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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 -
Archivos de Bronconeumologia Apr 2022
Topics: Humans; Infant; Respiratory Syncytial Virus, Human
PubMed: 34226785
DOI: 10.1016/j.arbres.2021.06.007 -
Viruses Mar 2020Paramyxoviruses and pneumoviruses infect cells through fusion (F) protein-mediated merger of the viral envelope with target membranes. Members of these families include... (Review)
Review
Paramyxoviruses and pneumoviruses infect cells through fusion (F) protein-mediated merger of the viral envelope with target membranes. Members of these families include a range of major human and animal pathogens, such as respiratory syncytial virus (RSV), measles virus (MeV), human parainfluenza viruses (HPIVs), and highly pathogenic Nipah virus (NiV). High-resolution F protein structures in both the metastable pre- and the postfusion conformation have been solved for several members of the families and a number of F-targeting entry inhibitors have progressed to advanced development or clinical testing. However, small-molecule RSV entry inhibitors have overall disappointed in clinical trials and viral resistance developed rapidly in experimental settings and patients, raising the question of whether the available structural information may provide a path to counteract viral escape through proactive inhibitor engineering. This article will summarize current mechanistic insight into F-mediated membrane fusion and examine the contribution of structural information to the development of small-molecule F inhibitors. Implications are outlined for future drug target selection and rational drug engineering strategies.
Topics: Animals; Antiviral Agents; Binding Sites; Drug Discovery; Humans; Models, Molecular; Paramyxoviridae Infections; Paramyxovirinae; Pneumovirus; Pneumovirus Infections; Protein Binding; Structure-Activity Relationship; Virus Internalization
PubMed: 32245118
DOI: 10.3390/v12030342 -
Viruses Jul 2023Nosocomial pneumonia (NP) represents a leading cause of morbidity and mortality in hospitalized patients. Historically, clinicians have considered hospital-acquired... (Review)
Review
Nosocomial pneumonia (NP) represents a leading cause of morbidity and mortality in hospitalized patients. Historically, clinicians have considered hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), which comprise NP, to be essentially bacterial processes. As such, patients suspected of having either HAP or VAP are initially treated with broad-spectrum antibiotics, and few clinicians search for a possible culprit virus. Recent reports which build on earlier studies, however, indicate that viruses likely play an important role in NP. Studies employing viral diagnostics as part of the evaluation for NP indicate that common respiratory viruses can spread nosocomially and lead to HAP and VAP. Similarly, studies of the general epidemiology of respiratory viral infections, such as influenza, respiratory syncytial virus, adenovirus, and rhinovirus, confirm that these pathogens are important causes of NP, especially among immunosuppressed and pediatric patients. More importantly, these more contemporary analyses reveal that one cannot, based on clinical characteristics, distinguish a viral from a bacterial cause of NP. Additionally, viral HAP and VAP result in crude mortality rates that rival or exceed those reported in bacterial NP. Rigorous prospective, multicenter trials are needed to confirm the significance of respiratory viruses in NP, as are studies of novel therapeutics for these viral infections.
Topics: Humans; Child; Cross Infection; Prospective Studies; Healthcare-Associated Pneumonia; Adenoviridae; Respiratory Syncytial Virus, Human
PubMed: 37632017
DOI: 10.3390/v15081676 -
Viruses Dec 2020The paramyxo- and pneumovirus family includes a wide range of viruses that can cause respiratory and/or systemic infections in humans and animals. The significant... (Review)
Review
The paramyxo- and pneumovirus family includes a wide range of viruses that can cause respiratory and/or systemic infections in humans and animals. The significant disease burden of these viruses is further exacerbated by the limited therapeutics that are currently available. Host cellular proteins that can antagonize or limit virus replication are therefore a promising area of research to identify candidate molecules with the potential for host-targeted therapies. Host proteins known as host cell restriction factors are constitutively expressed and/or induced in response to virus infection and include proteins from interferon-stimulated genes (ISGs). Many ISG proteins have been identified but relatively few have been characterized in detail and most studies have focused on studying their antiviral activities against particular viruses, such as influenza A viruses and human immunodeficiency virus (HIV)-1. This review summarizes current literature regarding host cell restriction factors against paramyxo- and pneumoviruses, on which there is more limited data. Alongside discussion of known restriction factors, this review also considers viral countermeasures in overcoming host restriction, the strengths and limitations in different experimental approaches in studies reported to date, and the challenges in reconciling differences between in vitro and in vivo data. Furthermore, this review provides an outlook regarding the landscape of emerging technologies and tools available to study host cell restriction factors, as well as the suitability of these proteins as targets for broad-spectrum antiviral therapeutics.
Topics: Animals; Biomarkers; Gene Expression Regulation, Viral; Host Specificity; Host-Pathogen Interactions; Humans; Immunity, Innate; Paramyxoviridae Infections; Paramyxovirinae; Pneumovirus; Pneumovirus Infections; Viral Tropism; Virus Replication
PubMed: 33276587
DOI: 10.3390/v12121381 -
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 -
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 -
Cellular and Molecular Life Sciences :... Feb 2024The complement system, a key component of innate immunity, provides the first line of defense against bacterial infection; however, the COVID-19 pandemic has revealed... (Review)
Review
The complement system, a key component of innate immunity, provides the first line of defense against bacterial infection; however, the COVID-19 pandemic has revealed that it may also engender severe complications in the context of viral respiratory disease. Here, we review the mechanisms of complement activation and regulation and explore their roles in both protecting against infection and exacerbating disease. We discuss emerging evidence related to complement-targeted therapeutics in COVID-19 and compare the role of the complement in other respiratory viral diseases like influenza and respiratory syncytial virus. We review recent mechanistic studies and animal models that can be used for further investigation. Novel knockout studies are proposed to better understand the nuances of the activation of the complement system in respiratory viral diseases.
Topics: Animals; Humans; COVID-19; Pandemics; Complement System Proteins; Influenza, Human; Respiratory Syncytial Virus, Human
PubMed: 38368584
DOI: 10.1007/s00018-024-05157-8 -
Expert Review of Vaccines 2023Respiratory syncytial virus (RSV) infection is one of the most common causes of acute respiratory tract infections in young children and the elderly. Infants and young... (Review)
Review
INTRODUCTION
Respiratory syncytial virus (RSV) infection is one of the most common causes of acute respiratory tract infections in young children and the elderly. Infants and young children aged <2 years and the elderly are at particular risk of severe infections requiring hospitalization.
AREAS COVERED
This narrative review summarizes the epidemiology of RSV infection in Korea, with a particular focus on infants and the elderly, where possible, and highlights the need for effective vaccinations against RSV. Relevant papers were identified from a search of PubMed up to December 2021.
EXPERT OPINION
RSV infection is associated with a significant burden of illness in infants and the elderly worldwide and accounts for a substantial number of hospital admissions due to severe lower respiratory tract infections in both of these age groups in Korea. Vaccination has the potential to reduce the burden of acute RSV-associated disease and long-term consequences such as asthma. Increased understanding of the immune response to RSV, including mucosal immunity, and the innate and adaptive immune responses is needed. Technological advances in vaccine platforms could provide better approaches for achieving a safe and effective vaccine-induced immune response.
Topics: Infant; Aged; Child; Humans; Child, Preschool; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Immunization; Vaccination; Respiratory Syncytial Viruses; Respiratory Tract Infections; Immunity, Mucosal; Republic of Korea; Respiratory Syncytial Virus, Human
PubMed: 36960592
DOI: 10.1080/14760584.2023.2189459