scholarly journals Early-Life Respiratory Syncytial Virus Infection, Trained Immunity and Subsequent Pulmonary Diseases

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 505 ◽  
Author(s):  
Carrie-Anne Malinczak ◽  
Nicholas W. Lukacs ◽  
Wendy Fonseca
Keyword(s):  
Immune System ◽  
Respiratory Syncytial Virus ◽  
Viral Infection ◽  
Childhood Asthma ◽  
Early Life ◽  
Pulmonary Diseases ◽  
Respiratory Viral Infection ◽  
Rsv Infection ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) is often the first clinically relevant pathogen encountered in life, with nearly all children infected by two years of age. Many studies have also linked early-life severe respiratory viral infection with more pathogenic immune responses later in life that lead to pulmonary diseases like childhood asthma. This phenomenon is thought to occur through long-term immune system alterations following early-life respiratory viral infection and may include local responses such as unresolved inflammation and/or direct structural or developmental modifications within the lung. Furthermore, systemic responses that could impact the bone marrow progenitors may be a significant cause of long-term alterations, through inflammatory mediators and shifts in metabolic profiles. Among these alterations may be changes in transcriptional and epigenetic programs that drive persistent modifications throughout life, leaving the immune system poised toward pathogenic responses upon secondary insult. This review will focus on early-life severe RSV infection and long-term alterations. Understanding these mechanisms will not only lead to better treatment options to limit initial RSV infection severity but also protect against the development of childhood asthma linked to severe respiratory viral infections.

scholarly journals Infantile respiratory syncytial virus and human rhinovirus infections: respective role in inception and persistence of wheezing

2014 ◽  
Vol 45 (3) ◽  
pp. 774-789 ◽  
Author(s):  
Giovanni A. Rossi ◽  
Andrew A. Colin
Keyword(s):  
Respiratory Syncytial Virus ◽  
Airway Disease ◽  
Epidemiological Studies ◽  
Human Rhinovirus ◽  
Allergic Sensitisation ◽  
Cytokines And Chemokines ◽  
Rsv Infection ◽  
History Of ◽  
Syncytial Virus

There is evidence that respiratory viruses play a key role in the development and exacerbation of obstructive respiratory diseases in children. This review attempts to juxtapose the separate profiles and prototypes of pathogenenetic mechanisms represented by the two most common amongst such viruses: respiratory syncytial virus (RSV) and human rhinovirus (HRV).RSV represents the most common agent of severe airway disease in infants and young children, and is predominant in winter months. Large epidemiological studies have revealed an unequivocal relationship between RSV infection and subsequent wheezing into childhood, thought to be related to long-term changes in neuroimmune control of the airways rather than allergic sensitisation.HRV is a highly diverse group of viruses that affect subjects of all ages, is ubiquitous and occurs year-round. In contrast to RSV, infections with HRV cause minimal cytotoxicity but induce a rapid production of cytokines and chemokines with amplification of the inflammatory response. The susceptibility to HRV-induced bronchiolitis and subsequent wheezing appears to be linked to individual predisposition since it is often associated with a family or personal history of asthma/atopy.Thus, RSV probably serves as an “inducer” rather than a “trigger”. Conversely, HRVs seem to serve as a “trigger” rather than an “inducer” in predisposed individuals.

scholarly journals Metabolic Reprogramming of Nasal Airway Epithelial Cells Following Infant Respiratory Syncytial Virus Infection

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2055
Author(s):  
Andrew R. Connelly ◽  
Brian M. Jeong ◽  
Mackenzie E. Coden ◽  
Jacob Y. Cao ◽  
Tatiana Chirkova ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Epithelial Cells ◽  
Early Life ◽  
Airway Epithelial Cells ◽  
Metabolic Reprogramming ◽  
Flux Analysis ◽  
Nasal Airway ◽  
Airway Epithelial ◽  
Rsv Infection ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) is a seasonal mucosal pathogen that infects the ciliated respiratory epithelium and results in the most severe morbidity in the first six months of life. RSV is a common cause of acute respiratory infection during infancy and is an important early-life risk factor strongly associated with asthma development. While this association has been repeatedly demonstrated, limited progress has been made on the mechanistic understanding in humans of the contribution of infant RSV infection to airway epithelial dysfunction. An active infection of epithelial cells with RSV in vitro results in heightened central metabolism and overall hypermetabolic state; however, little is known about whether natural infection with RSV in vivo results in lasting metabolic reprogramming of the airway epithelium in infancy. To address this gap, we performed functional metabolomics, 13C glucose metabolic flux analysis, and RNA-seq gene expression analysis of nasal airway epithelial cells (NAECs) sampled from infants between 2–3 years of age, with RSV infection or not during the first year of life. We found that RSV infection in infancy was associated with lasting epithelial metabolic reprogramming, which was characterized by (1) significant increase in glucose uptake and differential utilization of glucose by epithelium; (2) altered preferences for metabolism of several carbon and energy sources; and (3) significant sexual dimorphism in metabolic parameters, with RSV-induced metabolic changes most pronounced in male epithelium. In summary, our study supports the proposed phenomenon of metabolic reprogramming of epithelial cells associated with RSV infection in infancy and opens exciting new venues for pursuing mechanisms of RSV-induced epithelial barrier dysfunction in early life.

scholarly journals Macrolide Therapy in Respiratory Viral Infections

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Jin-Young Min ◽  
Yong Ju Jang
Keyword(s):  
Influenza Virus ◽  
Viral Infection ◽  
Viral Infections ◽  
Wide Spectrum ◽  
Influenza Virus Infection ◽  
Respiratory Viral Infection ◽  
Rsv Infection ◽  
Respiratory Viral Infections ◽  
Syncytial Virus ◽  
Viral Titers

Background. Macrolides have received considerable attention for their anti-inflammatory and immunomodulatory actions beyond the antibacterial effect. These two properties may ensure some efficacy in a wide spectrum of respiratory viral infections. We aimed to summarize the properties of macrolides and their efficacy in a range of respiratory viral infection.Methods. A search of electronic journal articles through PubMed was performed using combinations of the following keywords including macrolides and respiratory viral infection.Results. Bothin vitroandin vivostudies have provided evidence of their efficacy in respiratory viral infections including rhinovirus (RV), respiratory syncytial virus (RSV), and influenza virus. Much data showed that macrolides reduced viral titers of RV ICAM-1, which is the receptor for RV, and RV infection-induced cytokines including IL-1β, IL-6, IL-8, and TNF-α. Macrolides also reduced the release of proinflammatory cytokines which were induced by RSV infection, viral titers, RNA of RSV replication, and the susceptibility to RSV infection partly through the reduced expression of activated RhoA which is an RSV receptor. Similar effects of macrolides on the influenza virus infection and augmentation of the IL-12 by macrolides which is essential in reducing virus yield were revealed.Conclusion. This paper provides an overview on the properties of macrolides and their efficacy in various respiratory diseases.

scholarly journals The specific features of the developing T cell compartment of the neonatal lung are a determinant of respiratory syncytial virus immunopathogenesis

2021 ◽  
Vol 17 (4) ◽  
pp. e1009529
Author(s):  
Thomas Démoulins ◽  
Melanie Brügger ◽  
Beatrice Zumkehr ◽  
Blandina I. Oliveira Esteves ◽  
Kemal Mehinagic ◽  
...  
Keyword(s):  
T Cells ◽  
Respiratory Syncytial Virus ◽  
T Cell ◽  
Disease Severity ◽  
Early Life ◽  
Cell Compartment ◽  
Neonatal Lung ◽  
Rsv Infection ◽  
Syncytial Virus

The human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants, possibly due to the properties of the immature neonatal pulmonary immune system. Using the newborn lamb, a classical model of human lung development and a translational model of RSV infection, we aimed to explore the role of cell-mediated immunity in RSV disease during early life. Remarkably, in healthy conditions, the developing T cell compartment of the neonatal lung showed major differences to that seen in the mature adult lung. The most striking observation being a high baseline frequency of bronchoalveolar IL-4-producing CD4 and CD8 T cells, which declined progressively over developmental age. RSV infection exacerbated this pro-type 2 environment in the bronchoalveolar space, rather than inducing a type 2 response per se. Moreover, regulatory T cell suppressive functions occurred very early to dampen this pro-type 2 environment, rather than shutting them down afterwards, while γδ T cells dropped and failed to produce IL-17. Importantly, RSV disease severity was related to the magnitude of those unconventional bronchoalveolar T cell responses. These findings provide novel insights in the mechanisms of RSV immunopathogenesis in early life, and constitute a major step for the understanding of RSV disease severity.

scholarly journals Epidemiologic, Experimental, and Clinical Links between Respiratory Syncytial Virus Infection and Asthma

2008 ◽  
Vol 21 (3) ◽  
pp. 495-504 ◽  
Author(s):  
Shyam S. Mohapatra ◽  
Sandhya Boyapalle
Keyword(s):  
Respiratory Syncytial Virus ◽  
Childhood Asthma ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Severe Disease ◽  
Infection Process ◽  
Increased Risk ◽  
Rsv Infection ◽  
Recurrent Wheeze ◽  
Syncytial Virus

SUMMARY Virtually all children experience respiratory syncytial virus (RSV) infection at least once during the first 2 years of life, but only a few develop bronchiolitis and more severe disease requiring hospitalization, usually in the first 6 months of life. Children who recover from RSV-induced bronchiolitis are at increased risk for the development of recurrent wheeze and asthma in later childhood. Recent studies suggest that there is an association between RSV-induced bronchiolitis and asthma within the first decade of life but that this association is not significant after age 13. Despite the considerable progress made in our understanding of several aspects of respiratory viral infections, further work needs to be done to clarify the molecular mechanisms of early interactions between virus and host cell and the role of host gene products in the infection process. This review provides a critical appraisal of the literature in epidemiology and experimental research which links RSV infection to asthma. Studies to date demonstrate that there is a significant association between RSV infection and childhood asthma and that preventing severe primary RSV infections can decrease the risk of childhood asthma.

scholarly journals A Durable Relationship: Respiratory Syncytial Virus Bronchiolitis and Asthma past Their Golden Anniversary

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 201 ◽  
Author(s):  
Ignacio Esteban ◽  
Renato T. Stein ◽  
Fernando P. Polack
Keyword(s):  
Respiratory Syncytial Virus ◽  
Acute Illness ◽  
Preventive Strategies ◽  
Biological Mechanisms ◽  
Recurrent Wheezing ◽  
Impaired Lung Function ◽  
Viral Illness ◽  
Rsv Infection ◽  
Syncytial Virus

Numerous preventive strategies against respiratory syncytial virus (RSV) are undergoing late stage evaluation in humans and, in addition to their intended benefit for acute illness, may impact long term consequences of infection in infants. Severe RSV infection has been repeatedly associated in the literature with long term complications, including impaired lung function, recurrent wheezing, and asthma. However, whether RSV lower respiratory tract infection (LRTI) causally affects the odds for developing wheezing and/or asthma during childhood requires further study, and the biological mechanisms underlying this hypothetical progression from viral illness to chronic lung disease are poorly characterized. In this review, we summarize the literature exploring the association between RSV LRTI in infancy and subsequent recurrent wheezing and pediatric asthma.

scholarly journals Anti-Respiratory Syncytial Virus (RSV) Neutralizing Antibody Decreases Lung Inflammation, Airway Obstruction, and Airway Hyperresponsiveness in a Murine RSV Model

2004 ◽  
Vol 48 (5) ◽  
pp. 1811-1822 ◽  
Author(s):  
Asunción Mejías ◽  
Susana Chávez-Bueno ◽  
Ana María Ríos ◽  
Jesús Saavedra-Lozano ◽  
Mónica Fonseca Aten ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Airway Obstruction ◽  
Airway Hyperresponsiveness ◽  
Strong Association ◽  
Neutralizing Antibody ◽  
Clinical Markers ◽  
Recurrent Wheezing ◽  
Rsv Infection ◽  
Syncytial Virus

ABSTRACT Numerous studies have described a strong association between respiratory syncytial virus (RSV) infection in infancy and the development of recurrent wheezing and airway hyperresponsiveness. We evaluated the effect of an anti-RSV neutralizing monoclonal antibody (palivizumab) on different aspects of RSV disease by using a murine model. BALB/c mice were intranasally inoculated with RSV A2. Palivizumab or an isotype-matched control antibody was administered once at 24 h before inoculation, 1 h after inoculation, or 48 h after inoculation. Regardless of the timing of administration, all mice treated with the neutralizing antibody showed significantly decreased RSV loads in bronchoalveolar lavage (BAL) and lung specimens compared with those of infected controls. Pulmonary histopathologic scores, airway obstruction measured by plethysmography, and airway hyperresponsiveness after methacholine challenge were significantly reduced in mice treated with the anti-RSV antibody 24 h before inoculation compared with those for untreated controls. Concentrations of interferon-gamma, interleukin-10, macrophage inflammatory protein 1α, regulated on activation normal T-cell expressed and secreted (RANTES), and eotaxin in BAL fluids were also significantly reduced in mice treated with palivizumab 24 h before inoculation. This study demonstrates that reduced RSV replication was associated with significant modulation of inflammatory and clinical markers of acute disease severity and significant improvement of the long-term pulmonary abnormalities. Studies to determine whether strategies aimed at preventing or reducing RSV replication could decrease the long-term morbidity associated with RSV infection in children should be considered.

scholarly journals Respiratory Viral Infections in Infants: Causes, Clinical Symptoms, Virology, and Immunology

2010 ◽  
Vol 23 (1) ◽  
pp. 74-98 ◽  
Author(s):  
John S. Tregoning ◽  
Jürgen Schwarze
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Viral Infection ◽  
Viral Infections ◽  
Clinical Symptoms ◽  
Later Life ◽  
Treatment Needs ◽  
Syncytial Virus ◽  
Degree Of Similarity

SUMMARY In global terms, respiratory viral infection is a major cause of morbidity and mortality. Infancy, in particular, is a time of increased disease susceptibility and severity. Early-life viral infection causes acute illness and can be associated with the development of wheezing and asthma in later life. The most commonly detected viruses are respiratory syncytial virus (RSV), rhinovirus (RV), and influenza virus. In this review we explore the complete picture from epidemiology and virology to clinical impact and immunology. Three striking aspects emerge. The first is the degree of similarity: although the infecting viruses are all different, the clinical outcome, viral evasion strategies, immune response, and long-term sequelae share many common features. The second is the interplay between the infant immune system and viral infection: the immaturity of the infant immune system alters the outcome of viral infection, but at the same time, viral infection shapes the development of the infant immune system and its future responses. Finally, both the virus and the immune response contribute to damage to the lungs and subsequent disease, and therefore, any prevention or treatment needs to address both of these factors.

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.

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