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The Lancet. Microbe Sep 2023Human metapneumovirus (hMPV) is one of the leading causes of respiratory infection. Since its discovery in 2001, no specific antiviral or vaccine has been available in... (Review)
Review
Human metapneumovirus (hMPV) is one of the leading causes of respiratory infection. Since its discovery in 2001, no specific antiviral or vaccine has been available in contrast to its closely related family member human respiratory syncytial virus (hRSV). Neutralising monoclonal antibodies (nMAbs) are the core effectors of vaccines and are essential therapeutic immune drugs against infectious pathogens. The development of nMAbs against hMPV has accelerated in recent years as a result of breakthroughs in viral fusion (F) protein structural biology and experience with hRSV and other enveloped viruses. We provide an overview of the potent F-specific nMAbs of hMPV, generalise their targeting F antigen epitopes, and discuss the nMAb development strategy and future directions for hMPV and broad-spectrum hMPV, hRSV nMabs, and vaccine research and development.
PubMed: 37499668
DOI: 10.1016/S2666-5247(23)00134-9 -
Emerging Infectious Diseases Feb 2022Multiple respiratory viruses can concurrently or sequentially infect the respiratory tract and lead to virus‒virus interactions. Infection by a first virus could... (Review)
Review
Multiple respiratory viruses can concurrently or sequentially infect the respiratory tract and lead to virus‒virus interactions. Infection by a first virus could enhance or reduce infection and replication of a second virus, resulting in positive (additive or synergistic) or negative (antagonistic) interaction. The concept of viral interference has been demonstrated at the cellular, host, and population levels. The mechanisms involved in viral interference have been evaluated in differentiated airway epithelial cells and in animal models susceptible to the respiratory viruses of interest. A likely mechanism is the interferon response that could confer a temporary nonspecific immunity to the host. During the coronavirus disease pandemic, nonpharmacologic interventions have prevented the circulation of most respiratory viruses. Once the sanitary restrictions are lifted, circulation of seasonal respiratory viruses is expected to resume and will offer the opportunity to study their interactions, notably with severe acute respiratory syndrome coronavirus 2.
Topics: Animals; COVID-19; Humans; Pandemics; Respiratory Tract Infections; SARS-CoV-2; Viral Interference; Viruses
PubMed: 35075991
DOI: 10.3201/eid2802.211727 -
EMBO Molecular Medicine Apr 2022In virology, the term seasonality describes variations in virus prevalence at more or less regular intervals throughout the year. Specifically, it has long been...
In virology, the term seasonality describes variations in virus prevalence at more or less regular intervals throughout the year. Specifically, it has long been recognized that outbreaks of human influenza viruses, respiratory syncytial virus (RSV), and human coronaviruses occur in temperate climates during the winter season, whereas low activity is detected during the summer months. Other human respiratory viruses, such as parainfluenza viruses, human metapneumoviruses, and rhinoviruses, show highest activity during the spring or fall season in temperate regions, depending on the virus and subtype. In tropical climates, influenza viruses circulate throughout the year and no distinct seasonal patterns are observed, although virus outbreaks tend to spike during the rainy season. Overall, seasonality is more pronounced with greater distance from the equator, and tends to be less pronounced in regions closer to the equator (Li et al, 2019).
Topics: Humans; Influenza, Human; Metapneumovirus; Orthomyxoviridae; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Viruses
PubMed: 35157360
DOI: 10.15252/emmm.202115352 -
Nature Communications Mar 2022The human metapneumovirus (hMPV) fusion (F) protein is essential for viral entry and is a key target of neutralizing antibodies and vaccine development. The prefusion...
The human metapneumovirus (hMPV) fusion (F) protein is essential for viral entry and is a key target of neutralizing antibodies and vaccine development. The prefusion conformation is thought to be the optimal vaccine antigen, but previously described prefusion F proteins expressed poorly and were not well stabilized. Here, we use structures of hMPV F to guide the design of 42 variants containing stabilizing substitutions. Through combinatorial addition of disulfide bonds, cavity-filling substitutions, and improved electrostatic interactions, we describe a prefusion-stabilized F protein (DS-CavEs2) that expresses at 15 mg/L and has a melting temperature of 71.9 °C. Crystal structures of two prefusion-stabilized hMPV F variants reveal that antigenic surfaces are largely unperturbed. Importantly, immunization of mice with DS-CavEs2 elicits significantly higher neutralizing antibody titers against hMPV A1 and B1 viruses than postfusion F. The improved properties of DS-CavEs2 will advance the development of hMPV vaccines and the isolation of therapeutic antibodies.
Topics: Animals; Antibodies, Neutralizing; Antibodies, Viral; Humans; Immunization; Metapneumovirus; Mice; Viral Fusion Proteins
PubMed: 35288548
DOI: 10.1038/s41467-022-28931-3 -
Poultry Science May 2023Many pathogens that cause chronic diseases in birds use the respiratory tract as a primary route of infection, and respiratory disorders are the main leading source of... (Review)
Review
Many pathogens that cause chronic diseases in birds use the respiratory tract as a primary route of infection, and respiratory disorders are the main leading source of financial losses in the poultry business. Respiratory infections are a serious problem facing the poultry sector, causing severe economic losses. Avian influenza virus, Newcastle disease virus, infectious bronchitis virus, and avian pneumovirus are particularly serious viral respiratory pathogens. Mycoplasma gallisepticum, Staphylococcus, Bordetella avium, Pasteurella multocida, Riemerella anatipestifer, Chlamydophila psittaci, and Escherichia coli have been identified as the most serious bacterial respiratory pathogens in poultry. This review gives an updated summary, incorporating the latest data, about the evidence for the circulation of widespread, economically important poultry respiratory pathogens, with special reference to possible methods for the control and prevention of these pathogens.
Topics: Animals; Chickens; Bacterial Infections; Poultry; Respiratory Tract Infections; Metapneumovirus; Poultry Diseases
PubMed: 36965253
DOI: 10.1016/j.psj.2023.102553 -
Clinical Infectious Diseases : An... Aug 2022To combat the coronavirus disease 2019 (COVID-19) pandemic, nonpharmaceutical interventions (NPIs) were implemented worldwide, which impacted a broad spectrum of acute... (Observational Study)
Observational Study
BACKGROUND
To combat the coronavirus disease 2019 (COVID-19) pandemic, nonpharmaceutical interventions (NPIs) were implemented worldwide, which impacted a broad spectrum of acute respiratory infections (ARIs).
METHODS
Etiologically diagnostic data from 142 559 cases with ARIs, who were tested for 8 viral pathogens (influenza virus [IFV], respiratory syncytial virus [RSV], human parainfluenza virus [HPIV], human adenovirus [HAdV], human metapneumovirus [HMPV], human coronavirus [HCoV], human bocavirus [HBoV], and human rhinovirus [HRV]) between 2012 and 2021, were analyzed to assess the changes in respiratory infections in China during the first COVID-19 pandemic year compared with pre-pandemic years.
RESULTS
Test-positive rates of all respiratory viruses decreased during 2020, compared to the average levels during 2012-2019, with changes ranging from -17.2% for RSV to -87.6% for IFV. Sharp decreases mostly occurred between February and August when massive NPIs remained active, although HRV rebounded to the historical level during the summer. While IFV and HMPV were consistently suppressed year-round, RSV, HPIV, HCoV, HRV, and HBoV resurged and went beyond historical levels during September 2020-January 2021, after NPIs were largely relaxed and schools reopened. Resurgence was more prominent among children <18 years and in northern China. These observations remain valid after accounting for seasonality and long-term trend of each virus.
CONCLUSIONS
Activities of respiratory viral infections were reduced substantially in the early phases of the COVID-19 pandemic, and massive NPIs were likely the main driver. Lifting of NPIs can lead to resurgence of viral infections, particularly in children.
Topics: COVID-19; Child; Human bocavirus; Humans; Metapneumovirus; Orthomyxoviridae; Pandemics; Parainfluenza Virus 1, Human; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Virus Diseases; Viruses
PubMed: 34788811
DOI: 10.1093/cid/ciab942 -
MMWR. Morbidity and Mortality Weekly... Oct 2022The New Vaccine Surveillance Network (NVSN) is a prospective, active, population-based surveillance platform that enrolls children with acute respiratory illnesses...
The New Vaccine Surveillance Network (NVSN) is a prospective, active, population-based surveillance platform that enrolls children with acute respiratory illnesses (ARIs) at seven pediatric medical centers. ARIs are caused by respiratory viruses including influenza virus, respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human parainfluenza viruses (HPIVs), and most recently SARS-CoV-2 (the virus that causes COVID-19), which result in morbidity among infants and young children (1-6). NVSN estimates the incidence of pathogen-specific pediatric ARIs and collects clinical data (e.g., underlying medical conditions and vaccination status) to assess risk factors for severe disease and calculate influenza and COVID-19 vaccine effectiveness. Current NVSN inpatient (i.e., hospital) surveillance began in 2015, expanded to emergency departments (EDs) in 2016, and to outpatient clinics in 2018. This report describes demographic characteristics of enrolled children who received care in these settings, and yearly circulation of influenza, RSV, HMPV, HPIV1-3, adenovirus, human rhinovirus and enterovirus (RV/EV),* and SARS-CoV-2 during December 2016-August 2021. Among 90,085 eligible infants, children, and adolescents (children) aged <18 years with ARI, 51,441 (57%) were enrolled, nearly 75% of whom were aged <5 years; 43% were hospitalized. Infants aged <1 year accounted for the largest proportion (38%) of those hospitalized. The most common pathogens detected were RV/EV and RSV. Before the emergence of SARS-CoV-2, detected respiratory viruses followed previously described seasonal trends, with annual peaks of influenza and RSV in late fall and winter (7,8). After the emergence of SARS-CoV-2 and implementation of associated pandemic nonpharmaceutical interventions and community mitigation measures, many respiratory viruses circulated at lower-than-expected levels during April 2020-May 2021. Beginning in summer 2021, NVSN detected higher than anticipated enrollment of hospitalized children as well as atypical interseasonal circulation of RSV. Further analyses of NVSN data and continued surveillance are vital in highlighting risk factors for severe disease and health disparities, measuring the effectiveness of vaccines and monoclonal antibody-based prophylactics, and guiding policies to protect young children from pathogens such as SARS-CoV-2, influenza, and RSV.
Topics: Adolescent; Antibodies, Monoclonal; COVID-19; COVID-19 Vaccines; Child; Child, Preschool; Humans; Infant; Influenza, Human; Metapneumovirus; Prospective Studies; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; SARS-CoV-2; United States; Viruses
PubMed: 36201373
DOI: 10.15585/mmwr.mm7140a1 -
International Journal of Environmental... Jan 2020Respiratory viruses are a common cause of respiratory tract infection (RTI), particularly in neonates and children. Rapid and accurate diagnosis of viral infections...
Respiratory viruses are a common cause of respiratory tract infection (RTI), particularly in neonates and children. Rapid and accurate diagnosis of viral infections could improve clinical outcomes and reduce the use of antibiotics and treatment sessions. Advances in diagnostic technology contribute to the accurate detection of viruses. We performed a multiplex real-time polymerase chain reaction (PCR) to investigate the viral etiology in pediatric patients and compared the detection rates with those determined using traditional antigen tests and virus cultures. Fifteen respiratory viruses were included in our investigation: respiratory syncytial virus A/B (RSV), influenza virus A (FluA) and influenza virus B (FluB), human metapneumovirus (MPV), enterovirus (EV), human parainfluenza virus (PIV) types 1-4, human rhinovirus (RV), human coronavirus OC43, NL63, and 229E, human adenovirus (ADV), and human bocavirus (Boca). In total, 474 specimens were collected and tested. Respiratory viruses were detected more frequently by PCR (357, 75.3%) than they were by traditional tests (229, 49.3%). The leading pathogens were RSV (113, 23.8%), RV (72, 15.2%), PIV3 (53, 11.2%), FluA (51, 10.8%), and ADV (48, 10.1%). For children younger than 5 years, RSV and RV were most prevalent; for children older than 5 years, FluA and ADV were the most frequently detected. Of the specimens, 25.8% (92/357) were coinfected with two or more viruses. RV, Boca, PIV2, FluB, and PIV4 had higher rates of coinfection; MPV and PIV1 had the lowest rates of coinfection (9.1% and 5.3%). To conclude, the detection power of PCR was better than that of traditional antigen tests and virus cultures when considering the detection of respiratory viruses. RSV and RV were the leading viral pathogens identified in the respiratory specimens. One-quarter of the positive specimens were coinfected with two or more viruses. In the future, further application of PCR may contribute to the rapid and accurate diagnosis of respiratory viruses and could improve patient outcomes.
Topics: Child; Child, Preschool; Coinfection; Female; Humans; Infant; Infant, Newborn; Male; Microbiological Techniques; Real-Time Polymerase Chain Reaction; Respiratory Tract Infections; Virus Diseases
PubMed: 31952364
DOI: 10.3390/ijerph17020564