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Medical Science Monitor : International... Dec 2023In October and November 2023, hospitals in the major cities of Beijing and Liaoning in northern China reported a surge in cases of pneumonia in children, with some...
In October and November 2023, hospitals in the major cities of Beijing and Liaoning in northern China reported a surge in cases of pneumonia in children, with some hospitals being overwhelmed by pediatric emergency admissions. Similar outbreaks of childhood pneumonia had been reported in the autumn of 2022 in Europe and North America. Therefore, increased reports of childhood pneumonia could be driven by post-pandemic changes in the pathogenesis of endemic respiratory infections other than COVID-19, including Mycoplasma pneumoniae, respiratory syncytial virus (RSV), and influenza, rather than emerging novel pathogens. However, the recent reports of increased hospitalizations for children with pneumonia warrant continued infection surveillance and monitoring to exclude new respiratory pathogens or more virulent variants of known pathogens, including SARS-CoV-2. This editorial aims to present what is known about the re-emergence of endemic respiratory infections, which may be the cause of the recently reported outbreaks of childhood pneumonia.
Topics: Humans; Child; Pandemics; Respiratory Tract Infections; Pneumonia; Respiratory Syncytial Virus, Human; Influenza, Human
PubMed: 38037346
DOI: 10.12659/MSM.943312 -
Frontiers in Immunology 2019The pneumoviruses respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two widespread human pathogens that can cause severe disease in the young, the... (Review)
Review
The pneumoviruses respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two widespread human pathogens that can cause severe disease in the young, the elderly, and the immunocompromised. Despite the discovery of RSV over 60 years ago, and hMPV nearly 20 years ago, there are no approved vaccines for either virus. Antibody-mediated immunity is critical for protection from RSV and hMPV, and, until recently, knowledge of the antibody epitopes on the surface glycoproteins of RSV and hMPV was very limited. However, recent breakthroughs in the recombinant expression and stabilization of pneumovirus fusion proteins have facilitated in-depth characterization of antibody responses and structural epitopes, and have provided an enormous diversity of new monoclonal antibody candidates for therapeutic development. These new data have primarily focused on the RSV F protein, and have led to a wealth of new vaccine candidates in preclinical and clinical trials. In contrast, the major structural antibody epitopes remain unclear for the hMPV F protein. Overall, this review will cover recent advances in characterizing the antigenic sites on the RSV and hMPV F proteins.
Topics: Antibodies, Monoclonal; Antibodies, Viral; Antigens, Viral; Cost of Illness; Epitopes; Global Health; Humans; Pneumovirus; Pneumovirus Infections; Protein Binding; Public Health Surveillance; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Structure-Activity Relationship; Viral Fusion Proteins
PubMed: 31849961
DOI: 10.3389/fimmu.2019.02778 -
Revue Medicale Suisse Feb 2024
Topics: Humans; Respiratory Syncytial Viruses; mRNA Vaccines
PubMed: 38323773
DOI: 10.53738/REVMED.2024.20.860.326 -
Proceedings of the National Academy of... Jan 2023The resolution of infection is an active process with specific molecular and cellular mechanisms that temper inflammation and enhance pathogen clearance. Here, the...
The resolution of infection is an active process with specific molecular and cellular mechanisms that temper inflammation and enhance pathogen clearance. Here, the specialized pro-resolving mediator (SPM) Maresin 1 (MaR1) inhibited respiratory syncytial virus (RSV)-induced inflammation. inlerleukin-13 production from type 2 innate lymphoid cells (ILC) and CD4 T helper type 2 cells was decreased by exogenous MaR1. In addition, MaR1 increased amphiregulin production and decreased RSV viral transcripts to promote resolution. MaR1 also promoted interferon-β production in mouse lung tissues and also in pediatric lung slices. MaR1 significantly inhibited the RSV-triggered aberrant inflammatory phenotype in FoxP3-expressing Tregs. The receptor for MaR1, leucine-rich repeat-containing G protein-coupled receptor 6 (LGR6), was constitutively expressed on Tregs. Following RSV infection, mice lacking Lgr6 had exacerbated type 2 immune responses with an increased viral burden and blunted responses to MaR1. Together, these findings have uncovered a multi-pronged protective signaling axis for MaR1-Lgr6, improving Tregs's suppressive function and upregulating host antiviral genes resulting in decreased viral burden and pathogen-mediated inflammation, ultimately promoting restoration of airway mucosal homeostasis.
Topics: Mice; Animals; Immunity, Innate; Lymphocytes; Inflammation; Respiratory Syncytial Virus Infections; Docosahexaenoic Acids; Pneumonia, Viral; Respiratory Syncytial Virus, Human; Receptors, G-Protein-Coupled
PubMed: 36595677
DOI: 10.1073/pnas.2206480120 -
Archivos de Bronconeumologia Apr 2022
Topics: Humans; Infant; Respiratory Syncytial Virus, Human
PubMed: 34226785
DOI: 10.1016/j.arbres.2021.06.007 -
Frontiers in Immunology 2023Respiratory syncytial virus (RSV) and Rhinovirus (RV) infections are major triggers of severe lower respiratory illnesses (sLRI) in infants and children and are strongly...
Respiratory syncytial virus (RSV) and Rhinovirus (RV) infections are major triggers of severe lower respiratory illnesses (sLRI) in infants and children and are strongly associated with the subsequent development of asthma. Decades of research has focused on the role of type I interferons in antiviral immunity and ensuing airway diseases, however, recent findings have highlighted several novel aspects of the interferon response that merit further investigation. In this perspective, we discuss emerging roles of type I interferons in the pathogenesis of sLRI in children. We propose that variations in interferon response patterns exist as discrete endotypes, which operate locally in the airways and systemically through a lung-blood-bone marrow axis. We discuss new insights into the role of interferons in immune training, bacterial lysate immunotherapy, and allergen-specific immunotherapy. Interferons play complex and diverse roles in the pathogenesis of sLRI and later asthma, providing new directions for mechanistic studies and drug development.
Topics: Infant; Child; Humans; Asthma; Antiviral Agents; Respiratory Syncytial Virus, Human; Interferon Type I; Virus Diseases
PubMed: 36895568
DOI: 10.3389/fimmu.2023.1109001 -
Nature Jul 2021Biomolecular condensates have emerged as an important subcellular organizing principle. Replication of many viruses, including human respiratory syncytial virus (RSV),...
Biomolecular condensates have emerged as an important subcellular organizing principle. Replication of many viruses, including human respiratory syncytial virus (RSV), occurs in virus-induced compartments called inclusion bodies (IBs) or viroplasm. IBs of negative-strand RNA viruses were recently shown to be biomolecular condensates that form through phase separation. Here we report that the steroidal alkaloid cyclopamine and its chemical analogue A3E inhibit RSV replication by disorganizing and hardening IB condensates. The actions of cyclopamine and A3E were blocked by a point mutation in the RSV transcription factor M2-1. IB disorganization occurred within minutes, which suggests that these molecules directly act on the liquid properties of the IBs. A3E and cyclopamine inhibit RSV in the lungs of infected mice and are condensate-targeting drug-like small molecules that have in vivo activity. Our data show that condensate-hardening drugs may enable the pharmacological modulation of not only many previously undruggable targets in viral replication but also transcription factors at cancer-driving super-enhancers.
Topics: Animals; Antiviral Agents; Biomolecular Condensates; Cell Line; Female; Humans; Inclusion Bodies; Lung; Mice; Mice, Inbred BALB C; Respiratory Syncytial Virus, Human; Transcription Factors; Veratrum Alkaloids; Viral Proteins; Virus Replication
PubMed: 34234347
DOI: 10.1038/s41586-021-03703-z -
The New England Journal of Medicine Jul 2020
Topics: Female; Humans; Infant; Pregnancy; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Vaccination
PubMed: 32726536
DOI: 10.1056/NEJMe2021648 -
Pediatric Critical Care Medicine : a... Aug 2019
Topics: Anti-Bacterial Agents; Child; Child, Preschool; Humans; Respiratory Insufficiency; Respiratory Syncytial Viruses
PubMed: 31397821
DOI: 10.1097/PCC.0000000000002030 -
Cells Mar 2022Despite over half a century of research, respiratory syncytial virus (RSV)-induced bronchiolitis remains a major cause of hospitalisation in infancy, while vaccines and... (Review)
Review
Despite over half a century of research, respiratory syncytial virus (RSV)-induced bronchiolitis remains a major cause of hospitalisation in infancy, while vaccines and specific therapies still await development. Our understanding of mucosal immune responses to RSV continues to evolve, but recent studies again highlight the role of Type-2 immune responses in RSV disease and hint at the possibility that it dampens Type-1 antiviral immunity. Other immunoregulatory pathways implicated in RSV disease highlight the importance of focussing on localised mucosal responses in the respiratory mucosa, as befits a virus that is essentially confined to the ciliated respiratory epithelium. In this review, we discuss studies of mucosal immune cell infiltration and production of inflammatory mediators in RSV bronchiolitis and relate these studies to observations from peripheral blood. We also discuss the advantages and limitations of studying the nasal mucosa in a disease that is most severe in the lower airway. A fresh focus on studies of RSV pathogenesis in the airway mucosa is set to revolutionise our understanding of this common and important infection.
Topics: Bronchiolitis; Humans; Immunity, Mucosal; Nasal Mucosa; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 35406717
DOI: 10.3390/cells11071153