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Infectious Disorders Drug Targets Apr 2012Respiratory syncytial virus (RSV) is the major respiratory pathogen of infants and children worldwide, with no effective treatment or vaccine available. Steady progress... (Review)
Review
Respiratory syncytial virus (RSV) is the major respiratory pathogen of infants and children worldwide, with no effective treatment or vaccine available. Steady progress has been made in understanding the respiratory syncytial virus lifecycle and the consequences of infection, but some areas of RSV still remain poorly understood. Although many of the interactions between virus proteins that are required for efficient RSV assembly have been elucidated, many questions still remain regarding viral assembly, as well as the mechanisms of RSV budding. This review will summarise the current understanding of RSV assembly, including the various interactions between virus proteins and the involvement of cellular factors with a view to identifying possible attenuation and/or drug targets within the assembly pathway.
Topics: Child, Preschool; Humans; Infant; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Viral Proteins; Virus Assembly
PubMed: 22335497
DOI: 10.2174/187152612800100125 -
PloS One 2022Human and bovine respiratory syncytial virus (HRSV and BRSV) are closely genetically related and cause respiratory disease in their respective host. Whereas HRSV...
Human and bovine respiratory syncytial virus (HRSV and BRSV) are closely genetically related and cause respiratory disease in their respective host. Whereas HRSV vaccines are still under development, a multitude of BRSV vaccines are used to reduce clinical signs. To enable the design of vaccination protocols to entirely stop virus circulation, we aimed to investigate the duration, character and efficacy of the immune responses induced by natural infections. The systemic humoral immunity was monitored every two months during two years in 33 dairy cattle in different age cohorts following a natural BRSV outbreak, and again in selected individuals before and after a second outbreak, four years later. Local humoral and systemic cellular responses were also monitored, although less extensively. Based on clinical observations and economic losses linked to decreased milk production, the outbreaks were classified as moderate. Following the first outbreak, most but not all animals developed neutralising antibody responses, BRSV-specific IgG1, IgG2 and HRSV F- and HRSV N-reactive responses that lasted at least two years, and in some cases at least four years. In contrast, no systemic T cell responses were detected and only weak IgA responses were detected in some animals. Seronegative sentinels remained negative, inferring that no new infections occurred between the outbreaks. During the second outbreak, reinfections with clinical signs and virus shedding occurred, but the signs were milder, and the virus shedding was significantly lower than in naïve animals. Whereas the primary infection induced similar antibody titres against the prefusion and the post fusion form of the BRSV F protein, memory responses were significantly stronger against prefusion F. In conclusion, even if natural infections induce a long-lasting immunity, it would probably be necessary to boost memory responses between outbreaks, to stop the circulation of the virus and limit the potential role of previously infected adult cattle in the chain of BRSV transmission.
Topics: Adult; Animals; Antibodies, Neutralizing; Antibodies, Viral; Antibody Formation; Cattle; Cattle Diseases; Child, Preschool; Humans; Immunoglobulin A; Immunoglobulin G; Longitudinal Studies; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Bovine; Respiratory Syncytial Virus, Human
PubMed: 36112582
DOI: 10.1371/journal.pone.0274332 -
Brazilian Journal of Medical and... 2021Respiratory syncytial virus (RSV) infection is the main cause of lower respiratory tract infection in children. However, there is no effective treatment for RSV...
Respiratory syncytial virus (RSV) infection is the main cause of lower respiratory tract infection in children. However, there is no effective treatment for RSV infection. Here, we aimed to identify potential biomarkers to aid in the treatment of RSV infection. Children in the acute and convalescence phases of RSV infection were recruited and proteomic analysis was performed to identify differentially expressed proteins (DEPs). Subsequently, promising candidate proteins were determined by functional enrichment and protein-protein interaction network analysis, and underwent further validation by western blot both in clinical and mouse model samples. Among the 79 DEPs identified in RSV patient samples, 4 proteins (BPGM, TPI1, PRDX2, and CFL1) were confirmed to be significantly upregulated during RSV infection. Functional analysis showed that BPGM and TPI1 were mainly involved in glycolysis, indicating an association between RSV infection and the glycolysis metabolic pathway. Our findings provide insights into the proteomic profile during RSV infection and indicated that BPGM, TPI1, PRDX2, and CFL1 may be potential therapeutic biomarkers or targets for the treatment of RSV infection.
Topics: Biomarkers; Child; Humans; Proteomics; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 33656056
DOI: 10.1590/1414-431X20209850 -
Journal of Global Health Feb 2024
Topics: Adult; Humans; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections
PubMed: 38343348
DOI: 10.7189/jogh.14.03008 -
PeerJ 2023Respiratory diseases are among the major health problems causing a burden on hospitals. Diagnosis of infection and rapid prediction of severity without time-consuming...
Respiratory diseases are among the major health problems causing a burden on hospitals. Diagnosis of infection and rapid prediction of severity without time-consuming clinical tests could be beneficial in preventing the spread and progression of the disease, especially in countries where health systems remain incapable. Personalized medicine studies involving statistics and computer technologies could help to address this need. In addition to individual studies, competitions are also held such as Dialogue for Reverse Engineering Assessment and Methods (DREAM) challenge which is a community-driven organization with a mission to research biology, bioinformatics, and biomedicine. One of these competitions was the Respiratory Viral DREAM Challenge, which aimed to develop early predictive biomarkers for respiratory virus infections. These efforts are promising, however, the prediction performance of the computational methods developed for detecting respiratory diseases still has room for improvement. In this study, we focused on improving the performance of predicting the infection and symptom severity of individuals infected with various respiratory viruses using gene expression data collected before and after exposure. The publicly available gene expression dataset in the Gene Expression Omnibus, named GSE73072, containing samples exposed to four respiratory viruses (H1N1, H3N2, human rhinovirus (HRV), and respiratory syncytial virus (RSV)) was used as input data. Various preprocessing methods and machine learning algorithms were implemented and compared to achieve the best prediction performance. The experimental results showed that the proposed approaches obtained a prediction performance of 0.9746 area under the precision-recall curve (AUPRC) for infection (., shedding) prediction (SC-1), 0.9182 AUPRC for symptom class prediction (SC-2), and 0.6733 Pearson correlation for symptom score prediction (SC-3) by outperforming the best leaderboard scores of Respiratory Viral DREAM Challenge (a 4.48% improvement for SC-1, a 13.68% improvement for SC-2, and a 13.98% improvement for SC-3). Additionally, over-representation analysis (ORA), which is a statistical method for objectively determining whether certain genes are more prevalent in pre-defined sets such as pathways, was applied using the most significant genes selected by feature selection methods. The results show that pathways associated with the 'adaptive immune system' and 'immune disease' are strongly linked to pre-infection and symptom development. These findings contribute to our knowledge about predicting respiratory infections and are expected to facilitate the development of future studies that concentrate on predicting not only infections but also the associated symptoms.
Topics: Humans; Influenza A Virus, H3N2 Subtype; Influenza A Virus, H1N1 Subtype; Respiratory Syncytial Virus, Human; Virus Diseases; Machine Learning
PubMed: 37404475
DOI: 10.7717/peerj.15552 -
Scientific Reports Jun 2021Human respiratory syncytial viruses (RSVs) are classified into two major groups (A and B) based on antigenic differences in the G glycoprotein. To investigate...
Human respiratory syncytial viruses (RSVs) are classified into two major groups (A and B) based on antigenic differences in the G glycoprotein. To investigate circulating characteristics and phylodynamic history of RSV, we analyzed the genetic variability and evolutionary pattern of RSVs from 1977 to 2019 in this study. The results revealed that there was no recombination event of intergroup. Single nucleotide polymorphisms (SNPs) were observed through the genome with the highest occurrence rate in the G gene. Five and six sites in G protein of RSV-A and RSV-B, respectively, were further identified with a strong positive selection. The mean evolutionary rates for RSV-A and -B were estimated to be 1.48 × 10 and 1.92 × 10 nucleotide substitutions/site/year, respectively. The Bayesian skyline plot showed a constant population size of RSV-A and a sharp expansion of population size of RSV-B since 2005, and an obvious decrease 5 years later, then became stable again. The total population size of RSVs showed a similar tendency to that of RSV-B. Time-scaled phylogeny suggested a temporal specificity of the RSV-genotypes. Monitoring nucleotide changes and analyzing evolution pattern for RSVs could give valuable insights for vaccine and therapy strategies against RSV infection.
Topics: Bayes Theorem; Evolution, Molecular; Genes, Viral; Genetic Variation; Genotype; Humans; Phylogeny; Polymorphism, Single Nucleotide; RNA, Viral; Recombination, Genetic; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Selection, Genetic
PubMed: 34155268
DOI: 10.1038/s41598-021-92435-1 -
PLoS Pathogens Dec 2021It is generally thought that the promoters of non-segmented, negative strand RNA viruses (nsNSVs) direct the polymerase to initiate RNA synthesis exclusively opposite... (Comparative Study)
Comparative Study
It is generally thought that the promoters of non-segmented, negative strand RNA viruses (nsNSVs) direct the polymerase to initiate RNA synthesis exclusively opposite the 3´ terminal nucleotide of the genome RNA by a de novo (primer independent) initiation mechanism. However, recent studies have revealed that there is diversity between different nsNSVs with pneumovirus promoters directing the polymerase to initiate at positions 1 and 3 of the genome, and ebolavirus polymerases being able to initiate at position 2 on the template. Studies with other RNA viruses have shown that polymerases that engage in de novo initiation opposite position 1 typically have structural features to stabilize the initiation complex and ensure efficient and accurate initiation. This raised the question of whether different nsNSV polymerases have evolved fundamentally different structural properties to facilitate initiation at different sites on their promoters. Here we examined the functional properties of polymerases of respiratory syncytial virus (RSV), a pneumovirus, human parainfluenza virus type 3 (PIV-3), a paramyxovirus, and Marburg virus (MARV), a filovirus, both on their cognate promoters and on promoters of other viruses. We found that in contrast to the RSV polymerase, which initiated at positions 1 and 3 of its promoter, the PIV-3 and MARV polymerases initiated exclusively at position 1 on their cognate promoters. However, all three polymerases could recognize and initiate from heterologous promoters, with the promoter sequence playing a key role in determining initiation site selection. In addition to examining de novo initiation, we also compared the ability of the RSV and PIV-3 polymerases to engage in back-priming, an activity in which the promoter template is folded into a secondary structure and nucleotides are added to the template 3´ end. This analysis showed that whereas the RSV polymerase was promiscuous in back-priming activity, the PIV-3 polymerase generated barely detectable levels of back-primed product, irrespective of promoter template sequence. Overall, this study shows that the polymerases from these three nsNSV families are fundamentally similar in their initiation properties, but have differences in their abilities to engage in back-priming.
Topics: Animals; Cells, Cultured; Marburgvirus; Parainfluenza Virus 3, Human; RNA-Dependent RNA Polymerase; Respiratory Syncytial Viruses; Viral Replicase Complex Proteins
PubMed: 34914795
DOI: 10.1371/journal.ppat.1010151 -
CMAJ : Canadian Medical Association... Jan 2023
Topics: Humans; Infant; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses
PubMed: 36623860
DOI: 10.1503/cmaj.1096031 -
Influenza and Other Respiratory Viruses May 2020The epidemiology, clinical features, and resource utilization of respiratory syncytial virus (RSV) cases in the community and the hospital are not fully characterized.
BACKGROUND
The epidemiology, clinical features, and resource utilization of respiratory syncytial virus (RSV) cases in the community and the hospital are not fully characterized.
METHODS
We identified individuals of all ages with laboratory-confirmed RSV from two sources, a community cohort undergoing surveillance for acute respiratory infections (ARIs) and hospitalized patients from the same geographic area of New York City between 2013 and 15. The epidemiology, clinical features, and resource utilization (antibiotic/steroid/ribavirin usage, chest X-rays, respiratory-support (continuous positive airway pressure [CPAP], mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), and indicators of disease severity (respiratory-support, and/or ICU admission or death)) were compared among age groups using univariate and bivariate analyses.
RESULTS
In the community cohort (1777 people with 1805 ARIs), 66(3.7%) tested RSV-positive (3.8% of <1-year-olds; 3.8% of adults ≥65); 40.9% were medically attended, and 23.1% reported antibiotic usage. Among 40,461 tests performed on hospital patients, 2.7% were RSV-positive within ± 2 days of admission (37.3% <1 year old; 17.4% ≥65 years old). Among RSV-positive hospitalized adults ≥65%, 92.7%, 89.6% and 78.1% received a chest X-ray, antibiotics and/or steroids respectively, compared with 48.9%, 45.7%, and 48.7% of children <1. Severe illness occurred in 27.0% RSV-positive hospitalized <1-year-olds and 19.8% ≥65-year-olds.
CONCLUSIONS
Respiratory syncytial virus had a demonstrated impact in the community and hospital. Only 40% of RSV community cases were medically attended. In the hospitalized-cohort, <1- and ≥ 65-year-olds accounted for the majority of patients and had similar rates of severe illness. In addition, resource utilization was high in older adults, making both young children and older adults important potential RSV vaccine targets.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Female; Hospitalization; Humans; Infant; Male; Middle Aged; Residence Characteristics; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Retrospective Studies; United States; Young Adult
PubMed: 32077641
DOI: 10.1111/irv.12723 -
Journal of Global Health Jun 2019The high disease burden of respiratory syncytial virus (RSV) infection and renewed focus on developing a vaccine has led to sustained interest in published RSV-related... (Review)
Review
BACKGROUND
The high disease burden of respiratory syncytial virus (RSV) infection and renewed focus on developing a vaccine has led to sustained interest in published RSV-related research. The majority of this research comes from Europe and North/Central America and this landscape review aimed to identify and characterize RSV-related research published during 2011-2015 in these geographical areas.
METHODS
We conducted a literature review on electronic databases Scopus and Web of Science to identify published studies investigating RSV throughout Europe and North/Central America. We stratified RSV-related publications between 2011-2015 by study type, country, research institution and funding body.
RESULTS
The annual published output of RSV-related research has increased by 29% over the period 2011-2015. Eighty seven percent (13/15) of the most highly cited papers on RSV during this period were from North America. US universities with the highest number of RSV-related publications included Emory (n = 23), Vanderbilt (n = 23), University of Michigan (n = 21) and Ohio State (n = 20). The UK (n = 125), Netherlands (n = 97) and Spain (n = 76) were major European contributors to RSV-related publications. University Medical Centre Utrecht (n = 40) and Imperial College London (n = 28) were the European universities with the largest number of RSV-related publications. The National Institutes of Health provided funding for one quarter of all RSV-related publications. However, few countries in Eastern Europe, Central America and the Caribbean published RSV-related research. Few epidemiological studies focused on adult populations over 18 years old (n = 28, 7%) with only five publications specifically investigating elderly populations over 65.
CONCLUSIONS
This review identifies key regions and research institutions which contributed to RSV-related research during 2011-2015 as well as the donor agencies which supported this research. Further research investment is required in a number of countries. More research in the elderly and in high-risk adults is required given the lack of studies pertaining to these populations. Researchers and those commissioning research can use the data from this review to identify productive research institutions and geographical gaps in RSV research.
Topics: Biomedical Research; Central America; Europe; Humans; North America; Publications; Respiratory Syncytial Virus, Human
PubMed: 31131100
DOI: 10.7189/jogh.09.010425