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Clinical Laboratory Jun 2023
Topics: Humans; Respiratory Syncytial Viruses; Seroepidemiologic Studies
PubMed: 37307110
DOI: 10.7754/Clin.Lab.2022.221109 -
Infectious Disorders Drug Targets Apr 2012
Topics: Antiviral Agents; Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Viral Vaccines
PubMed: 22335495
DOI: 10.2174/187152612800100134 -
Antiviral Chemistry & Chemotherapy 2019Human metapneumovirus, a paramyxovirus discovered in 2001, is a major cause of lower respiratory infection in adults and children worldwide. There are no licensed...
Human metapneumovirus, a paramyxovirus discovered in 2001, is a major cause of lower respiratory infection in adults and children worldwide. There are no licensed vaccines or drugs for human metapneumovirus. We developed a fluorescent, cell-based medium-throughput screening assay for human metapneumovirus that captures inhibitors of all stages of the viral lifecycle except budding of progeny virus particles from the cell membrane. We optimized and validated the assay and performed a successful medium-throughput screening. A number of hits were identified, several of which were confirmed to inhibit viral replication in secondary assays. This assay offers potential to discover new antivirals for human metapneumovirus and related respiratory viruses. Compounds discovered using the medium-throughput screening may also provide useful probes of viral biology.
Topics: Animals; Antiviral Agents; Cell Line; Drug Discovery; Drug Evaluation, Preclinical; Humans; Metapneumovirus; Microbial Sensitivity Tests; Respiratory Tract Infections; Serial Passage; Virus Replication
PubMed: 30759993
DOI: 10.1177/2040206619830197 -
Acta Paediatrica (Oslo, Norway : 1992) Dec 2017
Topics: Bronchiolitis; Bronchiolitis, Viral; Humans; Infant; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Syncytial Viruses
PubMed: 28945290
DOI: 10.1111/apa.14065 -
Journal of Molecular Biology Mar 2018RNA transcription of mononegavirales decreases gradually from the 3' leader promoter toward the 5' end of the genome, due to a decay in polymerase processivity. In the...
RNA transcription of mononegavirales decreases gradually from the 3' leader promoter toward the 5' end of the genome, due to a decay in polymerase processivity. In the respiratory syncytial virus and metapneumovirus, the M protein ensures transcription anti-termination. Despite being a homotetramer, respiratory syncytial virus M binds two molecules of RNA of 13mer or longer per tetramer, and temperature-sensitive secondary structure in the RNA ligand is unfolded by stoichiometric interaction with M. Fine quantitative analysis shows positive cooperativity, indicative of conformational asymmetry in the tetramer. RNA binds to M through a fast bimolecular association followed by slow rearrangements corresponding to an induced-fit mechanism, providing a sequential description of the time events of cooperativity. The first binding event of half of the RNA molecule to one of the sites increases the affinity of the second binding event on the adjacent contacting protomer by 15-fold, product of increased effective concentration caused by the entropic link. This mechanism allows for high-affinity binding with an otherwise relaxed sequence specificity, and instead suggests a yet undefined structural recognition signature in the RNA for modulating gene transcription. This work provides a basis for an essential event for understanding transcription antitermination in pneumoviruses and its counterpart Ebola virus VP30.
Topics: Carrier Proteins; Ebolavirus; Gene Expression Regulation, Viral; Genes, Viral; Kinetics; Metapneumovirus; Models, Molecular; Protein Conformation; RNA, Viral; RNA-Binding Proteins; Respiratory Syncytial Virus, Human; Transcription, Genetic; Viral Proteins; Virus Replication
PubMed: 29414675
DOI: 10.1016/j.jmb.2018.01.018 -
Springer Seminars in Immunopathology 1995
Review
Topics: Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses
PubMed: 8571168
DOI: 10.1007/BF00196165 -
The Journal of Infectious Diseases Sep 202225-hydroxyvitamin D (VD) effects on lung function and immune-modulation might affect respiratory syncytial virus (RSV) infection outcomes. We aimed to assess VD levels...
BACKGROUND
25-hydroxyvitamin D (VD) effects on lung function and immune-modulation might affect respiratory syncytial virus (RSV) infection outcomes. We aimed to assess VD levels on admission and their association with life-threatening RSV disease (LTD).
METHODS
A prospective cohort study was conducted during 2017-2019. Previously healthy infants aged <12 months, hospitalized with a first episode of RSV infection, were enrolled. LTD was defined by need for intensive care and ventilatory support. Serum VD levels <20 ng/mL were categorized as deficient, and 20-29.9 ng/mL as insufficient.
RESULTS
Of 125 patients studied, 73 (58%) were male. Median age was 4 months. Twenty-two patients developed LTD. No differences in viral load were seen between cases with LTD and controls (P = .94). Patients who developed LTD had significantly lower VD levels: median 18.4 ng/mL (IQR, 15.1-26.9 ng/mL) versus 31.7 ng/mL (IQR, 23.6-42.0 ng/mL), P < .001; 59% of infants with LTD had VD deficiency compared with 12% in those with better outcome. Multivariable regression analysis confirmed VD deficiency as a risk factor (odds ratio, 11.83; 95% confidence interval, 3.89-35.9; P < .001).
CONCLUSIONS
These findings provide additional evidence for the development of strategies to prevent severe RSV infections.
Topics: Female; Humans; Infant; Male; Prospective Studies; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Syncytial Viruses; Severity of Illness Index; Vitamin D
PubMed: 35106574
DOI: 10.1093/infdis/jiac033 -
Proceedings of the National Academy of... Jul 2013Human respiratory syncytial virus is a human pathogen that causes severe infection of the respiratory tract. Current information about the structure of the virus and its...
Human respiratory syncytial virus is a human pathogen that causes severe infection of the respiratory tract. Current information about the structure of the virus and its interaction with host cells is limited. We carried out an electron cryotomographic characterization of cell culture-grown human respiratory syncytial virus to determine the architecture of the virion. The particles ranged from 100 nm to 1,000 nm in diameter and were spherical, filamentous, or a combination of the two. The filamentous morphology correlated with the presence of a cylindrical matrix protein layer linked to the inner leaflet of the viral envelope and with local ordering of the glycoprotein spikes. Recombinant viruses with only the fusion protein in their envelope showed that these glycoproteins were predominantly in the postfusion conformation, but some were also in the prefusion form. The ribonucleocapsids were left-handed, randomly oriented, and curved inside the virions. In filamentous particles, they were often adjacent to an intermediate layer of protein assigned to M2-1 (an envelope-associated protein known to mediate association of ribonucleocapsids with the matrix protein). Our results indicate important differences in structure between the Paramyxovirinae and Pneumovirinae subfamilies within the Paramyxoviridae, and provide fresh insights into host cell exit of a serious pathogen.
Topics: Cell Line; Cryoelectron Microscopy; Electron Microscope Tomography; Humans; Protein Conformation; Respiratory Syncytial Virus, Human; Ribonucleoproteins; Viral Fusion Proteins
PubMed: 23776214
DOI: 10.1073/pnas.1309070110 -
Nature Communications May 2022Human metapneumovirus (hMPV) belongs to the Pneumoviridae family and is closely related to respiratory syncytial virus (RSV). The surface fusion (F) glycoprotein...
Human metapneumovirus (hMPV) belongs to the Pneumoviridae family and is closely related to respiratory syncytial virus (RSV). The surface fusion (F) glycoprotein mediates viral fusion and is the primary target of neutralizing antibodies against hMPV. Here we report 113 hMPV-F specific monoclonal antibodies (mAbs) isolated from memory B cells of human donors. We characterize the antibodies' germline usage, epitopes, neutralization potencies, and binding specificities. We find that unlike RSV-F specific mAbs, antibody responses to hMPV F are less dominant against the apex of the antigen, and the majority of the potent neutralizing mAbs recognize epitopes on the side of hMPV F. Furthermore, neutralizing epitopes that differ from previously defined antigenic sites on RSV F are identified, and multiple binding modes of site V and II mAbs are discovered. Interestingly, mAbs that bind preferentially to the unprocessed prefusion F show poor neutralization potency. These results elucidate the immune recognition of hMPV infection and provide novel insights for future hMPV antibody and vaccine development.
Topics: Antibodies, Monoclonal; Antibodies, Neutralizing; Antibodies, Viral; Epitopes; Humans; Memory B Cells; Metapneumovirus; Respiratory Syncytial Virus, Human; Viral Fusion Proteins
PubMed: 35538099
DOI: 10.1038/s41467-022-30205-x -
Antiviral Chemistry & Chemotherapy 2023Respiratory syncytial virus infections recur throughout life despite induction of immunity by the first natural infection. An effective vaccine has long been sought but...
Respiratory syncytial virus infections recur throughout life despite induction of immunity by the first natural infection. An effective vaccine has long been sought but no vaccine is currently licensed, although promising candidates are currently being developed based on greater knowledge of the virus properties. However, there are significant populations that may not be protected adequately by a vaccine or are unable to be vaccinated. Thus, there is a continued need for effective therapeutic agents to treat the infection, especially in higher-risk individuals, a perspective presented in this article.
Topics: Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Vaccines
PubMed: 37574755
DOI: 10.1177/20402066231194424