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Virology Journal May 2021Human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) are leading causes of viral severe acute respiratory illnesses in childhood. Both the two viruses...
BACKGROUND
Human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) are leading causes of viral severe acute respiratory illnesses in childhood. Both the two viruses belong to the Pneumoviridae family and show overlapping clinical, epidemiological and transmission features. However, it is unknown whether these two viruses have similar geographic spread patterns which may inform designing and evaluating their epidemic control measures.
METHODS
We conducted comparative phylogenetic and phylogeographic analyses to explore the spatial-temporal patterns of HMPV and RSV across Africa using 232 HMPV and 842 RSV attachment (G) glycoprotein gene sequences obtained from 5 countries (The Gambia, Zambia, Mali, South Africa, and Kenya) between August 2011 and January 2014.
RESULTS
Phylogeographic analyses found frequently similar patterns of spread of RSV and HMPV. Viral sequences commonly clustered by region, i.e., West Africa (Mali, Gambia), East Africa (Kenya) and Southern Africa (Zambia, South Africa), and similar genotype dominance patterns were observed between neighbouring countries. Both HMPV and RSV country epidemics were characterized by co-circulation of multiple genotypes. Sequences from different African sub-regions (East, West and Southern Africa) fell into separate clusters interspersed with sequences from other countries globally.
CONCLUSION
The spatial clustering patterns of viral sequences and genotype dominance patterns observed in our analysis suggests strong regional links and predominant local transmission. The geographical clustering further suggests independent introduction of HMPV and RSV variants in Africa from the global pool, and local regional diversification.
Topics: Africa; Humans; Metapneumovirus; Paramyxoviridae Infections; Phylogeny; Phylogeography; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Spatio-Temporal Analysis
PubMed: 34051792
DOI: 10.1186/s12985-021-01570-8 -
Journal of Virology Dec 2017Human metapneumovirus (HMPV) causes significant upper and lower respiratory disease in all age groups worldwide. The virus possesses a negative-sense single-stranded RNA...
Human metapneumovirus (HMPV) causes significant upper and lower respiratory disease in all age groups worldwide. The virus possesses a negative-sense single-stranded RNA genome of approximately 13.3 kb encapsidated by multiple copies of the nucleoprotein (N), giving rise to helical nucleocapsids. In addition, copies of the phosphoprotein (P) and the large RNA polymerase (L) decorate the viral nucleocapsids. After viral attachment, endocytosis, and fusion mediated by the viral glycoproteins, HMPV nucleocapsids are released into the cell cytoplasm. To visualize the subsequent steps of genome transcription and replication, a fluorescence hybridization (FISH) protocol was established to detect different viral RNA subpopulations in infected cells. The FISH probes were specific for detection of HMPV positive-sense RNA (+RNA) and viral genomic RNA (vRNA). Time course analysis of human bronchial epithelial BEAS-2B cells infected with HMPV revealed the formation of inclusion bodies (IBs) from early times postinfection. HMPV IBs were shown to be cytoplasmic sites of active transcription and replication, with the translation of viral proteins being closely associated. Inclusion body formation was consistent with an actin-dependent coalescence of multiple early replicative sites. Time course quantitative reverse transcription-PCR analysis suggested that the coalescence of inclusion bodies is a strategy to efficiently replicate and transcribe the viral genome. These results provide a better understanding of the steps following HMPV entry and have important clinical implications. Human metapneumovirus (HMPV) is a recently discovered pathogen that affects human populations of all ages worldwide. Reinfections are common throughout life, but no vaccines or antiviral treatments are currently available. In this work, a spatiotemporal analysis of HMPV replication and transcription in bronchial epithelial cell-derived immortal cells was performed. HMPV was shown to induce the formation of large cytoplasmic granules, named inclusion bodies, for genome replication and transcription. Unlike other cytoplasmic structures, such as stress granules and processing bodies, inclusion bodies are exclusively present in infected cells and contain HMPV RNA and proteins to more efficiently transcribe and replicate the viral genome. Though inclusion body formation is nuanced, it corresponds to a more generalized strategy used by different viruses, including filoviruses and rhabdoviruses, for genome transcription and replication. Thus, an understanding of inclusion body formation is crucial for the discovery of innovative therapeutic targets.
Topics: Bronchi; Cell Line; Cytoplasm; DNA Replication; Epithelial Cells; Genome, Viral; Humans; In Situ Hybridization, Fluorescence; Inclusion Bodies, Viral; Metapneumovirus; RNA, Viral; Spatio-Temporal Analysis; Viral Proteins; Virus Replication
PubMed: 28978704
DOI: 10.1128/JVI.01282-17 -
The Netherlands Journal of Medicine Jun 2004In 2001, human metapneumovirus (hMPV) was discovered in young children with respiratory tract infection of unknown origin. In the two years since its discovery the...
In 2001, human metapneumovirus (hMPV) was discovered in young children with respiratory tract infection of unknown origin. In the two years since its discovery the dinical characteristics of this new virus have been darified. In children, especially those younger than one year of age, hMPV is responsible for 5 to 10% of respiratory tract infections requiring hospitalisation; its clinical course is somewhat milder, but otherwise indistinguishable from respiratory syncytial virus (RSV) infection. Human MPV can also be found in adults, in influenza-like illnesses, but also as a cause of pneumonia. Especially in the latter cases immunosuppressive conditions may be present.
Topics: Adult; Child; Humans; Infant; Metapneumovirus; Paramyxoviridae Infections; Respiratory Tract Infections
PubMed: 15460495
DOI: No ID Found -
Poultry Science Feb 2018With increasing frequency, avian Metapneumovirus (aMPV) is reported to induce respiratory signs in chickens. An adequate knowledge of current aMPV prevalence among...
With increasing frequency, avian Metapneumovirus (aMPV) is reported to induce respiratory signs in chickens. An adequate knowledge of current aMPV prevalence among Italian broilers is lacking, with little information available on its economical and health impact on the poultry industry. In order to collect preliminary data on the epidemiological context of aMPV in broiler flocks, a survey was performed in areas of Northern Italy with high poultry density from 2014 to 2016. Upper respiratory tract swabs were collected and processed by A and B subtype-specific multiplex real-time reverse transcription PCR (RT-PCR). Samples were also screened for infectious bronchitis virus (IBV) by generic RT-PCR and sequencing. Productive data and respiratory signs were detailed where possible. The high prevalence of aMPV was confirmed in broilers older than 26 d and also attested in IBV-negative farms. All aMPV detections belonged to subtype B. Italian strain genetic variability was evaluated by the partial attachment (G) gene sequencing of selected strains and compared with contemporary turkey strains and previously published aMPV references, revealing no host specificity and the progressive evolution of this virus in Italy.
Topics: Animals; Chickens; Italy; Metapneumovirus; Paramyxoviridae Infections; Poultry Diseases; Prevalence; Turkeys
PubMed: 29253264
DOI: 10.3382/ps/pex350 -
PloS One 2016Human metapneumovirus (HMPV) has been described as an important etiologic agent of upper and lower respiratory tract infections, especially in young children and the...
Human metapneumovirus (HMPV) has been described as an important etiologic agent of upper and lower respiratory tract infections, especially in young children and the elderly. Most of school-aged children might be introduced to HMPVs, and exacerbation with other viral or bacterial super-infection is common. However, our understanding of the molecular evolution of HMPVs remains limited. To address the comprehensive evolutionary dynamics of HMPVs, we report a genome-wide analysis of the eight genes (N, P, M, F, M2, SH, G, and L) using 103 complete genome sequences. Phylogenetic reconstruction revealed that the eight genes from one HMPV strain grouped into the same genetic group among the five distinct lineages (A1, A2a, A2b, B1, and B2). A few exceptions of phylogenetic incongruence might suggest past recombination events, and we detected possible recombination breakpoints in the F, SH, and G coding regions. The five genetic lineages of HMPVs shared quite remote common ancestors ranging more than 220 to 470 years of age with the most recent origins for the A2b sublineage. Purifying selection was common, but most protein genes except the F and M2-2 coding regions also appeared to experience episodic diversifying selection. Taken together, these suggest that the five lineages of HMPVs maintain their individual evolutionary dynamics and that recombination and selection forces might work on shaping the genetic diversity of HMPVs.
Topics: Evolution, Molecular; Genome, Viral; Humans; Metapneumovirus; Nasopharynx; Phylogeny; Recombination, Genetic
PubMed: 27046055
DOI: 10.1371/journal.pone.0152962 -
Influenza and Other Respiratory Viruses Nov 2022Human metapneumovirus (hMPV) is an important cause of pediatric respiratory infection. We leveraged the Nicaraguan Pediatric Influenza Cohort Study (NPICS) to assess the...
BACKGROUND
Human metapneumovirus (hMPV) is an important cause of pediatric respiratory infection. We leveraged the Nicaraguan Pediatric Influenza Cohort Study (NPICS) to assess the burden and seasonality of symptomatic hMPV infection in children.
METHODS
NPICS is an ongoing prospective study of children in Managua, Nicaragua. We assessed children for hMPV infection via real-time reverse-transcription polymerase chain reaction (RT-PCR). We used classical additive decomposition analysis to assess the temporal trends, and generalized growth models (GGMs) were used to estimate effective reproduction numbers.
RESULTS
From 2011 to 2016, there were 564 hMPV symptomatic infections, yielding an incidence rate of 5.74 cases per 100 person-years (95% CI 5.3, 6.2). Children experienced 3509 acute lower respiratory infections (ALRIs), of which 160 (4.6%) were associated with hMPV infection. Children under the age of one had 55% of all symptomatic hMPV infections (62/112) develop into hMPV-associated ALRIs and were five times as likely as children over one to have an hMPV-associated ALRI (rate ratio 5.5 95% CI 4.1, 7.4 p < 0.001). Additionally, symptomatic reinfection with hMPV was common. In total, 87 (15%) of all observed symptomatic infections were detected reinfections. The seasonality of symptomatic hMPV outbreaks varied considerably. From 2011 to 2016, four epidemic periods were observed, following a biennial seasonal pattern. The mean ascending phase of the epidemic periods were 7.7 weeks, with an overall mean estimated reproductive number of 1.2 (95% CI 1.1, 1.4).
CONCLUSIONS
Symptomatic hMPV infection was associated with substantial burden among children in the first year of life. Timing and frequency of symptomatic hMPV incidence followed biennial patterns.
Topics: Child; Cohort Studies; Humans; Infant; Influenza, Human; Metapneumovirus; Nicaragua; Paramyxoviridae Infections; Prospective Studies; Respiratory Tract Infections
PubMed: 35965382
DOI: 10.1111/irv.13034 -
The Journal of Infection Oct 2006Respiratory viruses are a common trigger for exacerbations of chronic obstructive pulmonary disease (COPD). Human metapneumovirus (hMPV) is a paramyxovirus associated...
OBJECTIVE
Respiratory viruses are a common trigger for exacerbations of chronic obstructive pulmonary disease (COPD). Human metapneumovirus (hMPV) is a paramyxovirus associated with respiratory tract infections and wheezing. Our aim was to determine whether hMPV was associated with exacerbations of COPD.
METHODS
The study was designed as an observational cohort study carried out in a 944-bed urban teaching hospital located in New Haven, Connecticut. Between December 2002 and May 2003, patients hospitalized due to an exacerbation of COPD were identified. Nasopharyngeal specimens obtained from these patients were tested for human metapneumovirus by RT-PCR and for respiratory syncytial virus, influenza A and B, parainfluenza-1, -2, and -3 and adenovirus by a cytospin-enhanced direct immunofluorescence assay and/or viral culture.
RESULTS
Fifty individuals met enrollment criteria and hMPV was identified in 6 (12%), respiratory syncytial virus in 4 (8%), influenza A in 2 (4%) and parainfluenza type 3 in 1 (2%) patients. Both A and B hMPV genotypes were identified in patients hospitalized due to exacerbations of COPD.
CONCLUSION
hMPV was frequently identified in patients hospitalized due to an exacerbation of COPD. Further studies are necessary to determine the epidemiology and the impact of hMPV in COPD patients.
Topics: Aged; Aged, 80 and over; Connecticut; Female; Hospitalization; Hospitals, Teaching; Hospitals, Urban; Humans; Male; Metapneumovirus; Middle Aged; Paramyxoviridae Infections; Phylogeny; Pulmonary Disease, Chronic Obstructive; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 16412516
DOI: 10.1016/j.jinf.2005.11.010 -
Journal of Clinical Virology : the... Jan 2006Some diagnostic, epidemiological and clinical features of the recently discovered human metapneumovirus remain to be investigated.
BACKGROUND
Some diagnostic, epidemiological and clinical features of the recently discovered human metapneumovirus remain to be investigated.
OBJECTIVES
To study the best approach for the diagnosis of human metapneumovirus infections by both conventional and molecular methods, along with the human metapneumovirus circulation rate in northern Italy and the severity of human metapneumovirus respiratory infections in a pediatric patient population.
STUDY DESIGN
Nasopharyngeal aspirates (NPA) were taken from 306 pediatric patients during the winter-spring season 2003-2004, and examined for conventional respiratory viruses by direct fluorescent staining and cell culture, while human coronavirus and human metapneumovirus were sought by RT-PCR.
RESULTS
RT-PCR detected human metapneumovirus in 40/306 (13.1%) children positive for respiratory viruses, with an incidence intermediate between that of respiratory syncytial virus (58 patients, 18.9%) and that of influenzavirus infections (29 patients, 9.5%). Phylogenetic analysis showed cocirculation of both human metapneumovirus types (A and B) as well as their relevant subtypes (A1-A2 and B1-B2). Clinically, human metapneumovirus was found to be second to human respiratory syncytial virus alone, as a cause of respiratory tract infections, while duration of virus excretion appeared to correlate with severity of infection, and virus load in NPA with the stage of respiratory infection.
CONCLUSION
(i) Human metapneumovirus is a major viral pathogen in the Italian pediatric patient population; (ii) the severity of lower respiratory tract infections approaches that of human respiratory syncytial virus; (iii) there are preliminary indications that the duration of virus excretion may reach 2-3 weeks and that the level of viral load in NPA correlates with the clinical stage of human metapneumovirus infection.
Topics: Animals; Cell Line; Child, Preschool; Humans; Incidence; Infant; Infant, Newborn; Italy; Metapneumovirus; Nasopharynx; Paramyxoviridae Infections; Phylogeny; Respiratory Tract Infections; Reverse Transcriptase Polymerase Chain Reaction; Seasons
PubMed: 16023411
DOI: 10.1016/j.jcv.2005.05.010 -
Scientific Reports Apr 2024The human respiratory syncytial virus (hRSV) and the human metapneumovirus (hMPV) are important human respiratory pathogens from the Pneumoviridae family. Both are...
The human respiratory syncytial virus (hRSV) and the human metapneumovirus (hMPV) are important human respiratory pathogens from the Pneumoviridae family. Both are responsible for severe respiratory tract infections in infants, young children, elderly individuals, adults with chronic medical conditions, and immunocompromised patients. Despite their large impact on human health, vaccines for hRSV were only recently introduced, and only limited treatment options exist. Here we show that Ginkgolic acid (GA), a natural compound from the extract of Ginkgo biloba, with known antiviral properties for several viruses, efficiently inhibits these viruses' infectivity and spread in cultures in a dose-dependent manner. We demonstrate that the drug specifically affects the entry step during the early stages on the viruses' life cycle with no effect on post-entry and late stage events, including viral gene transcription, genome replication, assembly and particles release. We provide evidence that GA acts as an efficient antiviral for members of the Pneumoviridae family and has the potential to be used to treat acute infections.
Topics: Child; Adult; Infant; Humans; Child, Preschool; Aged; Paramyxoviridae Infections; Metapneumovirus; Respiratory Tract Infections; Respiratory Syncytial Virus, Human; Virus Diseases; Respiratory Syncytial Virus Infections; Antiviral Agents; Salicylates
PubMed: 38589437
DOI: 10.1038/s41598-024-58032-8 -
MSphere Feb 2024Human metapneumovirus (HMPV), a member of the family, causes upper and lower respiratory tract infections in humans. studies with HMPV have mostly been performed in...
UNLABELLED
Human metapneumovirus (HMPV), a member of the family, causes upper and lower respiratory tract infections in humans. studies with HMPV have mostly been performed in monolayers of undifferentiated epithelial cells. studies in cynomolgus macaques and cotton rats have shown that ciliated epithelial cells are the main target of HMPV infection, but these observations cannot be studied in monolayer systems. Here, we established an organoid-derived bronchial culture model that allows physiologically relevant studies on HMPV. Inoculation with multiple prototype HMPV viruses and recent clinical virus isolates led to differences in replication among HMPV isolates. Prolific HMPV replication in this model caused damage to the ciliary layer, including cilia loss at advanced stages post-infection. These cytopathic effects correlated with those observed in previous studies with cynomolgus macaques. The assessment of the innate immune responses in three donors upon HMPV and RSV inoculation highlighted the importance of incorporating multiple donors to account for donor-dependent variation. In conclusion, these data indicate that the organoid-derived bronchial cell culture model resembles findings and is therefore a suitable and robust model for future HMPV studies.
IMPORTANCE
Human metapneumovirus (HMPV) is one of the leading causative agents of respiratory disease in humans, with no treatment or vaccine available yet. The use of primary epithelial cultures that recapitulate the tissue morphology and biochemistry of the human airways could aid in defining more relevant targets to prevent HMPV infection. For this purpose, this study established the first primary organoid-derived bronchial culture model suitable for a broad range of HMPV isolates. These bronchial cultures were assessed for HMPV replication, cellular tropism, cytopathology, and innate immune responses, where the observations were linked to previous studies with HMPV. This study exposed an important gap in the HMPV field since extensively cell-passaged prototype HMPV B viruses did not replicate in the bronchial cultures, underpinning the need to use recently isolated viruses with a controlled passage history. These results were reproducible in three different donors, supporting this model to be suitable to study HMPV infection.
Topics: Humans; Animals; Metapneumovirus; Cytology; Virus Replication; Paramyxoviridae Infections; Epithelium; Macaca; Tropism
PubMed: 38265200
DOI: 10.1128/msphere.00743-23