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British Poultry Science Feb 20101. The use of vaccines is the main approach to control of the economically important poultry viral respiratory diseases infectious laryngotracheitis (ILT), avian... (Review)
Review
1. The use of vaccines is the main approach to control of the economically important poultry viral respiratory diseases infectious laryngotracheitis (ILT), avian metapneumovirus (aMPV) infections and infectious bronchitis (IB). This paper appraises the current methods of vaccine control in the light of the nature of each virus and epidemiological factors associated with each disease. 2. Infectious laryngotracheitis virus (ILTV) exists as a single type with a wide range of disease severity. It is a serious disease in certain regions of the world. Recent work has distinguished molecular differences between vaccine and field strains and vaccine virus can be a cause of disease. Vaccines have remained unaltered for many years but new ones are being developed to counter vaccine side effects and reversion and reactivation of latent virus. 3. Avian metapneumoviruses, the cause of turkey rhinotracheitis and respiratory disease in chickens exists as 4 subtypes, A, B, C and D. A and B are widespread and vaccines work well provided that accurate doses are given. Newer vaccine developments are designed to eliminate reversion and possibly counter the appearance of newer field strains which may break through established vaccine coverage. 4. IB presents the biggest problem of the three. Being an unstable RNA virus, part of the viral genome that codes for the S1 spike gene can undergo mutation and recombination so that important antigenic variants can appear irregularly which may evade existing vaccine protection. While conventional vaccines work well against homologous types, new strategies are needed to counter this instability. Molecular approaches involving tailoring viruses to suit field challenges are in progress. However, the simple use of two genetically different vaccines to protect against a wide range of heterologous types is now a widespread practice that is very effective. 5. None of the three diseases described can claim to be satisfactorily controlled and it remains to be seen whether the newer generations of vaccines will be more efficacious and cost effective. The importance of constant surveillance is emphasised and the testing of novel vaccines cannot be achieved without the use of vaccine-challenge experiments in poultry.
Topics: Animals; Herpesvirus 1, Gallid; Infectious bronchitis virus; Metapneumovirus; Poultry; Poultry Diseases; Respiratory Tract Diseases; Viral Vaccines; Virus Diseases
PubMed: 20390564
DOI: 10.1080/00071660903541378 -
Nature Jan 2020Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) cause severe respiratory diseases in infants and elderly adults. No vaccine or effective antiviral...
Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) cause severe respiratory diseases in infants and elderly adults. No vaccine or effective antiviral therapy currently exists to control RSV or HMPV infections. During viral genome replication and transcription, the tetrameric phosphoprotein P serves as a crucial adaptor between the ribonucleoprotein template and the L protein, which has RNA-dependent RNA polymerase (RdRp), GDP polyribonucleotidyltransferase and cap-specific methyltransferase activities. How P interacts with L and mediates the association with the free form of N and with the ribonucleoprotein is not clear for HMPV or other major human pathogens, including the viruses that cause measles, Ebola and rabies. Here we report a cryo-electron microscopy reconstruction that shows the ring-shaped structure of the polymerase and capping domains of HMPV-L bound to a tetramer of P. The connector and methyltransferase domains of L are mobile with respect to the core. The putative priming loop that is important for the initiation of RNA synthesis is fully retracted, which leaves space in the active-site cavity for RNA elongation. P interacts extensively with the N-terminal region of L, burying more than 4,016 Å of the molecular surface area in the interface. Two of the four helices that form the coiled-coil tetramerization domain of P, and long C-terminal extensions projecting from these two helices, wrap around the L protein in a manner similar to tentacles. The structural versatility of the four P protomers-which are largely disordered in their free state-demonstrates an example of a 'folding-upon-partner-binding' mechanism for carrying out P adaptor functions. The structure shows that P has the potential to modulate multiple functions of L and these results should accelerate the design of specific antiviral drugs.
Topics: Amino Acid Sequence; Animals; Cell Line; Cryoelectron Microscopy; Metapneumovirus; Models, Molecular; Phosphoproteins; Protein Binding; Protein Structure, Quaternary; RNA-Dependent RNA Polymerase
PubMed: 31698413
DOI: 10.1038/s41586-019-1759-1 -
Journal of Virology Jan 2022Human metapneumovirus (HMPV) causes severe respiratory diseases in young children. The HMPV RNA genome is encapsidated by the viral nucleoprotein (N), forming an RNA-N...
Human metapneumovirus (HMPV) causes severe respiratory diseases in young children. The HMPV RNA genome is encapsidated by the viral nucleoprotein (N), forming an RNA-N complex (N), which serves as the template for genome replication and mRNA transcription by the RNA-dependent RNA polymerase (RdRp). The RdRp is formed by the association of the large polymerase subunit (L), which has RNA polymerase, capping, and methyltransferase activities, and the tetrameric phosphoprotein (P). P plays a central role in the RdRp complex by binding to N and L, allowing the attachment of the L polymerase to the N template. During infection these proteins concentrate in cytoplasmic inclusion bodies (IBs) where viral RNA synthesis occurs. By analogy to the closely related pneumovirus respiratory syncytial virus (RSV), it is likely that the formation of IBs depends on the interaction between HMPV P and N, which has not been demonstrated yet. Here, we finely characterized the binding P-N interaction domains by using recombinant proteins, combined with a functional assay for the polymerase complex activity, and the study of the recruitment of these proteins to IBs by immunofluorescence. We show that the last 6 C-terminal residues of HMPV P are necessary and sufficient for binding to N and that P binds to the N-terminal domain of N (N), and we identified conserved N residues critical for the interaction. Our results allowed us to propose a structural model for the HMPV P-N interaction. Human metapneumovirus (HMPV) is a leading cause of severe respiratory infections in children but also affects human populations of all ages worldwide. Currently, no vaccine or efficient antiviral treatments are available for this pneumovirus. A better understanding of the molecular mechanisms involved in viral replication could help the design or discovery of specific antiviral compounds. In this work, we have investigated the interaction between two major viral proteins involved in HMPV RNA synthesis, the N and P proteins. We finely characterized their domains of interaction and identified a pocket on the surface of the N protein, a potential target of choice for the design of compounds interfering with N-P complexes and inhibiting viral replication.
Topics: Animals; Binding Sites; Cell Line; Cricetinae; Inclusion Bodies; Metapneumovirus; Models, Molecular; Mutation; Nucleocapsid Proteins; Phosphoproteins; Protein Binding; Protein Interaction Domains and Motifs; RNA, Viral; RNA-Dependent RNA Polymerase; Virus Replication
PubMed: 34730389
DOI: 10.1128/JVI.00909-21 -
Virus Research May 2024Human metapneumovirus(hMPV) is one of the most common viruses that cause acute lower respiratory tract infections. Interleukin-1β (IL-1β) has been reported to play an... (Review)
Review
BACKGROUND
Human metapneumovirus(hMPV) is one of the most common viruses that cause acute lower respiratory tract infections. Interleukin-1β (IL-1β) has been reported to play an important role in multiple virus replication. Patients with hMPV infection have increased levels of IL-1β which reminds IL-1β is associated with hMPV infection. However, the mechanism by which IL-1β affects hMPV replication remains unclear. In this study, we explore the effect of IL-1β on hMPV replication and investigate its specific mechanism of action.
METHODS
We established an hMPV infection model through Human bronchial epithelial cells (16HBE). qRT-PCR and Western Blot were used to detect the expression levels of IL-1β, cyclic GMP-AMP synthase (cGAS), and interferon stimulating factor (STING). Regulating IL-1β expression by small interfering RNA (siRNA) or exogenous supplementary to study the influence of hMPV replication. The selective cGAS inhibitor RU.521, G150, and STING inhibitor H-151 were utilized to detect hMPV replication in 16HBE cells.
RESULTS
The level of IL-1β protein increased in a time-dependent and dose-dependent manner after hMPV infection. The mRNA and protein levels of cGAS and STING were significantly up-regulated. Knockdown of IL-1β could contribute to the decreased viral loads of hMPV. While the exogenous supplement of recombinant human IL-1β in cells, replication of hMPV was significantly increased. Additionally, the level of cGAS-STING protein expression would be affected by regulating IL-1β expression. Inhibitors of the cGAS-STING pathway led to a lower level of hMPV replication.
CONCLUSION
This study found that IL-1β could promote hMPV replication through the cGAS-STING pathway, which has the potential to serve as a candidate to fight against hMPV infection, targeting IL-1β may be an effective new strategy to restrain virus replication.
Topics: Humans; Metapneumovirus; Interleukin-1beta; Signal Transduction; Nucleotidyltransferases; Interferons
PubMed: 38431054
DOI: 10.1016/j.virusres.2024.199344 -
Journal of Clinical Virology : the... Aug 2016This meta-analysis aimed to estimate the prevalence of human metapneumovirus (hMPV) infections in patients hospitalized for acute respiratory infection (ARI) and to... (Meta-Analysis)
Meta-Analysis Review
This meta-analysis aimed to estimate the prevalence of human metapneumovirus (hMPV) infections in patients hospitalized for acute respiratory infection (ARI) and to study factors associated with this prevalence. Medline and ScienceDirect databases were searched for prospective observational studies that screened hospitalized patients with ARI for hMPV by RT-PCR, with data available at December 27, 2014. The risk of bias was assessed regarding participation rate, definition of ARI, description of diagnostic technique, method of inclusion identical for all subjects, standardized and identical sampling method for all subjects, analysis performed according to the relevant subgroups, and presentation of data sources. Random-effect meta-analysis with arcsine transformation and meta-regressions was used. In the 75 articles included, the prevalence of hMPV among hospitalized ARI was 6.24% (95% CI 5.25-7.30). An effect of the duration of the inclusion period was observed (p=0.0114), with a higher prevalence of hMPV in studies conducted during periods of 7-11 months (10.56%, 95% CI 5.97-16.27) or complete years (7.55%, 95% CI 5.90-9.38) than in periods of 6 months or less (5.36%, 95% CI 4.29-6.54). A significant increase in the incidence with increasing distance from the equator was observed (p=0.0384). hMPV should be taken into account as a possible etiology in hospitalized ARI.
Topics: Hospitalization; Humans; Metapneumovirus; Paramyxoviridae Infections
PubMed: 27337518
DOI: 10.1016/j.jcv.2016.05.015 -
PloS One 2022In order to develop an appropriate method for high-throughput detection of avian metapneumovirus, a quadruple real-time reverse-transcription polymerase chain reaction...
In order to develop an appropriate method for high-throughput detection of avian metapneumovirus, a quadruple real-time reverse-transcription polymerase chain reaction assay was established with four pairs of specific primers and four specific probes based on the G or M gene of aMPV-A, aMPV-B, aMPV-C and aMPV-D. Its specificity and sensitivity were evaluated, and clinical samples were tested by the method. The results showed that all the four subgroups of avian metapneumovirus can be detected in the quadruple real-time RT-PCR assay simultaneously, with a detection limit of 100-1000 cRNA copies/reaction. The other common poultry viruses were negative. In the avian clinical sample detection, 39 out of 1920 clinical samples collected from 8 provinces were positive. Compared with published RT-PCR assays, the κ value of the quadruple real-time RT-PCR assay in 1920 avian clinical samples was 1.000 (P < 0.001). The established method could be used for the rapid detection of the four subgroups of avian metapneumovirus with high specificity and high sensitivity.
Topics: Animals; Birds; Metapneumovirus; Poultry Diseases; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity
PubMed: 35763505
DOI: 10.1371/journal.pone.0270708 -
Viruses Feb 2023RNA viruses are known to induce a wide variety of respiratory tract illnesses, from simple colds to the latest coronavirus pandemic, causing effects on public health and... (Review)
Review
RNA viruses are known to induce a wide variety of respiratory tract illnesses, from simple colds to the latest coronavirus pandemic, causing effects on public health and the economy worldwide. Influenza virus (IV), parainfluenza virus (PIV), metapneumovirus (MPV), respiratory syncytial virus (RSV), rhinovirus (RhV), and coronavirus (CoV) are some of the most notable RNA viruses. Despite efforts, due to the high mutation rate, there are still no effective and scalable treatments that accompany the rapid emergence of new diseases associated with respiratory RNA viruses. Host-directed therapies have been applied to combat RNA virus infections by interfering with host cell factors that enhance the ability of immune cells to respond against those pathogens. The reprogramming of immune cell metabolism has recently emerged as a central mechanism in orchestrated immunity against respiratory viruses. Therefore, understanding the metabolic signature of immune cells during virus infection may be a promising tool for developing host-directed therapies. In this review, we revisit recent findings on the immunometabolic modulation in response to infection and discuss how these metabolic pathways may be used as targets for new therapies to combat illnesses caused by respiratory RNA viruses.
Topics: Humans; Coronavirus; Coronavirus Infections; Enterovirus Infections; Metapneumovirus; RNA; Respiratory Syncytial Virus, Human
PubMed: 36851739
DOI: 10.3390/v15020525 -
The Journal of the American Board of... 2004Human metapneumovirus is an emerging human respiratory pathogen first discovered in 2001. It clinically resembles respiratory syncytial virus, can cause both upper and... (Review)
Review
Human metapneumovirus is an emerging human respiratory pathogen first discovered in 2001. It clinically resembles respiratory syncytial virus, can cause both upper and lower tract disease, and has been associated with serious illness in the young, among the immunosuppressed, and in the chronically ill. Cough and congestion are frequently reported, and respiratory failure may occur. Initial infection occurs during early childhood, and repeated infections throughout life impart only transient immunity. Diagnosis is by reverse transcription-polymerase chain reaction or rising serologic titers. No commercial laboratory tests or treatments are available. Primary care physicians should maintain vigilance for outbreaks of newly discovered and emerging respiratory illnesses.
Topics: Acute Disease; Communicable Diseases, Emerging; Humans; Metapneumovirus; Paramyxoviridae Infections; Respiratory Tract Infections
PubMed: 15575039
DOI: 10.3122/jabfm.17.6.466 -
Poultry Science Nov 2019Respiratory diseases like infectious bronchitis virus (IBV) and avian metapneumovirus (aMPV) have been held accountable for major losses for poultry production....
Respiratory diseases like infectious bronchitis virus (IBV) and avian metapneumovirus (aMPV) have been held accountable for major losses for poultry production. Nevertheless, scarce information was present dealing with the prevalence and molecular epidemiology of these infections in Greece and the efficacy of currently applied control strategies. To fill this gap, a specific epidemiological study was designed. A total of 106 broiler and layer farms, including 10 backyard and 96 commercial flocks, were sampled between March 2016 and May 2017, and the obtained tracheal swabs were tested for IBV and aMPV using RT-PCR based techniques followed by sequencing. For each farm, data regarding production type, flock features, clinical signs, and vaccination program were also recorded. Different associations between vaccination protocol, production type, animal category, birds density, age, presence of clinical signs, and IBV and/or aMPV infection were tested. Both IBV and aMPV field strain prevalence were proven high, approximately 20 and 30%, respectively, being the GI-19 lineage (14 out of 19; 73.6%) and B subtype (30 out of 30; 100%), the most commonly detected IBV and aMPV genetic types. Infection with IBV field strains was significantly associated with clinical sign presence (odds ratio = 8.55 [95CI = 2.17-42.90]). Remarkably, only the vaccination protocol involving a double vaccination at 1 D of age was proven protective against IBV-induced symptomatology, with the odds of developing disease being 4.14 [95CI = 1.34-14.51] times lower. No association was demonstrated between aMPV infection and clinical outbreaks or between aMPV and IBV detection, suggesting the marginal role of the former pathogen in poultry farming. Globally, the present study provides the first detailed investigation of the epidemiological scenario of 2 viruses traditionally considered of pivotal relevance in poultry farming and demonstrates that remarkable benefits could be obtained with just minor adjustments in vaccination protocols.
Topics: Animals; Chickens; Coronavirus Infections; Greece; Infectious bronchitis virus; Metapneumovirus; Molecular Epidemiology; Paramyxoviridae Infections; Poultry Diseases; Prevalence; Vaccination
PubMed: 31264704
DOI: 10.3382/ps/pez360 -
Tidsskrift For Den Norske Laegeforening... Oct 2005Human metapneumovirus (hMPV) is a pathogenic respiratory virus, discovered in 2001. The virus is part of the family paramyxoviridae and is comparatively closely related... (Review)
Review
Human metapneumovirus (hMPV) is a pathogenic respiratory virus, discovered in 2001. The virus is part of the family paramyxoviridae and is comparatively closely related to respiratory syncytial virus (RSV). The clinical manifestations of a hMPV infection are rather similar to infections caused by RSV, ranging from mild upper airway disease to severe pneumonia. Detection of hMPV RNA by polymerase chain reaction (PCR) is the only established routine diagnostic method. The virus is easily cultivated in several types of cell culture lines, however, cell pathology (cytopathic effect) is irregularly observed. Our department has developed an indirect immunofluorescence test based on polyvalent rabbit antibodies. This method appears to give reliable results, detecting hMPV both in cell culture and directly on patient samples. Nasopharyngeal aspirate is the preferred material for diagnostic purposes in small children. A nasopharyngeal swab, or alternatively a throat swab, can be used for older children and adults. Samples from lower airways are appropriate under special circumstances. Serology is not available for routine diagnostic use.
Topics: Adult; Animals; Child; Humans; Infant; Metapneumovirus; Paramyxoviridae Infections; Polymerase Chain Reaction; Rabbits; Respiratory Tract Infections
PubMed: 16244676
DOI: No ID Found