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Epidemiology and Infection May 2023This study aims to evaluate the impact of non-pharmaceutical interventions (NPIs) on the prevalence of respiratory pathogens among hospitalised children with acute...
This study aims to evaluate the impact of non-pharmaceutical interventions (NPIs) on the prevalence of respiratory pathogens among hospitalised children with acute respiratory infections (ARIs) in Suzhou. Children with ARIs admitted to the Children's Hospital of Soochow University between 1 September 2021 and 31 December 2022 and subjected to 13 respiratory pathogen multiplex PCR assays were included in the study. We retrospectively collected demographic details, results of respiratory pathogen panel tests, and discharge diagnostic information of the participants, and described the age and seasonal distribution of respiratory pathogens and risk factors for developing pneumonia. A total of 10,396 children <16 years of age, including 5,905 males and 4,491 females, were part of the study. The positive rates of the 11 respiratory pathogen assays were 23.3% (human rhinovirus (HRV)), 15.9% (human respiratory syncytial virus (HRSV)), 10.5% (human metapneumovirus (HMPV)), 10.3% (human parainfluenza virus (HPIV)), 8.6% (mycoplasma pneumoniae (MP)), 5.8% (Boca), 3.5% (influenza A (InfA)), 2.9% (influenza B (InfB)), 2.7% (human coronavirus (HCOV)), 2.0% (adenovirus (ADV)), and 0.5% (Ch), respectively. Bocavirus and HPIV detection peaked during the period from September to November (autumn), and MP and HMPV peaked in the months of November and December. The peak of InfA detection was found to be in summer (July and August), whereas the InfB peak was observed to be in winter (December, January, and February). HRSV and HRV predominated in the <3 years age group. HRV and HMPV were common in the 3-6 years group, whereas MP was predominant in the ≥6 years group. MP (odds ratio (OR): 70.068, 95%CI: 32.665-150.298, < 0.01), HMPV (OR: 6.493, 95%CI: 4.802-8.780, < 0.01), Boca (OR: 3.300, 95%CI: 2.186-4.980, < 0.01), and HRSV (OR: 2.649, 95%CI: 2.089-3.358, < 0.01) infections were more likely to develop into pneumonia than the other pathogens. With the use of NPIs, HRV was the most common pathogen in children with ARIs, and MP was more likely to progress to pneumonia than other pathogens.
Topics: Child; Male; Female; Humans; Influenza, Human; Prevalence; Retrospective Studies; Pneumonia; Respiratory Tract Infections; Respiratory Syncytial Virus, Human; Metapneumovirus; China
PubMed: 37127406
DOI: 10.1017/S0950268823000626 -
Frontiers in Cell and Developmental... 2021N6-methyladenosine (mA) is a ubiquitous RNA modification in eukaryotes. It plays important roles in the translocation, stabilization and translation of mRNA. Many recent... (Review)
Review
N6-methyladenosine (mA) is a ubiquitous RNA modification in eukaryotes. It plays important roles in the translocation, stabilization and translation of mRNA. Many recent studies have shown that the dysregulation of mA modification is connected with diseases caused by pathogenic viruses, and studies on the role of mA in virus-host interactions have shown that mA plays a wide range of regulatory roles in the life cycle of viruses. Respiratory viruses are common pathogens that can impose a large disease burden on young children and elderly people. Here, we review the effects of mA modification on respiratory virus replication and life cycle and host immunity against viruses.
PubMed: 34368152
DOI: 10.3389/fcell.2021.699997 -
Microorganisms Jun 2021The human respiratory syncytial virus (hRSV) is one of the leading causes of acute lower respiratory tract infections in children under five years old. Notably, hRSV... (Review)
Review
The human respiratory syncytial virus (hRSV) is one of the leading causes of acute lower respiratory tract infections in children under five years old. Notably, hRSV infections can give way to pneumonia and predispose to other respiratory complications later in life, such as asthma. Even though the social and economic burden associated with hRSV infections is tremendous, there are no approved vaccines to date to prevent the disease caused by this pathogen. Recently, coinfections and superinfections have turned into an active field of study, and interactions between many viral and bacterial pathogens have been studied. hRSV is not an exception since polymicrobial infections involving this virus are common, especially when illness has evolved into pneumonia. Here, we review the epidemiology and recent findings regarding the main polymicrobial infections involving hRSV and several prevalent bacterial and viral respiratory pathogens, such as , , , , , , human rhinoviruses, influenza A virus, human metapneumovirus, and human parainfluenza viruses. As reports of most polymicrobial infections involving hRSV lack a molecular basis explaining the interaction between hRSV and these pathogens, we believe this review article can serve as a starting point to interesting and very much needed research in this area.
PubMed: 34199284
DOI: 10.3390/microorganisms9061293 -
PLoS Pathogens Sep 2023The Pneumoviridae family of viruses includes human metapneumovirus (HMPV) and respiratory syncytial virus (RSV). The closely related Paramyxoviridae family includes...
Structure-based design of a single-chain triple-disulfide-stabilized fusion-glycoprotein trimer that elicits high-titer neutralizing responses against human metapneumovirus.
The Pneumoviridae family of viruses includes human metapneumovirus (HMPV) and respiratory syncytial virus (RSV). The closely related Paramyxoviridae family includes parainfluenza viruses (PIVs). These three viral pathogens cause acute respiratory tract infections with substantial disease burden in the young, the elderly, and the immune-compromised. While promising subunit vaccines are being developed with prefusion-stabilized forms of the fusion glycoproteins (Fs) of RSV and PIVs, for which neutralizing titers elicited by the prefusion (pre-F) conformation of F are much higher than for the postfusion (post-F) conformation, with HMPV, pre-F and post-F immunogens described thus far elicit similar neutralizing responses, and it has been unclear which conformation, pre-F or post-F, would be the most effective HMPV F-vaccine immunogen. Here, we investigate the impact of further stabilizing HMPV F in the pre-F state. We replaced the furin-cleavage site with a flexible linker, creating a single chain F that yielded increased amounts of pre-F stabilized trimers, enabling the generation and assessment of F trimers stabilized by multiple disulfide bonds. Introduced prolines could increase both expression yields and antigenic recognition by the pre-F specific antibody, MPE8. The cryo-EM structure of a triple disulfide-stabilized pre-F trimer with the variable region of antibody MPE8 at 3.25-Å resolution confirmed the formation of designed disulfides and provided structural details on the MPE8 interface. Immunogenicity assessments in naïve mice showed the triple disulfide-stabilized pre-F trimer could elicit high titer neutralization, >10-fold higher than elicited by post-F. Immunogenicity assessments in pre-exposed rhesus macaques showed the triple disulfide-stabilized pre-F could recall high neutralizing titers after a single immunization, with little discrimination in the recall response between pre-F and post-F immunogens. However, the triple disulfide-stabilized pre-F adsorbed HMPV-directed responses from commercially available pooled human immunoglobulin more fully than post-F. Collectively, these results suggest single-chain triple disulfide-stabilized pre-F trimers to be promising HMPV-vaccine antigens.
Topics: Aged; Humans; Animals; Mice; Metapneumovirus; Macaca mulatta; Antibodies; Respiratory Syncytial Virus, Human; Antigens, Viral; Disulfides; Glycoproteins; Parainfluenza Virus 1, Human
PubMed: 37738240
DOI: 10.1371/journal.ppat.1011584 -
International Journal of Infectious... Dec 2023This study aimed to determine the epidemiological and genetic features of human metapneumovirus (HMPV) infection in children in southern China, and the effect of...
Epidemiology, genetic characteristics, and association with meteorological factors of human metapneumovirus infection in children in southern China: A 10-year retrospective study.
OBJECTIVES
This study aimed to determine the epidemiological and genetic features of human metapneumovirus (HMPV) infection in children in southern China, and the effect of meteorological factors on infection.
METHODS
14,817 children (≤14 years) with acute respiratory tract infections from 2010 to 2019 were examined for HMPV and other respiratory viruses by real-time quantitative polymerase chain reaction. Full-length F gene of 54 positive samples were sequenced and subjected to phylogenetic analysis. The correlation between the HMPV-positive rate and meteorological factors was analyzed by linear regression analysis.
RESULTS
HMPV was detected in 524 (3.5%) children, who were mostly younger than 1 year. The seasonal peak of HMPV prevalence mainly occurred in spring. Respiratory syncytial virus was the most common virus coinfected with HMPV (5.3%). Phylogenetic analysis revealed that the sequenced HMPV strains belonged to four sublineages, including A2b (1.9%), A2c (31.5%), B1 (50.0%), and B2 (16.7%). After adjusting for all meteorological factors, sunshine duration was inversely correlated with the HMPV-positive rate.
CONCLUSION
HMPV is an important respiratory pathogen that causes acute respiratory tract infections in children in southern China, particularly in children ≤5 years old. The prevalence peak of HMPV in this area appeared in spring, and the predominant subtype was B1. Meteorological factors, especially long sunshine duration, might decrease the HMPV prevalence.
Topics: Child; Humans; Infant; Child, Preschool; Metapneumovirus; Retrospective Studies; Molecular Epidemiology; Phylogeny; Paramyxoviridae Infections; Respiratory Tract Infections; China; Meteorological Concepts
PubMed: 37816430
DOI: 10.1016/j.ijid.2023.10.002 -
Viruses Dec 2021Pneumoviruses include pathogenic human and animal viruses, the most known and studied being the human respiratory syncytial virus (hRSV) and the metapneumovirus (hMPV),... (Review)
Review
Pneumoviruses include pathogenic human and animal viruses, the most known and studied being the human respiratory syncytial virus (hRSV) and the metapneumovirus (hMPV), which are the major cause of severe acute respiratory tract illness in young children worldwide, and main pathogens infecting elderly and immune-compromised people. The transcription and replication of these viruses take place in specific cytoplasmic inclusions called inclusion bodies (IBs). These activities depend on viral polymerase L, associated with its cofactor phosphoprotein P, for the recognition of the viral RNA genome encapsidated by the nucleoprotein N, forming the nucleocapsid (NC). The polymerase activities rely on diverse transient protein-protein interactions orchestrated by P playing the hub role. Among these interactions, P interacts with the NC to recruit L to the genome. The P protein also plays the role of chaperone to maintain the neosynthesized N monomeric and RNA-free (called N) before specific encapsidation of the viral genome and antigenome. This review aims at giving an overview of recent structural information obtained for hRSV and hMPV P, N, and more specifically for P-NC and N-P complexes that pave the way for the rational design of new antivirals against those viruses.
Topics: Animals; Antiviral Agents; Drug Design; Humans; Metapneumovirus; Models, Molecular; Nucleocapsid Proteins; Paramyxoviridae Infections; Phosphoproteins; Protein Binding; Protein Conformation; RNA, Viral; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Transcription, Genetic; Viral Proteins; Virus Replication
PubMed: 34960719
DOI: 10.3390/v13122449 -
Viral Immunology 2021The resolution revolution of cryo-electron microscopy (cryo-EM) has made a significant impact on the structural analysis of the multifunctional RNA polymerases. In...
The resolution revolution of cryo-electron microscopy (cryo-EM) has made a significant impact on the structural analysis of the multifunctional RNA polymerases. In recent months, several high-resolution structures of RNA polymerases of , which includes the human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV), have been determined by single-particle cryo-EM. These structures illustrated high similarities and minor differences between the polymerases and revealed the potential mechanisms of the RNA synthesis.
Topics: Cryoelectron Microscopy; DNA-Directed RNA Polymerases; Humans; Pneumovirus; Respiratory Syncytial Virus, Human
PubMed: 32429800
DOI: 10.1089/vim.2020.0018 -
Transplant Infectious Disease : An... Nov 2023Before the COVID-19 pandemic, common community-acquired seasonal respiratory viruses (CARVs) were a significant threat to the health and well-being of allogeneic... (Review)
Review
Before the COVID-19 pandemic, common community-acquired seasonal respiratory viruses (CARVs) were a significant threat to the health and well-being of allogeneic hematopoietic cell transplant (allo-HCT) recipients, often resulting in severe illness and even death. The pandemic has further highlighted the significant risk that immunosuppressed patients, including allo-HCT recipients, face when infected with SARS-CoV-2. As preventive transmission measures are relaxed and CARVs circulate again among the community, including in allo-HSCT recipients, it is crucial to understand the current state of knowledge, gaps, and recent advances regarding CARV infection in allo-HCT recipients. Urgent research is needed to identify seasonal respiratory viruses as potential drivers for future pandemics.
Topics: Humans; Respiratory Tract Infections; Hematopoietic Stem Cell Transplantation; Pandemics; Viruses; COVID-19
PubMed: 37585370
DOI: 10.1111/tid.14117 -
Virus Research Oct 2023Human metapneumovirus (HMPV) causes respiratory tract infections among infant, elderly, and immunocompromised patients, with significant mortality. Currently no licensed...
BACKGROUND
Human metapneumovirus (HMPV) causes respiratory tract infections among infant, elderly, and immunocompromised patients, with significant mortality. Currently no licensed vaccines or therapeutic agents of HMPV exist.
METHODS
HMPV virus-like particle (VLP) was constructed by co-expressing fusion protein of HMPV and matrix 1 protein of influenza virus using the baculovirus expression. Mice were immunized with VLP with or without aluminum hydroxide (alum) adjuvant by intramuscular route respectively. Sera were determined for titers of IgG and neutralizing antibody. Splenic lymphocytes were determined by IFN-γ and IL-4 ELISPOT. Mice were challenged with HMPV, and protective efficacy was evaluated.
RESULTS
We generated HMPV VLP in baculovirus expression system. After three times immunization, IgG antibody titers induced by VLP formulated with or without alum adjuvant group were 273,066 ± 100,331 and 136,533 ± 47,269 respectively, there was no difference (p ˃ 0.05); the neutralizing antibody titers vaccinated with VLP plus with alum adjuvant (266 ± 92) were higher than those of the VLP alone group (106 ± 37). For IFN-γ, mice vaccinated with VLP with or without alum adjuvant are 151 ± 36.4 and 77.0 ± 17.1SFC/10 respectively, there was difference (p = 0.03); For IL-4, they are 261.3 ± 38.7 versus 125.67 ± 29.78SFC/10 respectively, the difference was significant (p = 0.009). After challenge, in pathological analysis, the overall lesion scores in the VLP plus with and without alum adjuvant were 3.25 and 5.6 respectively, those of control group is 8. For immunohistochemical analyses, the average optical density of the lungs in the VLP immunized group containing adjuvant (9.07 ± 1.74) was lower than that in the VLP group without adjuvant (12.83 ± 2.31, p = 0.14).
CONCLUSIONS
This is the first study to demonstrate that HMPV VLP was successfully prepared in the baculovirus expression system. HMPV VLP could induce specific humoral and cellular immune responses as well as protective efficacy, and aluminum hydroxide may be an effective adjuvant in mice.
Topics: Humans; Mice; Animals; Aged; Metapneumovirus; Antibodies, Viral; Aluminum Hydroxide; Baculoviridae; Interleukin-4; Antibodies, Neutralizing; Adjuvants, Immunologic; Vaccines, Virus-Like Particle; Mice, Inbred BALB C
PubMed: 37657510
DOI: 10.1016/j.virusres.2023.199215 -
Communications Biology Jun 2023Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are related RNA viruses responsible for severe respiratory infections and resulting disease in...
Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are related RNA viruses responsible for severe respiratory infections and resulting disease in infants, elderly, and immunocompromised adults. Therapeutic small molecule inhibitors that bind to the RSV polymerase and inhibit viral replication are being developed, but their binding sites and molecular mechanisms of action remain largely unknown. Here we report a conserved allosteric inhibitory site identified on the L polymerase proteins of RSV and HMPV that can be targeted by a dual-specificity, non-nucleoside inhibitor, termed MRK-1. Cryo-EM structures of the inhibitor in complexes with truncated RSV and full-length HMPV polymerase proteins provide a structural understanding of how MRK-1 is active against both viruses. Functional analyses indicate that MRK-1 inhibits conformational changes necessary for the polymerase to engage in RNA synthesis initiation and to transition into an elongation mode. Competition studies reveal that the MRK-1 binding pocket is distinct from that of a capping inhibitor with an overlapping resistance profile, suggesting that the polymerase conformation bound by MRK-1 may be distinct from that involved in mRNA capping. These findings should facilitate optimization of dual RSV and HMPV replication inhibitors and provide insights into the molecular mechanisms underlying their polymerase activities.
Topics: Infant; Adult; Humans; Aged; Metapneumovirus; RNA-Dependent RNA Polymerase; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; RNA, Messenger
PubMed: 37337079
DOI: 10.1038/s42003-023-04990-0