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Frontiers in Cellular and Infection... 2022Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections and responsible for a large proportion of mortality in children and the... (Review)
Review
Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections and responsible for a large proportion of mortality in children and the elderly. There are no licensed vaccines available to date. Prophylaxis and therapeutic RSV-specific antibodies are limited to populations at high risk owing to high cost and uncertain clinical value. Receptors and host factors are two determinants important for virus entry and establishment of infection . The identification and understanding of viral receptors and host factors can help us to gain insight into the pathogenesis of RSV infection. Herein, we reviewed receptors and host factors that have been reported thus far. RSV could bind to CX3C chemokine receptor 1 and heparan sulfate proteoglycans the G protein, and to nucleolin, insulin-like growth factor-1 receptor, epidermal growth factor, and intercellular adhesion molecule-1 the F protein. Seven host restriction factors and 13 host factors essential for RSV infection were reviewed. We characterized the functions and their roles in the life cycle of RSV, trying to provide an update on the information of RSV-related receptors and host factors.
Topics: Antibodies, Viral; Epidermal Growth Factor; Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 35281439
DOI: 10.3389/fcimb.2022.858629 -
Microbial Genomics Sep 2023Respiratory syncytial virus (RSV), or human orthopneumovirus, is a major cause of acute lower respiratory infection (ALRI), particularly in young children, causing...
Respiratory syncytial virus (RSV), or human orthopneumovirus, is a major cause of acute lower respiratory infection (ALRI), particularly in young children, causing significant morbidity and mortality. We used pathogen genomics to characterize the population structure and genetic signatures of RSV isolates circulating in children in New South Wales between 2016 and 2018 and to understand the evolutionary dynamics of these strains in the context of publicly available RSV genomes from the region and globally. Whole-genome phylogenetic analysis demonstrated the co-circulation of a few major RSV clades in the paediatric population from Sydney. The whole-genome-based genotypes A23 (RSV-A ON1-like genotype) and B6 (RSV-B BA9-like genotype) were the predominant RSV-A and RSV-B genotypes circulating during the study period, respectively. These genotypes were characterized with high levels of diversity of predicted N- and O-linked glycosylation patterns in both the G and F glycoproteins. Interestingly, a novel 72-nucleotide triplication in the sequence that corresponds to the C-terminal region of the gene was identified in four of the A23 genotype sequenced in this study. Consistently, the population dynamics analysis demonstrated a continuous increase in the effective population size of A23 and B6 genotypes globally. Further investigations including functional mapping of mutations and identifying the impact of sequence changes on virus fitness are highly required. This study highlights the potential impact of an integrated approach that uses WG-based phylogeny and studying selective pressure events in understanding the emergence and dissemination of RSV genotypes.
Topics: Child; Humans; Child, Preschool; Phylogeny; Genomics; Respiratory Syncytial Viruses; Genotype; Australia; Respiratory Tract Infections
PubMed: 37656160
DOI: 10.1099/mgen.0.001095 -
The New England Journal of Medicine Feb 2022
Topics: Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 35172061
DOI: 10.1056/NEJMe2118465 -
Nature Sep 2023
Topics: Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 37758879
DOI: 10.1038/d41586-023-02962-2 -
European Journal of Pharmaceutical... Dec 2023Chronic respiratory diseases and infections are among the largest contributors to death globally, many of which still have no cure, including chronic obstructive... (Review)
Review
Chronic respiratory diseases and infections are among the largest contributors to death globally, many of which still have no cure, including chronic obstructive pulmonary disorder, idiopathic pulmonary fibrosis, and respiratory syncytial virus among others. Pulmonary therapeutics afford untapped potential for treating lung infection and disease through direct delivery to the site of action. However, the ability to innovate new therapeutic paradigms for respiratory diseases will rely on modeling the human lung microenvironment and including key cellular interactions that drive disease. One key feature of the lung microenvironment is the air-liquid interface (ALI). ALI interface modeling techniques, using cell-culture inserts, organoids, microfluidics, and precision lung slices (PCLS), are rapidly developing; however, one major component of these models is lacking-innate immune cell populations. Macrophages, neutrophils, and dendritic cells, among others, represent key lung cell populations, acting as the first responders during lung infection or injury. Innate immune cells respond to and modulate stromal cells and bridge the gap between the innate and adaptive immune system, controlling the bodies response to foreign pathogens and debris. In this article, we review the current state of ALI culture systems with a focus on innate immune cells and suggest ways to build on current models to add complexity and relevant immune cell populations.
Topics: Humans; Lung; Pulmonary Disease, Chronic Obstructive; Macrophages; Respiratory Syncytial Virus, Human; Immunity; Immunity, Innate
PubMed: 37770004
DOI: 10.1016/j.ejps.2023.106596 -
Pediatric Allergy and Immunology :... Jun 2022Severe respiratory syncytial virus (RSV) infection in infancy is associated with increased risk of recurrent wheezing in childhood. Both acute and long-term alterations... (Review)
Review
Severe respiratory syncytial virus (RSV) infection in infancy is associated with increased risk of recurrent wheezing in childhood. Both acute and long-term alterations in airway functions are thought to be related to inefficient antiviral immune response. The airway epithelium, the first target of RSV, normally acts as an immunological barrier able to elicit an effective immune reaction but may also be programmed to directly promote a Th2 response, independently from Th2 lymphocyte involvement. Recognition of RSV transcripts and viral replication intermediates by bronchial epithelial cells brings about release of TSLP, IL-33, HMGB1, and IL-25, dubbed "alarmins." These epithelial cell-derived proteins are particularly effective in stimulating innate lymphoid cells 2 (ILC2) to release IL-4, IL-5, and IL-13. ILC2, reflect the innate counterparts of Th2 cells and, when activate, are potent promoters of airway inflammation and hyperresponsiveness in RSV bronchiolitis and childhood wheezing/asthma. Long-term epithelial progenitors or persistent epigenetic modifications of the airway epithelium following RSV infection may play a pathogenetic role in the short- and long-term increased susceptibility to obstructive lung diseases in response to RSV in the young. Additionally, ILC2 function may be further regulated by RSV-induced changes in gut microbiota community composition that can be associated with disease severity in infants. A better understanding of the alarmin-ILC interactions in childhood might provide insights into the mechanisms characterizing these immune-mediated diseases and indicate new targets for prevention and therapeutic interventions.
Topics: Alarmins; Asthma; Bronchiolitis; Humans; Immunity, Innate; Infant; Lymphocytes; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses
PubMed: 35754131
DOI: 10.1111/pai.13803 -
Nature Communications Aug 2021Human respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in young children globally, but little is known about within-host RSV... (Clinical Trial)
Clinical Trial
Human respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in young children globally, but little is known about within-host RSV diversity. Here, we characterised within-host RSV populations using deep-sequencing data from 319 nasopharyngeal swabs collected during 2017-2020. RSV-B had lower consensus diversity than RSV-A at the population level, while exhibiting greater within-host diversity. Two RSV-B consensus sequences had an amino acid alteration (K68N) in the fusion (F) protein, which has been associated with reduced susceptibility to nirsevimab (MEDI8897), a novel RSV monoclonal antibody under development. In addition, several minor variants were identified in the antigenic sites of the F protein, one of which may confer resistance to palivizumab, the only licensed RSV monoclonal antibody. The differences in within-host virus populations emphasise the importance of monitoring for vaccine efficacy and may help to explain the different prevalences of monoclonal antibody-escape mutants between the two subgroups.
Topics: Aged; Antigenic Variation; Female; Genetic Variation; Humans; Infant; Male; Mutation, Missense; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Viral Proteins; Virus Replication
PubMed: 34446722
DOI: 10.1038/s41467-021-25265-4 -
Pneumologie (Stuttgart, Germany) Jun 2020RSV induces an acute viral disease with involvement of the respiratory tract. It can be notably life-threatening for infants but also for older adults. New RSV-subtypes... (Review)
Review
RSV induces an acute viral disease with involvement of the respiratory tract. It can be notably life-threatening for infants but also for older adults. New RSV-subtypes are constantly evolving globally. The knowledge about epidemiology, hygiene measures, diagnostics and clinical feature is essential not only for the paediatrician. Vaccines or specific therapeutics are still missing. This article gives an overview with focus on RSV in adults. In addition, molecular pathological characteristics of the virus are explained, research approaches concerning vaccines and therapeutics are mentioned and current problems in management are discussed.
Topics: Humans; Respiratory Insufficiency; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 32557509
DOI: 10.1055/a-0853-2881 -
The New England Journal of Medicine Apr 2023
Topics: Humans; Infant; Hospitalization; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Aged
PubMed: 37018472
DOI: 10.1056/NEJMe2302646 -
Expert Review of Vaccines Oct 2019: Human respiratory syncytial virus (RSV) is a major health threat both for the very young and the elderly. With yearly 3.2 million hospital admissions and approximately... (Review)
Review
: Human respiratory syncytial virus (RSV) is a major health threat both for the very young and the elderly. With yearly 3.2 million hospital admissions and approximately 118,000 deaths due to RSV in children across the globe, the impact of this infectious disease is very high. Development of a safe RSV vaccine is of utmost importance but has proven to be challenging for several reasons. Researchers are faced with the history of a failed RSV vaccine trial, difficult target populations, a virus that naturally does not induce a long-lasting immune response and ambiguity concerning the optimal correlate of protection. Many different vaccine formats are being tested in preclinical models and about 30 candidate RSV vaccines are being evaluated in clinical trials.: In this review we focus on the difficulties concerning the development of an effective RSV vaccine and discuss vaccines that are currently in clinical trials and how they have dealt with these challenges. We review live-attenuated vaccines, vectored vaccines, subunit vaccines and particle-based vaccines.: It is clear that this field is progressing rapidly with several promising RSV vaccine candidates. A safe and effective RSV vaccine might be on the brink of clinical implementation soon.
Topics: Animals; Clinical Trials as Topic; Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Vaccination; Vaccines, Attenuated; Vaccines, Subunit
PubMed: 31587585
DOI: 10.1080/14760584.2019.1675520