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The Lancet. Respiratory Medicine Oct 2021
Topics: Child, Preschool; Combined Modality Therapy; Humans; Infant; Internationality; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; United Kingdom
PubMed: 34597586
DOI: 10.1016/S2213-2600(21)00411-2 -
Viral Immunology Mar 2018Human parainfluenza viruses (family Paramyxoviridae), human metapneumovirus, and respiratory syncytial virus (family Pneumoviridae) infect most infants and children... (Review)
Review
Human parainfluenza viruses (family Paramyxoviridae), human metapneumovirus, and respiratory syncytial virus (family Pneumoviridae) infect most infants and children within the first few years of life and are the etiologic agents for many serious acute respiratory illnesses. These virus infections are also associated with long-term diseases that impact quality of life, including asthma. Despite over a half-century of vaccine research, development, and clinical trials, no vaccine has been licensed to date for the paramyxoviruses or pneumoviruses for the youngest infants. In this study, we describe the recent reclassification of paramyxoviruses and pneumoviruses into distinct families by the International Committee on the Taxonomy of Viruses. We also discuss some past unsuccessful vaccine trials and some currently preferred vaccine strategies. Finally, we discuss hurdles that must be overcome to support successful respiratory virus vaccine development for the youngest children.
Topics: Animals; Clinical Trials as Topic; Drug Discovery; Drug Evaluation, Preclinical; Humans; Paramyxoviridae Infections; Paramyxovirinae; Pneumovirinae; Respiratory Syncytial Virus Infections; Viral Vaccines
PubMed: 29323621
DOI: 10.1089/vim.2017.0137 -
Signal Transduction and Targeted Therapy Aug 2023Respiratory syncytial virus (RSV) is a nonsegmented, negative strand RNA virus that has caused severe lower respiratory tract infections of high mortality rates in...
Respiratory syncytial virus (RSV) is a nonsegmented, negative strand RNA virus that has caused severe lower respiratory tract infections of high mortality rates in infants and the elderly, yet no effective vaccine or antiviral therapy is available. The RSV genome encodes the nucleoprotein (N) that forms helical assembly to encapsulate and protect the RNA genome from degradation, and to serve as a template for transcription and replication. Previous crystal structure revealed a decameric ring architecture of N in complex with the cellular RNA (N-RNA) of 70 nucleotides (70-nt), whereas cryo-ET reconstruction revealed a low-resolution left-handed filament, in which the crystal monomer structure was docked with the helical symmetry applied to simulate a nucleocapsid-like assembly of RSV. However, the molecular details of RSV nucleocapsid assembly remain unknown, which continue to limit our complete understanding of the critical interactions involved in the nucleocapsid and antiviral development that may target this essential process during the viral life cycle. Here we resolve the near-atomic cryo-EM structure of RSV N-RNA that represents roughly one turn of the helical assembly that unveils critical interaction interfaces of RSV nucleocapsid and may facilitate development of RSV antiviral therapy.
Topics: Aged; Infant; Humans; Respiratory Syncytial Viruses; Cryoelectron Microscopy; Nucleocapsid; Antiviral Agents; RNA
PubMed: 37607909
DOI: 10.1038/s41392-023-01602-5 -
Viruses May 2021RNA synthesis in respiratory syncytial virus (RSV), a negative-sense (-) nonsegmented RNA virus, consists of viral gene transcription and genome replication. Gene... (Review)
Review
RNA synthesis in respiratory syncytial virus (RSV), a negative-sense (-) nonsegmented RNA virus, consists of viral gene transcription and genome replication. Gene transcription includes the positive-sense (+) viral mRNA synthesis, 5'-RNA capping and methylation, and 3' end polyadenylation. Genome replication includes (+) RNA antigenome and (-) RNA genome synthesis. RSV executes the viral RNA synthesis using an RNA synthesis ribonucleoprotein (RNP) complex, comprising four proteins, the nucleoprotein (N), the large protein (L), the phosphoprotein (P), and the M2-1 protein. We provide an overview of the RSV RNA synthesis and the structural insights into the RSV gene transcription and genome replication process. We propose a model of how the essential four proteins coordinate their activities in different RNA synthesis processes.
Topics: Animals; Genome, Viral; Humans; RNA, Viral; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Ribonucleoproteins; Viral Proteins
PubMed: 34063087
DOI: 10.3390/v13050834 -
Epidemiology and Infection May 2023This study aims to evaluate the impact of non-pharmaceutical interventions (NPIs) on the prevalence of respiratory pathogens among hospitalised children with acute...
This study aims to evaluate the impact of non-pharmaceutical interventions (NPIs) on the prevalence of respiratory pathogens among hospitalised children with acute respiratory infections (ARIs) in Suzhou. Children with ARIs admitted to the Children's Hospital of Soochow University between 1 September 2021 and 31 December 2022 and subjected to 13 respiratory pathogen multiplex PCR assays were included in the study. We retrospectively collected demographic details, results of respiratory pathogen panel tests, and discharge diagnostic information of the participants, and described the age and seasonal distribution of respiratory pathogens and risk factors for developing pneumonia. A total of 10,396 children <16 years of age, including 5,905 males and 4,491 females, were part of the study. The positive rates of the 11 respiratory pathogen assays were 23.3% (human rhinovirus (HRV)), 15.9% (human respiratory syncytial virus (HRSV)), 10.5% (human metapneumovirus (HMPV)), 10.3% (human parainfluenza virus (HPIV)), 8.6% (mycoplasma pneumoniae (MP)), 5.8% (Boca), 3.5% (influenza A (InfA)), 2.9% (influenza B (InfB)), 2.7% (human coronavirus (HCOV)), 2.0% (adenovirus (ADV)), and 0.5% (Ch), respectively. Bocavirus and HPIV detection peaked during the period from September to November (autumn), and MP and HMPV peaked in the months of November and December. The peak of InfA detection was found to be in summer (July and August), whereas the InfB peak was observed to be in winter (December, January, and February). HRSV and HRV predominated in the <3 years age group. HRV and HMPV were common in the 3-6 years group, whereas MP was predominant in the ≥6 years group. MP (odds ratio (OR): 70.068, 95%CI: 32.665-150.298, < 0.01), HMPV (OR: 6.493, 95%CI: 4.802-8.780, < 0.01), Boca (OR: 3.300, 95%CI: 2.186-4.980, < 0.01), and HRSV (OR: 2.649, 95%CI: 2.089-3.358, < 0.01) infections were more likely to develop into pneumonia than the other pathogens. With the use of NPIs, HRV was the most common pathogen in children with ARIs, and MP was more likely to progress to pneumonia than other pathogens.
Topics: Child; Male; Female; Humans; Influenza, Human; Prevalence; Retrospective Studies; Pneumonia; Respiratory Tract Infections; Respiratory Syncytial Virus, Human; Metapneumovirus; China
PubMed: 37127406
DOI: 10.1017/S0950268823000626 -
Microbiology Spectrum Aug 2023Respiratory viruses may interfere with each other and affect the epidemic trend of the virus. However, the understanding of the interactions between respiratory viruses...
Respiratory viruses may interfere with each other and affect the epidemic trend of the virus. However, the understanding of the interactions between respiratory viruses at the population level is still very limited. We here conducted a prospective laboratory-based etiological study by enrolling 14,426 patients suffered from acute respiratory infection (ARI) in Beijing, China during 2005 to 2015. All 18 respiratory viruses were simultaneously tested for each nasal and throat swabs collected from enrolled patients using molecular tests. The virus correlations were quantitatively evaluated, and the respiratory viruses could be divided into two panels according to the positive and negative correlations. One included influenza viruses (IFVs) A, B, and respiratory syncytial virus (RSV), while the other included human parainfluenza viruses (HPIVs) 1/3, 2/4, adenovirus (Adv), human metapneumovirus (hMPV), and enterovirus (including rhinovirus, named picoRNA), α and β human coronaviruses (HCoVs). The viruses were positive-correlated in each panel, while negative-correlated between panels. After adjusting the confounding factors by vector autoregressive model, positive interaction between IFV-A and RSV and negative interaction between IFV-A and picoRNA are still be observed. The asynchronous interference of IFV-A significantly delayed the peak of β human coronaviruses epidemic. The binary property of the respiratory virus interactions provides new insights into the viral epidemic dynamics in human population, facilitating the development of infectious disease control and prevention strategies. Systematic quantitative assessment of the interactions between different respiratory viruses is pivotal for the prevention of infectious diseases and the development of vaccine strategies. Our data showed stable interactions among respiratory viruses at human population level, which are season irrelevant. Respiratory viruses could be divided into two panels according to their positive and negative correlations. One included influenza virus and respiratory syncytial virus, while the other included other common respiratory viruses. It showed negative correlations between the two panels. The asynchronous interference between influenza virus and β human coronaviruses significantly delayed the peak of β human coronaviruses epidemic. The binary property of the viruses indicated transient immunity induced by one kind of virus would play role on subsequent infection, which provides important data for the development of epidemic surveillance strategies.
Topics: Humans; Infant; Prospective Studies; Viruses; Respiratory Tract Infections; Respiratory Syncytial Virus, Human; Orthomyxoviridae
PubMed: 37378522
DOI: 10.1128/spectrum.00019-23 -
Pediatric Annals Mar 2024
Topics: Humans; Immunization; Vaccination; Respiratory Syncytial Virus, Human
PubMed: 38466331
DOI: 10.3928/19382359-20240214-01 -
Science Translational Medicine Jun 2022Respiratory syncytial virus (RSV) is a substantial cause of morbidity and mortality globally. A candidate RSV prefusion (pre-F)-stabilized subunit vaccine, DS-Cav1, has...
Respiratory syncytial virus (RSV) is a substantial cause of morbidity and mortality globally. A candidate RSV prefusion (pre-F)-stabilized subunit vaccine, DS-Cav1, has previously been shown to elicit potent and durable neutralizing activity in a phase 1 clinical trial in healthy adults. Here, we used fluorescently labeled probes and flow cytometry to evaluate the antigen specificity and phenotype of RSV F-specific B cells longitudinally after DS-Cav1 immunization. Peripheral blood mononuclear cells (PBMCs) collected at time points before the first immunization through the end of the trial at 44 weeks were assessed by flow cytometry. Our data demonstrate a rapid increase in the frequency of pre-F-specific IgG and IgA B cells after the first immunization and a modest increase after a second immunization at week 12. Nearly all F-specific B cells down-regulated CD21 and up-regulated the proliferation marker CD71 after the first immunization, with less pronounced activation after the second immunization. Memory B cells (CD27CD21) specific for pre-F remained elevated above baseline at 44 weeks after vaccination. DS-Cav1 vaccination also activated human metapneumovirus (HMPV) cross-reactive B cells capable of binding prefusion-stabilized HMPV F protein and increased HMPV F-binding antibodies and neutralizing activity for HMPV in some participants. In summary, vaccination with RSV pre-F resulted in the expansion and activation of RSV and HMPV F-specific B cells that were maintained above baseline for at least 10 months and could contribute to long-term pneumovirus immunity.
Topics: Antibodies, Neutralizing; Antibodies, Viral; Humans; Leukocytes, Mononuclear; Pneumovirus; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Viral Fusion Proteins
PubMed: 35731888
DOI: 10.1126/scitranslmed.abo5032 -
Shock (Augusta, Ga.) Jan 2017Immunosuppression renders the host increased susceptible for secondary infections. It is becoming increasingly clear that not only bacterial sepsis, but also respiratory... (Review)
Review
Immunosuppression renders the host increased susceptible for secondary infections. It is becoming increasingly clear that not only bacterial sepsis, but also respiratory viruses with both severe and mild disease courses such as influenza, respiratory syncytial virus, and the human rhinovirus may induce immunosuppression. In this review, the current knowledge on (mechanisms of) bacterial- and virus-induced immunosuppression and the accompanying susceptibility toward various secondary infections is described. In addition, the frequently encountered secondary pathogens and their preferred localizations are presented. Finally, future perspectives in the context of the development of diagnostic markers and possibilities for personalized therapy to improve the diagnosis and treatment of immunocompromised patients are discussed.
Topics: Coinfection; Humans; Immunocompromised Host; Influenza A virus; Intensive Care Units; Respiratory Syncytial Viruses
PubMed: 27517143
DOI: 10.1097/SHK.0000000000000731 -
Nature Reviews. Microbiology May 2022
Topics: Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 35233104
DOI: 10.1038/s41579-022-00717-w