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Clinical Reviews in Allergy & Immunology Dec 2013Respiratory syncytial virus (RSV) is amongst the most important pathogenic infections of childhood and is associated with significant morbidity and mortality. Although... (Review)
Review
Respiratory syncytial virus (RSV) is amongst the most important pathogenic infections of childhood and is associated with significant morbidity and mortality. Although there have been extensive studies of epidemiology, clinical manifestations, diagnostic techniques, animal models and the immunobiology of infection, there is not yet a convincing and safe vaccine available. The major histopathologic characteristics of RSV infection are acute bronchiolitis, mucosal and submucosal edema, and luminal occlusion by cellular debris of sloughed epithelial cells mixed with macrophages, strands of fibrin, and some mucin. There is a single RSV serotype with two major antigenic subgroups, A and B. Strains of both subtypes often co-circulate, but usually one subtype predominates. In temperate climates, RSV infections reflect a distinct seasonality with onset in late fall or early winter. It is believed that most children will experience at least one RSV infection by the age of 2 years. There are several key animal models of RSV. These include a model in mice and, more importantly, a bovine model; the latter reflects distinct similarity to the human disease. Importantly, the prevalence of asthma is significantly higher amongst children who are hospitalized with RSV in infancy or early childhood. However, there have been only limited investigations of candidate genes that have the potential to explain this increase in susceptibility. An atopic predisposition appears to predispose to subsequent development of asthma and it is likely that subsequent development of asthma is secondary to the pathogenic inflammatory response involving cytokines, chemokines and their cognate receptors. Numerous approaches to the development of RSV vaccines are being evaluated, as are the use of newer antiviral agents to mitigate disease. There is also significant attention being placed on the potential impact of co-infection and defining the natural history of RSV. Clearly, more research is required to define the relationships between RSV bronchiolitis, other viral induced inflammatory responses, and asthma.
Topics: Animals; Humans; Mice; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Respiratory Syncytial Viruses
PubMed: 23575961
DOI: 10.1007/s12016-013-8368-9 -
International Journal of Biological... 2021Respiratory syncytial virus (RSV) is one of the most important viral pathogens causing respiratory tract infection in infants, the elderly and people with poor immune... (Review)
Review
Respiratory syncytial virus (RSV) is one of the most important viral pathogens causing respiratory tract infection in infants, the elderly and people with poor immune function, which causes a huge disease burden worldwide every year. It has been more than 60 years since RSV was discovered, and the palivizumab monoclonal antibody, the only approved specific treatment, is limited to use for passive immunoprophylaxis in high-risk infants; no other intervention has been approved to date. However, in the past decade, substantial progress has been made in characterizing the structure and function of RSV components, their interactions with host surface molecules, and the host innate and adaptive immune response to infection. In addition, basic and important findings have also piqued widespread interest among researchers and pharmaceutical companies searching for effective interventions for RSV infection. A large number of promising monoclonal antibodies and inhibitors have been screened, and new vaccine candidates have been designed for clinical evaluation. In this review, we first briefly introduce the structural composition, host cell surface receptors and life cycle of RSV virions. Then, we discuss the latest findings related to the pathogenesis of RSV. We also focus on the latest clinical progress in the prevention and treatment of RSV infection through the development of monoclonal antibodies, vaccines and small-molecule inhibitors. Finally, we look forward to the prospects and challenges of future RSV research and clinical intervention.
Topics: Antiviral Agents; Genome, Viral; Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Viral Vaccines
PubMed: 34671221
DOI: 10.7150/ijbs.64762 -
Nature Reviews. Microbiology Apr 2019Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease in young children and elderly people. Although the virus was isolated in 1955, an... (Review)
Review
Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease in young children and elderly people. Although the virus was isolated in 1955, an effective RSV vaccine has not been developed, and the only licensed intervention is passive immunoprophylaxis of high-risk infants with a humanized monoclonal antibody. During the past 5 years, however, there has been substantial progress in our understanding of the structure and function of the RSV glycoproteins and their interactions with host cell factors that mediate entry. This period has coincided with renewed interest in developing effective interventions, including the isolation of potent monoclonal antibodies and small molecules and the design of novel vaccine candidates. In this Review, we summarize the recent findings that have begun to elucidate RSV entry mechanisms, describe progress on the development of new interventions and conclude with a perspective on gaps in our knowledge that require further investigation.
Topics: Antibodies, Monoclonal; Antiviral Agents; Clinical Trials as Topic; Host Microbial Interactions; Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Small Molecule Libraries; Viral Vaccines; Virus Internalization
PubMed: 30723301
DOI: 10.1038/s41579-019-0149-x -
Vaccine Jan 2017Human respiratory syncytial virus (hRSV) is a major cause of respiratory disease and hospitalisation of infants, worldwide, and is also responsible for significant... (Review)
Review
Human respiratory syncytial virus (hRSV) is a major cause of respiratory disease and hospitalisation of infants, worldwide, and is also responsible for significant morbidity in adults and excess deaths in the elderly. There is no licensed hRSV vaccine or effective therapeutic agent. However, there are a growing number of hRSV vaccine candidates that have been developed targeting different populations at risk of hRSV infection. Animal models of hRSV play an important role in the preclinical testing of hRSV vaccine candidates and although many have shown efficacy in preclinical studies, few have progressed to clinical trials or they have had only limited success. This is, at least in part, due to the lack of animal models that fully recapitulate the pathogenesis of hRSV infection in humans. This review summarises the strengths and limitations of animal models of hRSV, which include those in which hRSV is used to infect non-human mammalian hosts, and those in which non-human pneumoviruses, such as bovine (b)RSV and pneumonia virus of mice (PVM) are studied in their natural host. Apart from chimpanzees, other non-human primates (NHP) are only semi-permissive for hRSV replication and experimental infection with large doses of virus result in little or no clinical signs of disease, and generally only mild pulmonary pathology. Other animal models such as cotton rats, mice, ferrets, guinea pigs, hamsters, chinchillas, and neonatal lambs are also only semi-permissive for hRSV. Nevertheless, mice and cotton rats have been of value in the development of monoclonal antibody prophylaxis for infants at high risk of severe hRSV infection and have provided insights into mechanisms of immunity to and pathogenesis of hRSV. However, the extent to which they predict hRSV vaccine efficacy and safety is unclear and several hRSV vaccine candidates that are completely protective in rodent models are poorly effective in chimpanzees and other NHP, such as African Green monkeys. Furthermore, interpretation of findings from many rodent and NHP models of vaccine-enhanced hRSV disease has been confounded by sensitisation to non-viral antigens present in the vaccine and challenge virus. Studies of non-human pneumoviruses in their native hosts are more likely to reflect the pathogenesis of natural hRSV infection, and experimental infection of calves with bRSV and of mice with PVM result in clinical disease and extensive pulmonary pathology. These animal models have not only been of value in studies on mechanisms of immunity to and the pathogenesis of pneumovirus infections but have also been used to evaluate hRSV vaccine concepts. Furthermore, the similarities between the epidemiology of bRSV in calves and hRSV in infants and the high level of genetic and antigenic similarity between bRSV and hRSV, make the calf model of bRSV infection a relevant model for preclinical evaluation of hRSV vaccine candidates which contain proteins that are conserved between hRSV and bRSV.
Topics: Animals; Disease Models, Animal; Host-Pathogen Interactions; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses
PubMed: 27908639
DOI: 10.1016/j.vaccine.2016.11.054 -
Viruses Sep 2022Since the initial identification of respiratory syncytial virus (RSV) in 1956, much has been learned about the epidemiological impact and clinical manifestations of RSV...
Since the initial identification of respiratory syncytial virus (RSV) in 1956, much has been learned about the epidemiological impact and clinical manifestations of RSV infections [...].
Topics: Humans; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Respiratory Tract Infections
PubMed: 36298665
DOI: 10.3390/v14102110 -
Viruses Sep 2023Respiratory syncytial virus (RSV) infections are a constant public health problem, especially in infants and older adults. Virtually all children will have been infected... (Review)
Review
Respiratory syncytial virus (RSV) infections are a constant public health problem, especially in infants and older adults. Virtually all children will have been infected with RSV by the age of two, and reinfections are common throughout life. Since antigenic variation, which is frequently observed among other respiratory viruses such as SARS-CoV-2 or influenza viruses, can only be observed for RSV to a limited extent, reinfections may result from short-term or incomplete immunity. After decades of research, two RSV vaccines were approved to prevent lower respiratory tract infections in older adults. Recently, the FDA approved a vaccine for active vaccination of pregnant women to prevent severe RSV disease in infants during their first RSV season. This review focuses on the host response to RSV infections mediated by epithelial cells as the first physical barrier, followed by responses of the innate and adaptive immune systems. We address possible RSV-mediated immunomodulatory and pathogenic mechanisms during infections and discuss the current vaccine candidates and alternative treatment options.
Topics: Infant; Child; Female; Pregnancy; Humans; Aged; Respiratory Syncytial Virus Infections; Reinfection; Respiratory Syncytial Viruses; Immunity; Vaccines; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human
PubMed: 37896776
DOI: 10.3390/v15101999 -
Clinics in Chest Medicine Mar 2017Most viral respiratory tract infections are caused by classic respiratory viruses, including influenza, respiratory syncytial virus, human metapneumovirus,... (Review)
Review
Most viral respiratory tract infections are caused by classic respiratory viruses, including influenza, respiratory syncytial virus, human metapneumovirus, parainfluenza, rhinovirus, and adenovirus, whereas other viruses, such as herpes simplex, cytomegalovirus, and measles virus, can opportunistically affect the respiratory tract. The M2 inhibitors, amantadine and rimantadine, were historically effective for the prevention and treatment of influenza A but all circulating strains are currently resistant to these drugs. Neuraminidase inhibitors are the sole approved class of antivirals to treat influenza. Ribavirin, especially when combined with intravenous antibody, reduces morbidity and mortality among immunosuppressed patients.
Topics: Antiviral Agents; Humans; Influenza, Human; Respiratory Syncytial Viruses; Respiratory Tract Infections
PubMed: 28159156
DOI: 10.1016/j.ccm.2016.11.008 -
Virus Research Apr 2017The paramyxo- and pneumoviruses are members of the order Mononegavirales, a group of viruses with non-segmented, negative strand RNA genomes. The polymerases of these... (Review)
Review
The paramyxo- and pneumoviruses are members of the order Mononegavirales, a group of viruses with non-segmented, negative strand RNA genomes. The polymerases of these viruses are multi-functional complexes, capable of transcribing subgenomic capped and polyadenylated mRNAs and replicating the genome. Although there is no native structure available for any complete paramyxo- or pneumovirus polymerase, functional and structural studies of a fragment of a pneumovirus polymerase protein and mutation analyses and resistance profiling of small-molecule inhibitors have generated a wealth of mechanistic information. This review integrates these data with the structure of a related polymerase, identifying similarities, differences, gaps in knowledge, and avenues for antiviral drug development.
Topics: DNA Mutational Analysis; Drug Resistance, Viral; Mutation, Missense; Paramyxoviridae; Pneumovirus; RNA-Dependent RNA Polymerase; Transcription, Genetic; Virus Replication
PubMed: 28104450
DOI: 10.1016/j.virusres.2017.01.008 -
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