scholarly journals Respiratory syncytial virus infection enhancesPseudomonas aeruginosabiofilm growth through dysregulation of nutritional immunity

2016 ◽  
Vol 113 (6) ◽  
pp. 1642-1647 ◽  
Author(s):  
Matthew R. Hendricks ◽  
Lauren P. Lashua ◽  
Douglas K. Fischer ◽  
Becca A. Flitter ◽  
Katherine M. Eichinger ◽  
...  

Clinical observations link respiratory virus infection andPseudomonas aeruginosacolonization in chronic lung disease, including cystic fibrosis (CF) and chronic obstructive pulmonary disease. The development ofP.aeruginosainto highly antibiotic-resistant biofilm communities promotes airway colonization and accounts for disease progression in patients. Although clinical studies show a strong correlation between CF patients’ acquisition of chronicP.aeruginosainfections and respiratory virus infection, little is known about the mechanism by which chronicP.aeruginosainfections are initiated in the host. Using a coculture model to study the formation of bacterial biofilm formation associated with the airway epithelium, we show that respiratory viral infections and the induction of antiviral interferons promote robust secondaryP.aeruginosabiofilm formation. We report that the induction of antiviral IFN signaling in response to respiratory syncytial virus (RSV) infection induces bacterial biofilm formation through a mechanism of dysregulated iron homeostasis of the airway epithelium. Moreover, increased apical release of the host iron-binding protein transferrin during RSV infection promotesP.aeruginosabiofilm development in vitro and in vivo. Thus, nutritional immunity pathways that are disrupted during respiratory viral infection create an environment that favors secondary bacterial infection and may provide previously unidentified targets to combat bacterial biofilm formation.

1981 ◽  
Vol 86 (3) ◽  
pp. 335-342 ◽  
Author(s):  
D. G. Sims

SUMMARYOver a 24 month period on six paediatric wards of different designs 169 cases of possible hospital-acquired respiratory virus infection were investigated. A variety of viruses was isolated from 82 cases, the most common being respiratory syncytial virus, influenza, parainfluenza, adenoviruses and rhinoviruses. A further 73 children developed respiratory symptoms between 3 and 300 days after admission but viruses were not demonstrable by the techniques used. These children were thought to have hospital-acquired infection nonetheless. Thirteen children were shown not to have acquired infection as the cause of their intercurrent illness. Most acquired infections occurred where toddlers were in cots in open wards. Children with trauma, including non-accidental injury, congenital malformations, mental retardation, failure to thrive or neoplasia were most likely to become infected. Almost 20 % of children suffered from croup or lower respiratory tract illness as a result of their acquired infection. The figure was 41 % if those less than 12 months old were considered alone. Most episodes settled quickly but in a few children investigations or surgery were delayed for a few days.


1970 ◽  
Vol 68 (2) ◽  
pp. 283-292 ◽  
Author(s):  
Joyce McQuillin ◽  
P. S. Gardner ◽  
Patricia M. sturdy

SUMMARYThirty-five consecutive infants admitted into hospital in Newcastle upon Tyne with acute respiratory disease had cough/nasal swabs and nasopharyngeal secretions taken. Both types of specimens were examined the fluorescent antibody technique for respiratory syncytial virus; isolation techniques were also used. Twenty-eight specimens of nasopharyngeal secretion were positive, as were 26 of the corresponding cough/nasal swab preparations. Respiratory syncytial virus was isolated from all but one.Sixteen consecutive children who were only suitable for examination cough/nasal swab preparations were also investigated isolation and fluorescent antibody techniques for respiratory syncytial virus. Respiratory syncytial virus was isolated from eight, seven of whom were positive the fluorescent antibody technique. The use of cough/nasal swab preparations stained the fluorescent antibody technique, although not as efficient as nasopharyngeal secretions, may have a place in the rapid diagnosis of respiratory virus infection in older children and children in general practice. The importance of rapid diagnosis for respiratory virus infection in relationship to antiviral therapy was also discussed.


2020 ◽  
Vol 94 (10) ◽  
Author(s):  
Jian Li ◽  
Miao Li ◽  
Xiuli Wang ◽  
Mengfei Sun ◽  
Cuiqing Ma ◽  
...  

ABSTRACT Respiratory syncytial virus (RSV) is an enveloped RNA virus which is responsible for approximately 80% of lower respiratory tract infections in children. Current lines of evidence have supported the functional involvement of long noncoding RNA (lncRNA) in many viral infectious diseases. However, the overall biological effect and clinical role of lncRNAs in RSV infection remain unclear. In this study, lncRNAs related to respiratory virus infection were obtained from the lncRNA database, and we collected 144 clinical sputum specimens to identify lncRNAs related to RSV infection. Quantitative PCR (qPCR) detection indicated that the expression of lncRNA negative regulator of antiviral response (NRAV) in RSV-positive patients was significantly lower than that in uninfected patients, but lncRNA psoriasis-associated non-protein coding RNA induced by stress (PRINS), nuclear paraspeckle assembly transcript 1 (NEAT1), and Nettoie Salmonella pas Theiler’s (NeST) showed no difference in vivo and in vitro. Meanwhile, overexpression of NRAV promoted RSV proliferation in A549 and BEAS-2B cells, and vice versa, indicating that the downregulation of NRAV was part of the host antiviral defense. RNA fluorescent in situ hybridization (FISH) confirmed that NRAV was mainly located in the cytoplasm. Through RNA sequencing, we found that Rab5c, which is a vesicle transporting protein, showed the same change trend as NRAV. Subsequent investigation revealed that NRAV was able to favor RSV production indirectly by sponging microRNA miR-509-3p so as to release Rab5c and facilitate vesicle transportation. The study provides a new insight into virus-host interaction through noncoding RNA, which may contribute to exploring potential antivirus targets for respiratory virus. IMPORTANCE The mechanism of interaction between RSV and host noncoding RNAs is not fully understood. In this study, we found that the expression of long noncoding RNA (lncRNA) negative regulator of antiviral response (NRAV) was reduced in RSV-infected patients, and overexpression of NRAV facilitated RSV production in vitro, suggesting that the reduction of NRAV in RSV infection was part of the host antiviral response. We also found that NRAV competed with vesicle protein Rab5c for microRNA miR509-3p in cytoplasm to promote RSV vesicle transport and accelerate RSV proliferation, thereby improving our understanding of the pathogenic mechanism of RSV infection.


2013 ◽  
Vol 125 (12) ◽  
pp. 565-574 ◽  
Author(s):  
Hiroki Mori ◽  
Nicole S. Parker ◽  
Deborah Rodrigues ◽  
Kathryn Hulland ◽  
Deborah Chappell ◽  
...  

A significant number of clinical asthma exacerbations are triggered by viral infection. We aimed to characterize the effect of virus infection in an HDM (house dust mite) mouse model of asthma and assess the effect of oral corticosteroids. HDM alone significantly increased eosinophils, lymphocytes, neutrophils, macrophages and a number of cytokines in BAL (bronchoalveolar lavage), all of which were sensitive to treatment with prednisolone (with the exception of neutrophils). Virus infection also induced cell infiltration and cytokines. RSV (respiratory syncytial virus) infection in HDM-treated animals further increased all cell types in BAL (except eosinophils, which declined), but induced no further increase in HDM-elicited cytokines. However, while HDM-elicited TNF-α (tumour necrosis factor-α), IFN-γ (interferon-γ), IL (interleukin)-2, IL-5 and IL-10 were sensitive to prednisolone treatment, concomitant infection with RSV blocked the sensitivity towards steroid. In contrast, influenza infection in HDM- challenged animals resulted in increased BAL lymphocytes, neutrophils, IFN-γ, IL-1β, IL-4, IL-5, IL-10 and IL-12, but all were attenuated by prednisolone treatment. HDM also increased eNO (exhaled NO), which was further increased by concomitant virus infection. This increase was only partially attenuated by prednisolone. RSV infection alone increased BAL mucin. However, BAL mucin was increased in HDM animals with virus infection. Chronic HDM challenge in mice elicits a broad inflammatory response that shares many characteristics with clinical asthma. Concomitant influenza or RSV infection elicits differing inflammatory profiles that differ in their sensitivity towards steroids. This model may be suitable for the assessment of novel pharmacological interventions for asthmatic exacerbation.


2015 ◽  
Vol 2 (1) ◽  
Author(s):  
Terho Heikkinen ◽  
Heikki Valkonen ◽  
Matti Waris ◽  
Olli Ruuskanen

Abstract Background.  Because the production of an effective respiratory syncytial virus (RSV) vaccine for infants is challenging, vaccination of other family members is one viable alternative to prevent severe RSV illnesses in infants. Methods.  In a prospective study, we enrolled all family members of children who were hospitalized with RSV infection. Nasal swabs for RSV detection were obtained from all participating family members. Data on respiratory symptoms in the family members prior to and after the child's admission were collected using standardized questionnaires. Results.  At the time of or within 1 week after the index child's hospitalization, RSV was detected in 40 (77%) of the 52 families and in 60 (47%) of 129 family members. Forty-nine (82%) of RSV detections in the family members were associated with respiratory symptoms. A sibling or a parent was the probable primary case of RSV in 30 (58%) families. Respiratory syncytial virus loads in the nasal swabs were significantly higher (107.7) in index children than in their parents (105.1, P < .0001). Conclusions.  In most cases, the likely source of an infant's RSV infection is an older sibling or a parent. These findings support the strategy of reducing the burden of RSV in infants by vaccination of their family members.


Pathogens ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 106 ◽  
Author(s):  
Glaser ◽  
Coulter ◽  
Shields ◽  
Touzelet ◽  
Power ◽  
...  

The airway epithelium is the primary target of respiratory syncytial virus infection. It is an important component of the antiviral immune response. It contributes to the recruitment and activation of innate immune cells from the periphery through the secretion of cytokines and chemokines. This paper provides a broad review of the cytokines and chemokines secreted from human airway epithelial cell models during respiratory syncytial virus (RSV) infection based on a comprehensive literature review. Epithelium-derived chemokines constitute most inflammatory mediators secreted from the epithelium during RSV infection. This suggests chemo-attraction of peripheral immune cells, such as monocytes, neutrophils, eosinophils, and natural killer cells as a key function of the epithelium. The reports of epithelium-derived cytokines are limited. Recent research has started to identify novel cytokines, the functions of which remain largely unknown in the wider context of the RSV immune response. It is argued that the correct choice of in vitro models used for investigations of epithelial immune functions during RSV infection could facilitate greater progress in this field.


2017 ◽  
Vol 13 (01) ◽  
pp. 046-050 ◽  
Author(s):  
Jacob Simonsen ◽  
Morten Breindahl ◽  
Louise Winding ◽  
Poul-Erik Kofoed ◽  
Lone Stensballe

Introduction Prior studies found associations between respiratory syncytial virus (RSV) infection, wheezing, and asthma. The present study aimed to examine the risk of wheezing after RSV, by the history of wheezing. Methods We included 39 children hospitalized for RSV infection (cases) and 23 children hospitalized for nonrespiratory tract infection reasons (controls) and followed the children prospectively with regular standardized telephone interviews until 18 months, and again 5 years after inclusion. The risk of wheeze was estimated by odds ratios (OR), comparing children hospitalized for RSV with children hospitalized for other reasons and stratified by wheezing history. Results Eighteen months after hospitalization for RSV, the adjusted OR of wheezing was 3.16 (95% confidence interval: 0.75–13.3). The effect of hospitalization for RSV on the risk of wheeze was significantly present among children who did not wheeze already before inclusion (adjusted OR: 11.83; 95% confidence interval: 1.12–124.9), while the adjusted OR of wheeze was 0.95 (95% confidence interval: 0.10–9.00) among children who wheezed already before inclusion. The adjusted OR of wheeze after hospitalization for RSV among children who did not wheeze before inclusion was 8.50 (95% confidence interval: 0.79–91.6) 5 years after inclusion. Conclusion We conclude that the effect of severe RSV infection requiring hospitalization differs according to the history of wheezing, and wanes with time. We recommend that future studies on severe RSV infection and the risk of subsequent wheeze and asthma include information on prior wheeze and asthma.


2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S318-S319
Author(s):  
Hung Fu Tseng ◽  
Lina S Sy ◽  
Bradley Ackerson ◽  
Christine Fischetti ◽  
Jeff Slezak ◽  
...  

Abstract Background There is increasing evidence that respiratory syncytial virus (RSV) infection can cause serious health problems among older adults, whether healthy and community-dwelling, or high-risk. In older adults, RSV infection can lead to complications that are similar to those resulting from seasonal influenza infection. The aim of this study was to compare the morbidity and mortality in older adults ≥60 years hospitalized with RSV disease vs. those hospitalized with seasonal influenza. Methods This cohort study included members of Kaiser Permanente Southern California aged ≥ 60 years who tested positive for RSV or influenza A/B by multiplex RT-PCR in clinical diagnostic testing during January 1, 2011 to June 30, 2015 and were hospitalized. For multiple eligible hospitalizations, only the first RSV hospitalization for the RSV cohort or first influenza A/B hospitalization for the influenza cohort was included. Electronic medical records for each hospitalized individual were used to extract necessary information, including baseline characteristics, symptoms, comorbidities, and outcomes. Results The study included 664 RSV (mean age 78.5 years, 39.5% male) and 1922 influenza A/B (mean age 77.5 years, 49.7% male) hospitalizations. There were 310 (46.7%) RSV patients and 501 (26.1%) influenza patients with a diagnosis of pneumonia. There were 119 RSV patients (17.9%) vs. 272 (14.2%) influenza patients that were admitted to the intensive care unit during hospitalization (mean stay 6.8 vs. 7.8 days). The short-term mortality rate during hospitalization and within 90 days of discharge was 5.6% (n = 37) and 7.4% (n = 49) in the RSV cohort vs. 4.4% (n = 85) and 6.7%
(n = 129) in the influenza cohort. The intermediate-term mortality rate within 91–180 days of discharge was significantly different between the RSV and the influenza cohorts (4.4% vs. 2.5%). Conclusion RSV infection can lead to complications and severe outcomes that are similar to those of seasonal influenza in older adults. Effective prevention and treatment strategies such as vaccination and antivirals against RSV could potentially reduce the burden of RSV infection as well as complications from disease. Disclosures H. F. Tseng, Novavax: Grant Investigator, Research grant. L. S. Sy, Novavax: Collaborator, Research grant. C. Fischetti, Novavax: Collaborator, Research grant. J. Slezak, Novavax: Collaborator, Grant recipient. Y. Luo, Novavax: Collaborator, Grant recipient. Z. Solano, Novavax Inc.: Collaborator, My employer received research funds to conduct the study. S. Chen, Novavax: Collaborator, Research grant. V. Shinde, Novavax Inc.: Collaborator, My employer received research funds to conduct the study.


PEDIATRICS ◽  
1990 ◽  
Vol 86 (6) ◽  
pp. 848-855
Author(s):  
Mikko Arola ◽  
Olli Ruuskanen ◽  
Thedi Ziegler ◽  
Jussi Mertsola ◽  
Kirsti Näntö-Salonen ◽  
...  

The clinical characteristics of acute otitis media in relation to coexisting respiratory virus infection were studied in a 1-year prospective study of 363 children with acute otitis media. Respiratory viruses were detected using virus isolation and virus antigen detection in nasopharyngeal specimens of 42% of the patients at the time of diagnosis. Rhinovirus (24%) and respiratory syncytical virus (13%) were the two most common viruses detected. Adenovirus, parainfluenza viruses, and coronavirus OC43 were found less frequently. The mean duration of preceding symptoms was 5.9 days before the diagnosis of acute otitis media. Ninety-four percent of the children had symptoms of upper respiratory tract infection. Fever was reported in 55% and earache in 47% of cases. Patients with respiratory syncytial virus infection had fever, cough, and vomiting significantly more often than patients with rhinovirus infection or virus-negative patients. No significant differences were found in the appearance of the tympanic membrane and outcome of illness between virus-negative and virus-positive patients with acute otitis. Most patients respond well to antimicrobial therapy despite the coexisting viral infection. If the symptoms of infection persist, they can be due to the underlying viral infection, and viral diagnostics preferably with rapid methods may be clinically useful in these patients.


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