RESUMEN

BACKGROUND: Human metapneumovirus (HMPV) is a common respiratory pathogen that causes respiratory tract infections. In India, HMPV has been identified as one of the leading causes of morbidity and mortality in infants and young children with respiratory tract infections. The most reported sublineages of HMPV in India are B1, B2, A2b and A2c. OBJECTIVE: A retrospective study was conducted to determine the circulating genotypes of HMPV among SARI cases from January 2016 to December 2018. MATERIALS AND METHODS: Positive throat swab samples were confirmed with real-time RT-PCR. Subsequently, these samples were analysed using semi-nested conventional RT-PCR targeting the G gene, followed by sequencing and phylogenetic analysis. Clinical data analysis was also performed using SPSS 15.0 software. RESULTS: All 20 samples from the SARI cases were classified under the A2c sublineage of HMPV. Phylogenetic analysis indicated that these strains were genetically related to those circulating in Japan, China, and Croatia. Among the samples, ten showed 111-nucleotide duplications, while the other ten had 180-nucleotide duplications. CONCLUSION: Clinical analysis showed that four cases had coinfections with other pathogens. Our extensive analysis of patient samples determined that HMPV, especially the A2c genotype, significantly contributed to SARI cases within our study population, which signifies the importance of considering HMPV as a probable aetiological agent when investigating SARI outbreaks.

Asunto(s)

Genotipo , Metapneumovirus , Infecciones por Paramyxoviridae , Filogenia , Infecciones del Sistema Respiratorio , Humanos , Metapneumovirus/genética , Metapneumovirus/aislamiento & purificación , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/diagnóstico , Estudios Retrospectivos , Masculino , Femenino , Infecciones por Paramyxoviridae/epidemiología , Infecciones por Paramyxoviridae/virología , Lactante , Preescolar , India/epidemiología , Niño , Enfermedad Aguda , Reacción en Cadena en Tiempo Real de la Polimerasa

RESUMEN

A disease called "hydrosalpinx fluid and egg drop syndrome" (HFEDS) was observed in four flocks of Jinding ducks (Anas platyrhynchos domesticus) in Northeast China during the years 2022 to 2023. Here, we investigated the possible involvement of avian metapneumovirus (AMPV) infection. Full-length genome sequencing and sequence analysis of two AMPV strains showed that they belong to Eurasian lineage of AMPV subtype C. Based on surface glycoprotein (G) sequence comparisons, the Eurasian lineage can be divided into two sublineages (E1 and E2), and sublineage E2 is circulating in Jinding duck populations in Northeast China.

Asunto(s)

Patos , Genoma Viral , Metapneumovirus , Infecciones por Paramyxoviridae , Filogenia , Enfermedades de las Aves de Corral , Animales , Patos/virología , Metapneumovirus/genética , Metapneumovirus/clasificación , Metapneumovirus/aislamiento & purificación , Enfermedades de las Aves de Corral/virología , Infecciones por Paramyxoviridae/veterinaria , Infecciones por Paramyxoviridae/virología , China , Genoma Viral/genética , Secuenciación Completa del Genoma

RESUMEN

BACKGROUND: Co-detection of respiratory pathogens with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is poorly understood. This descriptive epidemiological study aimed to determine the effect of the interaction of different respiratory pathogens on clinical variables. METHODS: We retrospectively reviewed the results of comprehensive multiplex polymerase chain reaction (PCR) testing from November 2020 to March 2023 to estimate respiratory pathogen co-detection rates in Shinjuku, Tokyo. We evaluated the interactions of respiratory pathogens, particularly SARS-CoV-2, between observed and expected co-detection. We estimated the trend of co-detection with SARS-CoV-2 in terms of age and sex and applied a multiple logistic regression model adjusted for age, testing period, and sex to identify influencing factors between co-detection and single detection for each pathogen. RESULTS: Among 57,746 patients who underwent multiplex PCR testing, 10,516 (18.2%) had positive for at least one of the 22 pathogens. Additionally, 881 (1.5%) patients were confirmed to have a co-detection. SARS-CoV-2 exhibited negative interactions with adenovirus, coronavirus, human metapneumovirus, parainfluenza virus, respiratory syncytial virus, and rhino/enterovirus. SARS-CoV-2 co-detection with other pathogens occurred most frequently in patients of the youngest age group (0-4 years). A multiple logistic regression model indicated that younger age was the most influential factor for SARS-CoV-2 co-detection with other respiratory pathogens. CONCLUSION: The study highlights the prevalence of SARS-CoV-2 co-detection with other respiratory pathogens in younger age groups, necessitating further exploration of the clinical implications and severity of SARS-CoV-2 co-detection.

Asunto(s)

COVID-19 , Coinfección , Reacción en Cadena de la Polimerasa Multiplex , SARS-CoV-2 , Humanos , COVID-19/epidemiología , COVID-19/diagnóstico , Masculino , Persona de Mediana Edad , Femenino , Anciano , Adulto , Estudios Retrospectivos , Coinfección/epidemiología , Adolescente , Niño , Preescolar , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Lactante , Adulto Joven , Anciano de 80 o más Años , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Factores de Edad , Metapneumovirus/aislamiento & purificación , Metapneumovirus/genética , Tokio/epidemiología , Recién Nacido

RESUMEN

Human metapneumovirus (hMPV) is a respiratory pathogen that can cause lower respiratory tract infections and pneumonia in immunocompetent adults. Pneumonia caused by hMPV is reportedly more likely to cause bronchial wall thickening and ground-glass opacity (GGO). A 44-year-old woman with no significant medical history developed fever, cough, and nausea. Computed tomography of the chest showed scattered GGOs in the right upper lobe and infiltrating shadows with air bronchograms in the left lingual and bilateral lower lobes. The patient was admitted to our hospital for further evaluation. Atypical pneumonia was suspected and lascufloxacin (LSFX) was started. Multiplex polymerase chain reaction (PCR) detected hMPV on hospital day 2 using the FilmArray Respiratory Panel 2.1. Pneumonia due to hMPV was suspected and LSFX was discontinued. The patient subsequently showed spontaneous improvement and was discharged on hospital day 6 after admission. After discharge, pneumonia continued to improve. Early detection of respiratory pathogens using multiplex PCR can help determine the appropriate treatment strategy. As hMPV can also cause lobar pneumonia, we should consider pneumonia due to hMPV in the differential diagnosis of lobar pneumonia.

Asunto(s)

Metapneumovirus , Infecciones por Paramyxoviridae , Neumonía Viral , Tomografía Computarizada por Rayos X , Humanos , Metapneumovirus/aislamiento & purificación , Metapneumovirus/genética , Adulto , Femenino , Infecciones por Paramyxoviridae/diagnóstico , Infecciones por Paramyxoviridae/virología , Infecciones por Paramyxoviridae/tratamiento farmacológico , Neumonía Viral/diagnóstico , Neumonía Viral/virología , Neumonía Viral/tratamiento farmacológico , Reacción en Cadena de la Polimerasa Multiplex

RESUMEN

Objective: To investigate the genotype and epidemiological characteristics of human metapneumovirus (HMPV) among hospitalized cases with acute respiratory infections (ARI) in children in Changchun City, Jilin Province, China. Methods: From June 2019 to June 2023, throat swabs of ARI inpatients in Changchun Children's Hospital were collected, and their epidemiological and clinical information were also collected. Quantitative reverse transcription-PCR was used to identify HMPV-positive cases, followed by the amplification of the G gene and genetic analysis in the HMPV-positive cases. Results: A total of 3 311 children hospitalized with ARI were included in this study. Their age ranged from 0 to 17 years old, and the M (Q1, Q3) of age was 2 (1, 3) years. About 1 811 (54.70%) cases were males. A total of 167 HMPV-positive cases were detected with a positive rate of 5.04%, of which 92.81% (155/167) were children under 5 years old. The positive rate of HMPV in 2019 was 6.37% (30/471), which dropped to the lowest in 2020 (2.31%, 10/432). The HMPV-positive rate was then rebounded in 2021 (4.70%, 60/1 277) and 2022 (4.56%, 21/461), which increased to 6.87% (46/670) in 2023. The difference in HMPV-positive rate among each year was statistically significant (P<0.05). The prevalence peak of HMPV varied in different years, showing either a unimodal or bimodal distribution in one year. A total of 79 HMPV G gene sequences were obtained, of which subtype A and subtype B accounted for 48.10% and 51.90%, respectively. All of the subtype A sequences were clarified as A2c duplicated variants, and subtype B was mainly B2 genotype. Besides, subtypes A and B were prevalent alone or co-circulated in different years, and there was a subtype replacement pattern in HMPV. Conclusion: The positive rate of HMPV in hospitalized ARI cases in children is significantly different from 2019 to 2023 in Changchun City. Notably, there are certain switch patterns of HMPV subtypes A and B in different years.

Asunto(s)

Genotipo , Metapneumovirus , Infecciones por Paramyxoviridae , Infecciones del Sistema Respiratorio , Humanos , Metapneumovirus/genética , Metapneumovirus/clasificación , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Niño , Preescolar , Lactante , China/epidemiología , Masculino , Adolescente , Femenino , Infecciones por Paramyxoviridae/epidemiología , Infecciones por Paramyxoviridae/virología , Enfermedad Aguda , Hospitalización , Recién Nacido , Filogenia

RESUMEN

Human metapneumovirus (HMPV) is a common pathogen that can cause acute respiratory tract infections and is prevalent worldwide. There is yet no effective vaccine or specific treatment for HMPV. Early, rapid, and accurate detection is essential to treat the disease and control the spread of infection. In this study, we created the One-tube assay by combining Reverse Transcription-Recombinase Polymerase Amplification (RT-RPA) with the CRISPR/Cas12a system. By targeting the nucleoprotein (N) gene of HMPV to design specific primers and CRISPR RNAs (crRNAs), combining RT-RPA and CRISPR/Cas12a, established the One-tube assay. Meanwhile, the reaction conditions of the One-tube assay were optimized to achieve rapid and visual detection of HMPV. This assay could detect HMPV at 1 copy/µL in 30 min, without cross-reactivity with nine other respiratory pathogens. We validated the detection performance using clinical specimens and showed that the coincidence rate was 98.53 %，compared to the quantitative reverse-transcription polymerase chain reaction. The One-tube assay reduced the detection time and simplified the manual operation, while maintaining the detection performance and providing a new platform for HMPV detection.

Asunto(s)

Sistemas CRISPR-Cas , Metapneumovirus , Infecciones por Paramyxoviridae , Sensibilidad y Especificidad , Metapneumovirus/genética , Metapneumovirus/aislamiento & purificación , Humanos , Infecciones por Paramyxoviridae/diagnóstico , Infecciones por Paramyxoviridae/virología , ARN Viral/genética , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/diagnóstico , Técnicas de Amplificación de Ácido Nucleico/métodos

RESUMEN

Airborne animal viral pathogens can rapidly spread and become a global threat, resulting in substantial socioeconomic and health consequences. To prevent and control potential epidemic outbreaks, accurate, fast, and affordable point-of-care (POC) tests are essential. As a proof-of-concept, we have developed a molecular system based on the loop-mediated isothermal amplification (LAMP) technique for avian metapneumovirus (aMPV) detection, an airborne communicable agent mainly infecting turkeys and chickens. For this purpose, a colorimetric system was obtained by coupling the LAMP technique with specific DNA-functionalized AuNPs (gold nanoparticles). The system was validated using 50 different samples (pharyngeal swabs and tracheal tissue) collected from aMPV-infected and non-infected chickens and turkeys. Viral detection can be achieved in about 60 min with the naked eye, with 100% specificity and 87.88% sensitivity for aMPV. In summary, this novel molecular detection system allows suitable virus testing in the field, with accuracy and limit of detection (LOD) values highly close to qRT-PCR-based diagnosis. Furthermore, this system can be easily scalable to a platform for the detection of other viruses, addressing the current gap in the availability of POC tests for viral detection in poultry farming. KEY POINTS: •aMPV diagnosis using RT-LAMP is achieved with high sensitivity and specificity. •Fifty field samples have been visualized using DNA-nanoprobe validation. •The developed system is a reliable, fast, and cost-effective option for POCT.

Asunto(s)

Pollos , Oro , Metapneumovirus , Técnicas de Diagnóstico Molecular , Técnicas de Amplificación de Ácido Nucleico , Infecciones por Paramyxoviridae , Enfermedades de las Aves de Corral , Sensibilidad y Especificidad , Metapneumovirus/genética , Metapneumovirus/aislamiento & purificación , Animales , Técnicas de Amplificación de Ácido Nucleico/métodos , Técnicas de Amplificación de Ácido Nucleico/economía , Pollos/virología , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/economía , Infecciones por Paramyxoviridae/diagnóstico , Infecciones por Paramyxoviridae/veterinaria , Infecciones por Paramyxoviridae/virología , Enfermedades de las Aves de Corral/virología , Enfermedades de las Aves de Corral/diagnóstico , Oro/química , Pavos , Nanopartículas del Metal/química , Límite de Detección , Colorimetría/métodos , ADN Viral/genética

RESUMEN

The prefusion conformation of human metapneumovirus fusion protein (hMPV Pre-F) is critical for eliciting the most potent neutralizing antibodies and is the preferred immunogen for an efficacious vaccine against hMPV respiratory infections. Here we show that an additional cleavage event in the F protein allows closure and correct folding of the trimer. We therefore engineered the F protein to undergo double cleavage, which enabled screening for Pre-F stabilizing substitutions at the natively folded protomer interfaces. To identify these substitutions, we developed an AI convolutional classifier that successfully predicts complex polar interactions often overlooked by physics-based methods and visual inspection. The combination of additional processing, stabilization of interface regions and stabilization of the membrane-proximal stem, resulted in a Pre-F protein vaccine candidate without the need for a heterologous trimerization domain that exhibited high expression yields and thermostability. Cryo-EM analysis shows the complete ectodomain structure, including the stem, and a specific interaction of the newly identified cleaved C-terminus with the adjacent protomer. Importantly, the protein induces high and cross-neutralizing antibody responses resulting in near complete protection against hMPV challenge in cotton rats, making the highly stable, double-cleaved hMPV Pre-F trimer an attractive vaccine candidate.

Asunto(s)

Anticuerpos Neutralizantes , Anticuerpos Antivirales , Metapneumovirus , Proteínas Virales de Fusión , Vacunas Virales , Metapneumovirus/inmunología , Metapneumovirus/genética , Animales , Anticuerpos Neutralizantes/inmunología , Humanos , Anticuerpos Antivirales/inmunología , Proteínas Virales de Fusión/inmunología , Proteínas Virales de Fusión/química , Proteínas Virales de Fusión/genética , Vacunas Virales/inmunología , Infecciones por Paramyxoviridae/prevención & control , Infecciones por Paramyxoviridae/inmunología , Microscopía por Crioelectrón , Ingeniería de Proteínas/métodos , Sigmodontinae , Femenino , Multimerización de Proteína , Modelos Moleculares

RESUMEN

Viral co-infections are frequently observed among children, but whether specific viral interactions enhance or diminish the severity of respiratory disease is still controversial. This study aimed to investigate the type of viral mono- and co-infections by also evaluating viral correlations in 3525 respiratory samples from 3525 pediatric in/outpatients screened by the Allplex Respiratory Panel Assays and with a Severe Acute Respiratory Syndrome-COronaVirus 2 (SARS-CoV-2) test available. Overall, viral co-infections were detected in 37.8% of patients and were more frequently observed in specimens from children with lower respiratory tract infections compared to those with upper respiratory tract infections (47.1% vs. 36.0%, p = 0.003). SARS-CoV-2 and influenza A were more commonly detected in mono-infections, whereas human bocavirus showed the highest co-infection rate (87.8% in co-infection). After analyzing viral pairings using Spearman's correlation test, it was noted that SARS-CoV-2 was negatively associated with all other respiratory viruses, whereas a markedly significant positive correlation (p < 0.001) was observed for five viral pairings (involving adenovirus/human bocavirus/human enterovirus/metapneumoviruses/rhinovirus). The correlation between co-infection and clinical outcome may be linked to the type of virus(es) involved in the co-infection rather than simple co-presence. Further studies dedicated to this important point are needed, since it has obvious implications from a diagnostic and clinical point of view.

Asunto(s)

COVID-19 , Coinfección , Hospitales Pediátricos , Infecciones del Sistema Respiratorio , SARS-CoV-2 , Centros de Atención Terciaria , Humanos , Coinfección/epidemiología , Coinfección/virología , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/epidemiología , Italia/epidemiología , Preescolar , Niño , Lactante , Femenino , Masculino , Centros de Atención Terciaria/estadística & datos numéricos , COVID-19/epidemiología , COVID-19/virología , SARS-CoV-2/aislamiento & purificación , Adolescente , Bocavirus Humano/aislamiento & purificación , Bocavirus Humano/genética , Virosis/epidemiología , Virosis/virología , Hospitalización , Virus/aislamiento & purificación , Virus/clasificación , Virus/genética , Recién Nacido , Metapneumovirus/aislamiento & purificación , Metapneumovirus/genética

RESUMEN

PURPOSE: The objective of this study was to examine the molecular epidemiology and clinical characteristics of HMPV infection among children with ARIs in Nanjing. METHODS: The respiratory samples were collected from 2078 children (≤ 14 years) with acute respiratory infections and were tested for HMPV using real-time RT-PCR. Amplification and sequencing of the HMPV G gene were followed by phylogenetic analysis using MEGA 7.0. RESULT: The detection rate of HMPV among children was 4.7% (97/2078), with a concentration in those under 5 years of age. Notably, the peak season for HMPV prevalence was observed in winter. Among the 97 HMPV-positive samples, 51.5% (50/97) were available for characterization of the HMPV G protein gene. Phylogenetic analysis indicated that the sequenced HMPV strains were classified into three sublineages: A2c111nt - dup (84.0%), B1 (2.0%), and B2 (14.0%). CONCLUSION: There was an incidence of HMPV among hospitalized children during 2021-2022 in Nanjing with A2c111nt - dup being the dominant strain. This study demonstrated the molecular epidemiological characteristics of HMPV among children with respiratory infections in Nanjing, China.

Asunto(s)

Metapneumovirus , Epidemiología Molecular , Infecciones por Paramyxoviridae , Filogenia , Infecciones del Sistema Respiratorio , Estaciones del Año , Humanos , Metapneumovirus/genética , Metapneumovirus/clasificación , Metapneumovirus/aislamiento & purificación , China/epidemiología , Preescolar , Niño , Infecciones por Paramyxoviridae/epidemiología , Infecciones por Paramyxoviridae/virología , Lactante , Masculino , Femenino , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Adolescente , Incidencia , Recién Nacido , Prevalencia , Genotipo

RESUMEN

Acute respiratory infections are a major global burden in resource-limited countries, including countries in Africa. Although COVID-19 has been well studied since the pandemic emerged in Gabon, Central Africa, less attention has been paid to other respiratory viral diseases, and very little data are available. Herein, we provide the first data on the genetic diversity and detection of 18 major respiratory viruses in Gabon during the COVID-19 pandemic. Of 582 nasopharyngeal swab specimens collected from March 2020 to July 2021, which were SARS-CoV-2 negative, 156 were positive (26%) for the following viruses: enterovirus (20.3%), human rhinovirus (HRV) (4.6%), human coronavirus OC43 (1.2%), human adenovirus (0.9%), human metapneumovirus (hMPV) (0.5%), influenza A virus (IAV) (0.3%), and human parainfluenza viruses (0.5%). To determine the genetic diversity and transmission route of the viruses, phylogenetic analyses were performed using genome sequences of the detected viruses. The IAV strain detected in this study was genetically similar to strains isolated in the USA, whereas the hMPV strain belonging to the A2b subtype formed a cluster with Kenyan strains. This study provides the first complete genomic sequences of HRV, IAV, and hMPV detected in Gabon, and provides insight into the circulation of respiratory viruses in the country.

Asunto(s)

COVID-19 , Variación Genética , Filogenia , Infecciones del Sistema Respiratorio , Humanos , Gabón/epidemiología , COVID-19/epidemiología , COVID-19/virología , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/epidemiología , SARS-CoV-2/genética , SARS-CoV-2/clasificación , SARS-CoV-2/aislamiento & purificación , Masculino , Adulto , Femenino , Niño , Persona de Mediana Edad , Adolescente , Preescolar , Adulto Joven , Rhinovirus/genética , Rhinovirus/aislamiento & purificación , Rhinovirus/clasificación , Virus/genética , Virus/clasificación , Virus/aislamiento & purificación , Metapneumovirus/genética , Metapneumovirus/aislamiento & purificación , Metapneumovirus/clasificación , Genoma Viral , Nasofaringe/virología , Lactante , Anciano , Pandemias , Virus de la Influenza A/genética , Virus de la Influenza A/aislamiento & purificación , Virus de la Influenza A/clasificación

RESUMEN

OBJECTIVES: Human metapneumovirus (hMPV) and parainfluenza virus type 3 (PIV3) are common respiratory illnesses in children. The safety and immunogenicity of an investigational mRNA-based vaccine, mRNA-1653, encoding membrane-anchored fusion proteins of hMPV and PIV3, was evaluated in hMPV/PIV3-seropositive children. METHODS: In this phase 1b randomized, observer-blind, placebo-controlled, dose-ranging study, hMPV/PIV3-seropositive children were enrolled sequentially into 2 dose levels of mRNA-1653 administered 2 months apart; children aged 12 to 36 months were randomized (1:1) to receive 10-µg of mRNA-1653 or placebo and children aged 12 to 59 months were randomized (3:1) to receive 30-µg of mRNA-1653 or placebo. RESULTS: Overall, 27 participants aged 18 to 55 months were randomized; 15 participants received 10-µg of mRNA-1653 (n = 8) or placebo (n = 7), whereas 12 participants received 30-µg of mRNA-1653 (n = 9) or placebo (n = 3). mRNA-1653 was well-tolerated at both dose levels. The only reported solicited local adverse reaction was tenderness at injection site; solicited systemic adverse reactions included grade 1 or 2 chills, irritability, loss of appetite, and sleepiness. A single 10-µg or 30-µg mRNA-1653 injection increased hMPV and PIV3 neutralizing antibody titers (geometric mean fold-rise ratio over baseline: hMPV-A = 2.9-6.1; hMPV-B = 6.2-13.2; PIV3 = 2.8-3.0) and preF and postF binding antibody concentrations (geometric mean fold-rise ratio: hMPV preF = 5.3-6.1; postF = 4.6-6.5 and PIV3 preF = 13.9-14.2; postF = 11.0-12.1); a second injection did not further increase antibody levels in these seropositive children. Binding antibody responses were generally preF biased. CONCLUSIONS: mRNA-1653 was well-tolerated and boosted hMPV and PIV3 antibody levels in seropositive children aged 12 to 59 months, supporting the continued development of mRNA-1653 or its components for the prevention of hMPV and PIV3.

Asunto(s)

Virus de la Parainfluenza 3 Humana , Humanos , Femenino , Masculino , Preescolar , Lactante , Virus de la Parainfluenza 3 Humana/inmunología , Virus de la Parainfluenza 3 Humana/genética , Metapneumovirus/inmunología , Metapneumovirus/genética , Método Simple Ciego , Infecciones por Paramyxoviridae/prevención & control , Infecciones por Paramyxoviridae/inmunología , Anticuerpos Antivirales/sangre , Vacunas contra la Parainfluenza/inmunología , Vacunas contra la Parainfluenza/administración & dosificación , Vacunas contra la Parainfluenza/genética , Inmunogenicidad Vacunal , ARN Mensajero

RESUMEN

BACKGROUND: In the aftermath of the COVID-19 pandemic, there has been a surge in human metapneumovirus (HMPV) transmission, surpassing pre-epidemic levels. We aim to elucidate the clinical and epidemiological characteristics of HMPV infections in the post-COVID-19 pandemic era. METHODS: In this retrospective single-center study, participants diagnosed with laboratory confirmed HMPV infection through Targeted Next Generation Sequencing were included. The study encompassed individuals admitted to Henan Children's Hospital between April 29 and June 5, 2023. Demographic information, clinical records, and laboratory indicators were analyzed. RESULTS: Between April 29 and June 5, 2023, 96 pediatric patients were identified as infected with HMPV with a median age of 33.5 months (interquartile range, 12 ~ 48 months). The majority (87.5%) of infected children were under 5 years old. Notably, severe cases were statistically younger. Predominant symptoms included fever (81.3%) and cough (92.7%), with wheezing more prevalent in the severe group (56% vs 21.1%). Coinfection with other viruses was observed in 43 patients, with Epstein-Barr virus (EBV) (15.6%) or human rhinovirus A (HRV type A) (12.5%) being the most common. Human respiratory syncytial virus (HRSV) coinfection rate was significantly higher in the severe group (20% vs 1.4%). Bacterial coinfection occurred in 74 patients, with Haemophilus influenzae (Hin) and Streptococcus pneumoniae (SNP) being the most prevalent (52.1% and 41.7%, respectively). Severe patients demonstrated evidence of multi-organ damage. Noteworthy alterations included lower concentration of IL-12p70, decreased lymphocytes percentages, and elevated B lymphocyte percentages in severe cases, with statistical significance. Moreover, most laboratory indicators exhibited significant changes approximately 4 to 5 days after onset. CONCLUSIONS: Our data systemically elucidated the clinical and epidemiological characteristics of pediatric patients with HMPV infection, which might be instructive to policy development for the prevention and control of HMPV infection and might provide important clues for future HMPV research endeavors.

Asunto(s)

COVID-19 , Metapneumovirus , Infecciones por Paramyxoviridae , Humanos , China/epidemiología , Preescolar , Metapneumovirus/genética , Metapneumovirus/aislamiento & purificación , Estudios Retrospectivos , Femenino , Masculino , Lactante , Infecciones por Paramyxoviridae/epidemiología , Infecciones por Paramyxoviridae/virología , COVID-19/epidemiología , Niño , Coinfección/epidemiología , Coinfección/virología , SARS-CoV-2/genética

RESUMEN

Avian metapneumovirus (aMPV), classified within the Pneumoviridae family, wreaks havoc on poultry health. It typically causes upper respiratory tract and reproductive tract infections, mainly in turkeys, chickens, and ducks. Four subtypes of AMPV (A, B, C, D) and two unclassified subtypes have been identified, of which subtypes A and B are widely distributed across the world. In January 2024, an outbreak of severe respiratory disease occurred on turkey and chicken farms across different states in the US. Metagenomics sequencing of selected tissue and swab samples confirmed the presence of aMPV subtype B. Subsequently, all samples were screened using an aMPV subtype A and B multiplex real-time RT-PCR kit. Of the 221 farms, 124 (56%) were found to be positive for aMPV-B. All samples were negative for subtype A. Six whole genomes were assembled, five from turkeys and one from chickens; all six assembled genomes showed 99.29 to 99.98% nucleotide identity, indicating a clonal expansion event for aMPV-B within the country. In addition, all six sequences showed 97.74 to 98.58% nucleotide identity with previously reported subtype B sequences, e.g., VCO3/60616, Hungary/657/4, and BR/1890/E1/19. In comparison to these two reference strains, the study sequences showed unique 49-62 amino acid changes across the genome, with maximum changes in glycoprotein (G). One unique AA change from T (Threonine) to I (Isoleucine) at position 153 in G protein was reported only in the chicken aMPV sequence, which differentiated it from turkey sequences. The twelve unique AA changes along with change in polarity of the G protein may indicate that these unique changes played a role in the adaptation of this virus in the US poultry. This is the first documented report of aMPV subtype B in US poultry, highlighting the need for further investigations into its genotypic characterization, pathogenesis, and evolutionary dynamics.

Asunto(s)

Genoma Viral , Metapneumovirus , Infecciones por Paramyxoviridae , Filogenia , Enfermedades de las Aves de Corral , Pavos , Animales , Metapneumovirus/genética , Metapneumovirus/clasificación , Metapneumovirus/aislamiento & purificación , Infecciones por Paramyxoviridae/veterinaria , Infecciones por Paramyxoviridae/virología , Infecciones por Paramyxoviridae/epidemiología , Enfermedades de las Aves de Corral/virología , Enfermedades de las Aves de Corral/epidemiología , Pavos/virología , Estados Unidos/epidemiología , Pollos/virología , Aves de Corral/virología , Metagenómica , Brotes de Enfermedades/veterinaria

RESUMEN

This study aims to analyze the epidemiological and pathogenic characteristics of an outbreak primarily caused by respiratory syncytial virus (RSV), human rhinovirus (HRV), and human metapneumovirus (HMPV) in a kindergarten and primary school. The outbreak was investigated by field epidemiological investigation, and the common respiratory pathogens were screened by RT-PCR detection technology. The attack rate of this outbreak was 63.95% (110/172). Main symptoms included cough (85.45%), sore throat (60.91%), and sneezing (60.00%). Multifactorial logistic regression analysis revealed that continuous handwashing and mouth and nose covering when sneezing were protective factors. All 15 collected throat swab specimens tested positive for viruses, with HMPV as the predominant pathogen (80.00%), followed by HRV (53.33%), and two cases of positive respiratory syncytial virus (13.33%). Among them, six samples showed coinfections of HMPV and HRV, and one had coinfections of HMPV and RSV, resulting in a coinfection rate of 46.67%. Genetic sequencing indicated that the HMPV genotype in this outbreak was A2c, and the HRV genotype was type A, resulting in a coinfection outbreak of HMPV, HRV, and RSV in schools and kindergartens, suggesting that multi-pathogen surveillance of respiratory tract infections should be strengthened.

Asunto(s)

Coinfección , Brotes de Enfermedades , Metapneumovirus , Epidemiología Molecular , Infecciones por Virus Sincitial Respiratorio , Infecciones del Sistema Respiratorio , Humanos , China/epidemiología , Coinfección/epidemiología , Coinfección/virología , Masculino , Preescolar , Femenino , Niño , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/virología , Metapneumovirus/genética , Metapneumovirus/aislamiento & purificación , Genotipo , Rhinovirus/genética , Rhinovirus/aislamiento & purificación , Rhinovirus/clasificación , Filogenia , Infecciones por Paramyxoviridae/epidemiología , Infecciones por Paramyxoviridae/virología , Virus Sincitial Respiratorio Humano/genética , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Instituciones Académicas

RESUMEN

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.

Asunto(s)

Metapneumovirus , Infecciones por Paramyxoviridae , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Infecciones del Sistema Respiratorio , Salicilatos , Virosis , Niño , Adulto , Lactante , Humanos , Preescolar , Anciano , Metapneumovirus/genética , Virus Sincitial Respiratorio Humano/genética , Antivirales/farmacología , Antivirales/uso terapéutico

RESUMEN

Human metapneumovirus (HMPV) is a newly identified pathogen causing acute respiratory tract infections in young infants worldwide. Since the initial document of HMPV infection in China in 2003, Chinese scientists have made lots of efforts to prevent and control this disease, including developing diagnosis methods, vaccines and antiviral agents against HMPV, as well as conducting epidemiological investigations. However, effective vaccines or special antiviral agents against HMPV are currently not approved, thus developing early diagnosis methods and knowing its epidemiological characteristics will be beneficial for HMPV control. Here, we summarized current research focused on the epidemiological characteristics of HMPV in China and its available detection methods, which will be beneficial to increase the public awareness and disease control in the future.

Asunto(s)

Metapneumovirus , Infecciones por Paramyxoviridae , Infecciones del Sistema Respiratorio , Vacunas , Lactante , Humanos , Metapneumovirus/genética , Infecciones por Paramyxoviridae/diagnóstico , Infecciones por Paramyxoviridae/epidemiología , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/epidemiología , Antivirales , China/epidemiología

RESUMEN

Human metapneumovirus (HMPV) is a primary cause of acute respiratory infection, yet there are no approved vaccines or antiviral therapies for HMPV. Early host responses to HMPV are poorly characterized, and further understanding could identify important antiviral pathways. Type III interferon (IFN-λ) displays potent antiviral activity against respiratory viruses and is being investigated for therapeutic use. However, its role in HMPV infection remains largely unknown. Here, we show that IFN-λ is highly upregulated during HMPV infection in vitro in human and mouse airway epithelial cells and in vivo in mice. We found through several immunological and molecular assays that type II alveolar cells are the primary producers of IFN-λ. Using mouse models, we show that IFN-λ limits lung HMPV replication and restricts virus spread from upper to lower airways but does not contribute to clinical disease. Moreover, we show that IFN-λ signaling is predominantly mediated by CD45- non-immune cells. Mice lacking IFN-λ signaling showed diminished loss of ciliated epithelial cells and decreased recruitment of lung macrophages in early HMPV infection along with higher inflammatory cytokine and interferon-stimulated gene expression, suggesting that IFN-λ may maintain immunomodulatory responses. Administration of IFN-λ for prophylaxis or post-infection treatment in mice reduced viral load without inflammation-driven weight loss or clinical disease. These data offer clinical promise for IFN-λ in HMPV treatment. IMPORTANCE: Human metapneumovirus (HMPV) is a common respiratory pathogen and often contributes to severe disease, particularly in children, immunocompromised people, and the elderly. There are currently no licensed HMPV antiviral treatments or vaccines. Here, we report novel roles of host factor IFN-λ in HMPV disease that highlight therapeutic potential. We show that IFN-λ promotes lung antiviral responses by restricting lung HMPV replication and spread from upper to lower airways but does so without inducing lung immunopathology. Our data uncover recruitment of lung macrophages, regulation of ciliated epithelial cells, and modulation of inflammatory cytokines and interferon-stimulated genes as likely contributors. Moreover, we found these roles to be distinct and non-redundant, as they are not observed with knockout of, or treatment with, type I IFN. These data elucidate unique antiviral functions of IFN-λ and suggest IFN-λ augmentation as a promising therapeutic for treating HMPV disease and promoting effective vaccine responses.

Asunto(s)

Interferón lambda , Pulmón , Metapneumovirus , Infecciones por Paramyxoviridae , Replicación Viral , Animales , Humanos , Ratones , Antivirales/farmacología , Modelos Animales de Enfermedad , Células Epiteliales/virología , Células Epiteliales/inmunología , Interferón lambda/inmunología , Interferón lambda/farmacología , Interferones/inmunología , Interferones/farmacología , Pulmón/inmunología , Pulmón/virología , Metapneumovirus/inmunología , Metapneumovirus/genética , Ratones Endogámicos C57BL , Infecciones por Paramyxoviridae/inmunología , Infecciones por Paramyxoviridae/virología , Replicación Viral/efectos de los fármacos

RESUMEN

BACKGROUND: Human metapneumovirus(hMPV) is one of the most common viruses that cause acute lower respiratory tract infections. Interleukin-1ß (IL-1ß) has been reported to play an important role in multiple virus replication. Patients with hMPV infection have increased levels of IL-1ß which reminds IL-1ß is associated with hMPV infection. However, the mechanism by which IL-1ß affects hMPV replication remains unclear. In this study, we explore the effect of IL-1ß 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-1ß, cyclic GMP-AMP synthase (cGAS), and interferon stimulating factor (STING). Regulating IL-1ß 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-1ß 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-1ß could contribute to the decreased viral loads of hMPV. While the exogenous supplement of recombinant human IL-1ß in cells, replication of hMPV was significantly increased. Additionally, the level of cGAS-STING protein expression would be affected by regulating IL-1ß expression. Inhibitors of the cGAS-STING pathway led to a lower level of hMPV replication. CONCLUSION: This study found that IL-1ß 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-1ß may be an effective new strategy to restrain virus replication.

Asunto(s)

Metapneumovirus , Humanos , Metapneumovirus/genética , Interleucina-1beta/genética , Transducción de Señal/genética , Nucleotidiltransferasas/genética , Nucleotidiltransferasas/metabolismo , Interferones

RESUMEN

BACKGROUND: There has been high uptake of rapid antigen test device use for point-of-care COVID-19 diagnosis. Individuals who are symptomatic but test negative on COVID-19 rapid antigen test devices might have a different respiratory viral infection. We aimed to detect and sequence non-SARS-CoV-2 respiratory viruses from rapid antigen test devices, which could assist in the characterisation and surveillance of circulating respiratory viruses in the community. METHODS: We applied archival clinical nose and throat swabs collected between Jan 1, 2015, and Dec 31, 2022, that previously tested positive for a common respiratory virus (adenovirus, influenza, metapneumovirus, parainfluenza, rhinovirus, respiratory syncytial virus [RSV], or seasonal coronavirus; 132 swabs and 140 viral targets) on PCR to two commercially available COVID-19 rapid antigen test devices, the Panbio COVID-19 Ag Rapid Test Device and Roche SARS-CoV-2 Antigen Self-Test. In addition, we collected 31 COVID-19 rapid antigen test devices used to test patients who were symptomatic at The Royal Melbourne Hospital emergency department in Melbourne, Australia. We extracted total nucleic acid from the device paper test strips and assessed viral recovery using multiplex real-time PCR (rtPCR) and capture-based whole genome sequencing. Sequence and genome data were analysed through custom computational pipelines, including subtyping. FINDINGS: Of the 140 respiratory viral targets from archival samples, 89 (64%) and 88 (63%) were positive on rtPCR for the relevant taxa following extraction from Panbio or Roche rapid antigen test devices, respectively. Recovery was variable across taxa: we detected influenza A in nine of 18 samples from Panbio and seven of 18 from Roche devices; parainfluenza in 11 of 20 samples from Panbio and 12 of 20 from Roche devices; human metapneumovirus in 11 of 16 from Panbio and 14 of 16 from Roche devices; seasonal coronavirus in eight of 19 from Panbio and two of 19 from Roche devices; rhinovirus in 24 of 28 from Panbio and 27 of 28 from Roche devices; influenza B in four of 15 in both devices; and RSV in 16 of 18 in both devices. Of the 31 COVID-19 devices collected from The Royal Melbourne Hospital emergency department, 11 tested positive for a respiratory virus on rtPCR, including one device positive for influenza A virus, one positive for RSV, four positive for rhinovirus, and five positive for SARS-CoV-2. Sequences of target respiratory viruses from archival samples were detected in 55 (98·2%) of 56 samples from Panbio and 48 (85·7%) of 56 from Roche rapid antigen test devices. 98 (87·5%) of 112 viral genomes were completely assembled from these data, enabling subtyping for RSV and influenza viruses. All 11 samples collected from the emergency department had viral sequences detected, with near-complete genomes assembled for influenza A and RSV. INTERPRETATION: Non-SARS-CoV-2 respiratory viruses can be detected and sequenced from COVID-19 rapid antigen devices. Recovery of near full-length viral sequences from these devices provides a valuable opportunity to expand genomic surveillance programmes for public health monitoring of circulating respiratory viruses. FUNDING: Australian Government Medical Research Future Fund and Australian National Health and Medical Research Council.

Asunto(s)

COVID-19 , Gripe Humana , Metapneumovirus , Infecciones por Paramyxoviridae , Virus Sincitial Respiratorio Humano , Humanos , COVID-19/diagnóstico , SARS-CoV-2/genética , Gripe Humana/diagnóstico , Prueba de COVID-19 , Australia , Metapneumovirus/genética , Virus Sincitial Respiratorio Humano/genética , Secuenciación Completa del Genoma