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Frontiers in Immunology 2022Respiratory tract infections are a leading cause of morbidity and mortality in newborns, infants, and young children. These early life infections present a formidable... (Review)
Review
Respiratory tract infections are a leading cause of morbidity and mortality in newborns, infants, and young children. These early life infections present a formidable immunologic challenge with a number of possibly conflicting goals: simultaneously eliminate the acute pathogen, preserve the primary gas-exchange function of the lung parenchyma in a developing lung, and limit long-term sequelae of both the infection and the inflammatory response. The latter has been most well studied in the context of childhood asthma, where multiple epidemiologic studies have linked early life viral infection with subsequent bronchospasm. This review will focus on the clinical relevance of respiratory syncytial virus (RSV), human metapneumovirus (HMPV), and rhinovirus (RV) and examine the protective and pathogenic host responses within the neonate.
Topics: Child; Child, Preschool; Humans; Immunity; Infant; Infant, Newborn; Metapneumovirus; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Viruses
PubMed: 35493465
DOI: 10.3389/fimmu.2022.863149 -
Nature Reviews. Microbiology Feb 2023This study reports that SARS-CoV-2 binds to cilia and reprogrammes microvilli to promote replication in the nasal airway.
This study reports that SARS-CoV-2 binds to cilia and reprogrammes microvilli to promote replication in the nasal airway.
Topics: Mucus; SARS-CoV-2; Cilia; Respiratory Syncytial Virus, Human
PubMed: 36513767
DOI: 10.1038/s41579-022-00842-6 -
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 -
Archivos de Bronconeumologia Apr 2022
Topics: Humans; Infant; Respiratory Syncytial Virus, Human
PubMed: 34226785
DOI: 10.1016/j.arbres.2021.06.007 -
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 -
The Journal of Infectious Diseases Jan 2019
Topics: Bronchiolitis; Genotype; Humans; Infant; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses
PubMed: 30215722
DOI: 10.1093/infdis/jiy498 -
The Journal of Infectious Diseases May 2018
Topics: Genotype; Mexico; Respiratory Syncytial Virus, Human
PubMed: 29562333
DOI: 10.1093/infdis/jiy155