 deaths worldwide. Despite the importance of RSV, there is no licensed vaccine, and no specific form of therapy. This is largely due to the absence of an appropriate animal model for the evaluation of vaccines and therapeutic agents. We inoculated anesthetized infant (4 wk) baboons ( Papio anubis) with a human strain of RSV intranasally or intratracheally. Baboons were monitored daily for clinical changes. Anesthetized baboons were intubated at various intervals, and bronchoalveolar lavage (BAL) was performed for viral culture and determination of leukocyte counts. Sham-infected baboons served as controls. Necropsies were performed on infected baboons on days 1, 3, 5, 8, or 13 after inoculation, with pathological analysis and immunohistochemical staining of lung tissues to detect RSV antigen. Infected baboons developed tachypnea and reduced oxygenation peaking from 4 to 8 days after infection and persisting for ≥14 days. Virus was recoverable in BAL fluid up to 8 days following infection. Necropsy revealed intense interstitial pneumonia, sloughing of the bronchiolar epithelium, and obstruction of the bronchiolar lumen with inflammatory cells and sloughed epithelial cells. RSV antigen was identified in bronchiolar and alveolar epithelium. We conclude that RSV-infected infant baboons develop clinical and pathological changes that parallel those observed in human infants with RSV infection. The infant baboon represents a much-needed model for studying the pathogenesis of RSV infection and evaluating antivirals and vaccines.

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.

scholarly journals Respiratory Syncytial Virus Prophylaxis in Special Populations: Is it Something Worth Considering in Cystic Fibrosis and Immunosuppression?

2011 ◽  
Vol 16 (2) ◽  
pp. 77-86
Author(s):  
William A. Prescott ◽  
David J. Hutchinson
Keyword(s):  
Respiratory Syncytial Virus ◽  
Cost Benefit ◽  
The United States ◽  
Randomized Controlled ◽  
Increased Risk ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
The Cost ◽  
Infant Hospitalization ◽  
Infants And Young Children

ABSTRACT Respiratory syncytial virus (RSV) bronchiolitis is the leading cause of infant hospitalization in the United States. Prophylaxis with palivizumab is effective in reducing RSV hospitalizations in premature infants and in infants or children with chronic lung disease or congenital heart disease. Patients with CF or those who are immunocompromised may be at increased risk for RSV infection–related complications; hence, prophylaxis may prove beneficial to these populations. The extent of palivizumab use in the CF and immunocompromised populations is variable. Palivizumab appears to be safe and may be effective in infants and young children with CF and immunocompromise. However, well-designed, randomized, controlled trials published in peer-reviewed journals are lacking, and its routine use can therefore not be recommended at this time. If used in patients with CF or those who are immunocompromised, RSV prophylaxis should be restricted to peak outbreak months in order to optimize the cost benefit of palivizumab.

scholarly journals Long-chain non-coding RNA n337374 relieves symptoms of respiratory syncytial virus-induced asthma by inhibiting dendritic cell maturation via the CD86 and ERK pathway

2021 ◽  
Vol 49 (3) ◽  
pp. 100-107
Author(s):  
Shuning Sun ◽  
Ming Yao ◽  
Lifen Yuan ◽  
Jianou Qiao
Keyword(s):  
Respiratory Syncytial Virus ◽  
Lung Function ◽  
Mouse Model ◽  
Inflammatory Cells ◽  
Airway Epithelial Cells ◽  
Erk Pathway ◽  
Airway Epithelial ◽  
Pathological Changes ◽  
Syncytial Virus ◽  
Long Chain

Background: In this study, we investigated the relationship between long-chain non-coding RNAs (lncRNAs) and respiratory syncytial virus (RSV)- exacerbated asthma. Methods: Transcriptome microarray was used to detect differentially expressed lncRNAs in dendritic cells (DCs) co-cultured with RSV-infected human airway epithelial cells and DCs infected with RSV. The identified downregulation of lncRNA n337374 was validated using fluorescence RT-qPCR. LncRNA n337374-overexpressing DCs and RSV-exacerbated asthmatic mouse models were established. Airway hyperreactivity and bronchoalveolar lavage fluid (BALF) were examined, and pathological changes in lung tissues were observed in mice. Surface molecules in DCs were detected by flow cytometry and RT-qPCR and the expression of CD86 and mitogen-activated protein kinases was determined by western blot. Results: In an RSV-exacerbated asthmatic mouse model, the airway wall was thickened, luminal stenosis was observed, a large number of inflammatory cells were infiltrated in the lung tissue, lung function was impaired, and counts of inflammatory cells in the BALF were increased. The overexpression of lncRNA n337374 ameliorated these pathological changes and improved impaired lung function and inflammation in an asthmatic mouse model. In DCs co-cultured with RSV-infected human airway epithelial cells, CD86 expression was promoted and ERK was markedly phosphorylated. When lncRNA n337374-overexpressing DCs were used in the co-cultures, the expression of CD86 and phosphorylated ERK was decreased. Conclusion: The results suggest that lncRNA n337374 overexpression may suppress DC maturation by downregulating the CD86 and ERK pathway, subsequently relieving the symptoms of RSV-induced asthma. LncRNA n337374 may be a promising target in the treatment of RSV infection-induced asthma.

scholarly journals Severe Morbidity and Short- and Mid- to Long-term Mortality in Older Adults Hospitalized with Respiratory Syncytial Virus Infection

2020 ◽  
Vol 222 (8) ◽  
pp. 1298-1310 ◽  
Author(s):  
Hung Fu Tseng ◽  
Lina S Sy ◽  
Bradley Ackerson ◽  
Zendi Solano ◽  
Jeff Slezak ◽  
...  
Keyword(s):  
Older Adults ◽  
Respiratory Syncytial Virus ◽  
Clinical Epidemiology ◽  
Ventilatory Support ◽  
The United States ◽  
Rsv Infection ◽  
Hospitalized Older Adults ◽  
Syncytial Virus ◽  
Long Term Mortality

Abstract Background We describe the clinical epidemiology and outcomes among a large cohort of older adults hospitalized with respiratory syncytial virus (RSV) infection in the United States. Methods Hospitalized adults aged ≥60 years who tested positive for RSV between 1 January 2011 and 30 June 2015 were identified from Kaiser Permanente Southern California. Patient-level demographics, comorbidities, clinical presentation, utilization, complications, and mortality were evaluated. Results There were 664 patients hospitalized with RSV (61% female, 64% aged ≥75 years). Baseline chronic diseases were prevalent (all >30%); 66% developed pneumonia, 80% of which were radiographically confirmed. Very severe tachypnea (≥26 breaths/minute) was common (56%); 21% required ventilator support and 18% were admitted to intensive care unit. Mortality during hospitalization was 5.6% overall (4.6% in 60–74 year olds and 6.1% in ≥75 year olds). Cumulative mortality within 1, 3, 6, and 12 months of admission was 8.6%, 12.3%, 17.2%, and 25.8%, respectively. Conclusion RSV infection in hospitalized older adults often manifested as severe, life-threatening lower respiratory tract illness with high rates of pneumonia, requirement for ventilatory support, and short- and long-term mortality. Increased recognition of the substantial RSV disease burden in adults will be important in evaluation and use of urgently needed interventions.

scholarly journals The Prevention of Respiratory Syncytial Virus Infection in Children: Focus on Palivizumab

2009 ◽  
Vol 1 ◽  
pp. CMT.S2072
Author(s):  
Michael E. Speer ◽  
Amy B. Good
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Infections ◽  
The United States ◽  
Humanized Monoclonal Antibody ◽  
Post Marketing ◽  
Rsv Infection ◽  
Upper Respiratory ◽  
Syncytial Virus ◽  
One Year ◽  
High Risk Infants

Recurrent upper respiratory infections caused by respiratory syncytial virus (RSV) and other respiratory viruses occur throughout life. During the first 2 years of life, RSV infected children have up to a 40% risk of a lower respiratory tract infection (LRTI). In turn LRTI, including bronchiolitis, due to RSV is the most common cause of hospitalization among infants less than one year of age. While mortality from RSV infection has fallen over the last 2 decades, approximately 400-500 deaths occur annually in the United States again primarily in infants less than 1 year of age. Palivizumab, a humanized monoclonal antibody, has been shown to reduce the risk of hospitalization in high risk infants if given monthly during RSV season. Post marketing safety surveillance originating from a variety of sources, mostly active surveillance, has confirmed the prelicensure safety profile of palivizumab. Other than very rare anaphylactic reactions (<1/100000), no significant adverse reactions have been noted.

scholarly journals 2797. Rates of Respiratory Syncytial Virus (RSV) Infection among Hospitalized Adults by Congestive Heart Failure Status—United States, 2015–2017

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S988-S989
Author(s):  
Stephanie A Kujawski ◽  
Gayle Langley ◽  
Gayle Langley ◽  
Evan J Anderson ◽  
Ann Thomas ◽  
...  
Keyword(s):  
United States ◽  
Heart Failure ◽  
Congestive Heart Failure ◽  
Respiratory Syncytial Virus ◽  
Catchment Area ◽  
The United States ◽  
Population Based ◽  
County Level ◽  
Rsv Infection ◽  
Syncytial Virus

Abstract Background Respiratory syncytial virus (RSV) can cause severe disease in older adults and adults with cardiopulmonary conditions, such as congestive heart failure (CHF). RSV vaccines in development may target adults based on age or medical conditions. We assessed rates of RSV infection in hospitalized adults by CHF status using RSV surveillance conducted through the Centers for Disease Control and Prevention’s Emerging Infections Program, a population-based platform in the United States Methods RSV surveillance was performed during two seasons (2015–2017) from October 1–April 30 at seven US sites covering an annual catchment population up to 13.7 million adults. Adults (≥ 18 years) admitted to a hospital from the catchment area and with laboratory-confirmed RSV infections identified by clinician-directed testing were included. Demographic data and any history of CHF were abstracted from medical charts. For adults ≥ 65 years, county-level CHF prevalence was obtained from 2015 Centers for Medicare and Medicaid Services (CMS) data. To estimate county-level CHF prevalence for adults < 65 years, we used 2015–2016 National Health and Nutrition Examination Survey and CMS data. We calculated crude incidence rates (and 95% exact Poisson confidence intervals) of RSV by CHF status and age group (< 65 years vs. ≥ 65 years) using RSV cases (numerator) and catchment area county-level population estimates from the US Census (denominator). Results During 2015–2017, a total of 2,211 hospitalized RSV cases were identified; 2,055 (92.9%) had CHF status documented. The majority were ≥ 65 years (n = 1236, 60.1%) and 26.8% (n = 550) had CHF. The crude rate of RSV was 62.7 (95% CI: 57.5–68.2) per 100,000 population in adults with CHF compared with 6.1 (95% CI: 5.7–6.4) per 100,000 population in adults without CHF (rate ratio: 10.3, 95% CI: 9.3–11.3). In both age groups, those with CHF had higher rates of RSV than those without CHF. Rates were highest in adults ≥ 65 years with CHF (73.4 per 100,000 population, 95% CI: 66.4–80.9). Conclusion Using population-based surveillance, we found that adults with CHF had RSV hospitalization rates 10 times higher than those without CHF. Identifying high-risk populations for RSV infection are critical to inform clinical practice and future RSV vaccine policy. Disclosures All authors: No reported disclosures.

scholarly journals Kinetics of Respiratory Syncytial Virus (RSV) Memphis Strain 37 (M37) Infection in the Respiratory Tract of Newborn Lambs as an RSV Infection Model for Human Infants

PLoS ONE ◽  
2015 ◽  
Vol 10 (12) ◽  
pp. e0143580 ◽  
Author(s):  
Alejandro Larios Mora ◽  
Laurent Detalle ◽  
Albert Van Geelen ◽  
Michael S. Davis ◽  
Thomas Stohr ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Infection Model ◽  
Human Infants ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Kinetics Of

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.

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