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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 -
The Lancet. Microbe Aug 2023
Topics: Humans; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections
PubMed: 37390835
DOI: 10.1016/S2666-5247(23)00195-7 -
Viruses May 2020Feline morbillivirus (FeMV) was first isolated in stray cats in Hong Kong in 2012. Since its discovery, the virus has been reported in domestic cats worldwide, including... (Review)
Review
Feline morbillivirus (FeMV) was first isolated in stray cats in Hong Kong in 2012. Since its discovery, the virus has been reported in domestic cats worldwide, including in Hong Kong, Japan, Italy, US, Brazil, Turkey, UK, Germany, and Malaysia. FeMV is classified in the genus within the family. FeMV research has focused primarily on determining the host range, symptoms, and characteristics of persistent infections in vitro. Importantly, there is a potential association between FeMV infection and feline kidney diseases, such as tubulointerstitial nephritis (TIN) and chronic kidney diseases (CKD), which are known to significantly affect feline health and survival. However, the tropism and viral entry mechanism(s) of FeMV remain unknown. In this review, we summarize the FeMV studies up to date, including the discoveries of various FeMV strains, basic virology, pathogenicity, and disease signs.
Topics: Animals; Cat Diseases; Cats; Kidney Diseases; Morbillivirus; Morbillivirus Infections; Paramyxoviridae
PubMed: 32370044
DOI: 10.3390/v12050501 -
MBio Jun 2022The Paramyxoviridae family comprises important pathogens that include measles (MeV), mumps, parainfluenza, and the emerging deadly zoonotic Nipah virus (NiV) and Hendra...
The Paramyxoviridae family comprises important pathogens that include measles (MeV), mumps, parainfluenza, and the emerging deadly zoonotic Nipah virus (NiV) and Hendra virus (HeV). Paramyxoviral entry into cells requires viral-cell membrane fusion, and formation of paramyxoviral pathognomonic syncytia requires cell-cell membrane fusion. Both events are coordinated by intricate interactions between the tetrameric attachment (G/H/HN) and trimeric fusion (F) glycoproteins. We report that receptor binding induces conformational changes in NiV G that expose its stalk domain, which triggers F through a cascade from prefusion to prehairpin intermediate (PHI) to postfusion conformations, executing membrane fusion. To decipher how the NiV G stalk may trigger F, we introduced cysteines along the G stalk to increase tetrameric strength and restrict stalk mobility. While most point mutants displayed near-wild-type levels of cell surface expression and receptor binding, most yielded increased NiV G oligomeric strength, and showed remarkably strong defects in syncytium formation. Furthermore, most of these mutants displayed stronger F/G interactions and significant defects in their ability to trigger F, indicating that NiV G stalk mobility is key to proper F triggering via moderate G/F interactions. Also remarkably, a mutant capable of triggering F and of fusion pore formation yielded little syncytium formation, implicating G or G/F interactions in a late step occurring post fusion pore formation, such as the extensive fusion pore expansion required for syncytium formation. This study uncovers novel mechanisms by which the G stalk and its oligomerization/mobility affect G/F interactions, the triggering of F, and a late fusion pore expansion step-exciting novel findings for paramyxoviral attachment glycoproteins. The important family includes measles, mumps, human parainfluenza, and the emerging deadly zoonotic Nipah virus (NiV) and Hendra virus (HeV). The deadly emerging NiV can cause neurologic and respiratory symptoms in humans with a >60% mortality rate. NiV has two surface proteins, the receptor binding protein (G) and fusion (F) glycoproteins. They mediate the required membrane fusion during viral entry into host cells and during syncytium formation, a hallmark of paramyxoviral and NiV infections. We previously discovered that the G stalk domain is important for triggering F (via largely unknown mechanisms) to induce membrane fusion. Here, we uncovered new roles and mechanisms by which the G stalk and its mobility modulate the triggering of F and also unexpectedly affect a very late step in membrane fusion, namely fusion pore expansion. Importantly, these novel findings may extend to other paramyxoviruses, offering new potential targets for therapeutic interventions.
Topics: Glycoproteins; Humans; Measles; Membrane Fusion; Mumps; Nipah Virus; Viral Envelope Proteins; Viral Fusion Proteins; Virus Attachment; Virus Internalization
PubMed: 35506666
DOI: 10.1128/mbio.03222-21 -
Virology Journal Mar 2024Human metapneumovirus (HMPV) is a newly identified pathogen causing acute respiratory tract infections in young infants worldwide. Since the initial document of HMPV... (Review)
Review
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.
Topics: Infant; Humans; Metapneumovirus; Paramyxoviridae Infections; Respiratory Tract Infections; Antiviral Agents; China; Vaccines
PubMed: 38454484
DOI: 10.1186/s12985-024-02327-9 -
Jornal de Pediatria 2023To identify and assess the current evidence available about the costs of managing hospitalized pediatric patients diagnosed with Respiratory Syncytial Virus (RSV) and... (Review)
Review
OBJECTIVE
To identify and assess the current evidence available about the costs of managing hospitalized pediatric patients diagnosed with Respiratory Syncytial Virus (RSV) and Parainfluenza Virus Type 3 (PIV3) in upper-middle-income countries.
METHODS
The authors conducted a systematic review across seven key databases from database inception to July 2022. Costs extracted were converted into 2022 International Dollars using the Purchasing Power Parity-adjusted. PROSPERO identifier: CRD42020225757.
RESULTS
No eligible study for PIV3 was recovered. For RSV, cost analysis and COI studies were performed for populations in Colombia, China, Malaysia, and Mexico. Comparing the total economic impact, the lowest cost per patient at the pediatric ward was observed in Malaysia ($ 347.60), while the highest was in Colombia ($ 709.66). On the other hand, at pediatric ICU, the lowest cost was observed in China ($ 1068.26), while the highest was in Mexico ($ 3815.56). Although there is no consensus on the major cost driver, all included studies described that the medications (treatment) consumed over 30% of the total cost. A high rate of inappropriate prescription drugs was observed.
CONCLUSION
The present study highlighted how RSV infection represents a substantial economic burden to health care systems and to society. The findings of the included studies suggest a possible association between baseline risk status and expenditures. Moreover, it was observed that an important amount of the cost is destinated to treatments that have no evidence or support in most clinical practice guidelines.
Topics: Humans; Child; Infant; Developing Countries; Financial Stress; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Parainfluenza Virus 3, Human; Hospitalization
PubMed: 37247828
DOI: 10.1016/j.jped.2023.05.003 -
International Journal of Infectious... Jul 2022To compare infection rates and circulating subtypes of human metapneumovirus (hMPV) before (2019-2020) and after the emergence of coronavirus disease 2019 (COVID-19)...
OBJECTIVES
To compare infection rates and circulating subtypes of human metapneumovirus (hMPV) before (2019-2020) and after the emergence of coronavirus disease 2019 (COVID-19) (2021) in Israel.
METHODS
In total, 12,718 respiratory samples were collected from hospitalized patients of all ages during the years 2019 to 2021 at the Sheba Medical Center in Israel and subjected to reverse transcription-polymerase chain reaction analysis. In addition, whole-genome sequencing was performed to characterize the subtypes of hMPV circulating in Israel between 2019 and 2021.
RESULTS
A total of 481 samples were found positive for hMPV. Before the emergence of COVID-19, hMPV peaked in winter months and declined thereafter. In sharp contrast, during the COVID-19 pandemic, we observed a delayed peak in hMPV infection cases and higher infection of young children. Viral sequencing showed a shift in the most prevalent circulating hMPV strain from A2b to B1 during the years 2019, 2020, and 2021.
CONCLUSION
Compared with the years before the COVID-19 pandemic, in 2021, hMPV mostly affected young children, and the most prevalent circulating subtype shifted from A2b in 2019 to B1.
Topics: COVID-19; Child; Child, Preschool; Genotype; Humans; Infant; Israel; Metapneumovirus; Pandemics; Paramyxoviridae Infections; Phylogeny; Prevalence; Respiratory Tract Infections
PubMed: 35472530
DOI: 10.1016/j.ijid.2022.04.037 -
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 -
Respirology (Carlton, Vic.) Nov 2021
Topics: Humans; Interleukin-17; Lung; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Virus Diseases
PubMed: 34580948
DOI: 10.1111/resp.14158 -
Journal of Virology Jun 2023Langya virus (LayV) is a paramyxovirus in the genus, closely related to the deadly Nipah (NiV) and Hendra (HeV) viruses, that was identified in August 2022 through...
Langya virus (LayV) is a paramyxovirus in the genus, closely related to the deadly Nipah (NiV) and Hendra (HeV) viruses, that was identified in August 2022 through disease surveillance following animal exposure in eastern China. Paramyxoviruses present two glycoproteins on their surface, known as attachment and fusion proteins, that mediate entry into cells and constitute the primary antigenic targets for immune response. Here, we determine cryo-electron microscopy (cryo-EM) structures of the uncleaved LayV fusion protein (F) ectodomain in pre- and postfusion conformations. The LayV-F protein exhibits pre- and postfusion architectures that, despite being highly conserved across paramyxoviruses, show differences in their surface properties, in particular at the apex of the prefusion trimer, that may contribute to antigenic variability. While dramatic conformational changes were visualized between the pre- and postfusion forms of the LayV-F protein, several domains remained invariant, held together by highly conserved disulfides. The LayV-F fusion peptide (FP) is buried within a highly conserved, hydrophobic interprotomer pocket in the prefusion state and is notably less flexible than the rest of the protein, highlighting its "spring-loaded" state and suggesting that the mechanism of pre-to-post transition must involve perturbations to the pocket and release of the fusion peptide. Together, these results offer a structural basis for how the Langya virus fusion protein compares to its Henipavirus relatives and propose a mechanism for the initial step of pre- to postfusion conversion that may apply more broadly to paramyxoviruses. The genus is quickly expanding into new animal hosts and geographic locations. This study compares the structure and antigenicity of the Langya virus fusion protein to other henipaviruses, which have important vaccine and therapeutic development implications. Furthermore, the study proposes a new mechanism to explain the early steps of the fusion initiation process that can be more broadly applied to the family.
Topics: Animals; Cryoelectron Microscopy; Henipavirus; Peptides; Protein Conformation; Viral Fusion Proteins; Virus Internalization
PubMed: 37278642
DOI: 10.1128/jvi.00433-23