-
MBio Feb 2023Human metapneumovirus (HMPV) is one of the leading causes of respiratory illness (RI), primarily in infants. Worldwide, two genetic lineages (A and B) of HMPV are...
Human metapneumovirus (HMPV) is one of the leading causes of respiratory illness (RI), primarily in infants. Worldwide, two genetic lineages (A and B) of HMPV are circulating that are antigenically distinct and can each be further divided into genetic sublineages. Surveillance combined with large-scale whole-genome sequencing studies of HMPV are scarce but would help to identify viral evolutionary dynamics. Here, we analyzed 130 whole HMPV genome sequences obtained from samples collected from individuals hospitalized with RI and partial fusion ( = 144) and attachment ( = 123) protein gene sequences obtained from samples collected from patients with RI visiting general practitioners between 2005 and 2021 in the Netherlands. Phylogenetic analyses demonstrated that HMPV continued to group in the four sublineages described in 2004 (A1, A2, B1, and B2). However, one sublineage (A1) was no longer detected in the Netherlands after 2006, while the others continued to evolve. No differences were observed in dominant (sub)lineages between samples obtained from patients with RI being hospitalized and those consulting general practitioners. In both populations, viruses of lineage A2 carrying a 180-nucleotide or 111-nucleotide duplication in the attachment protein gene became the most frequently detected genotypes. In the past, different names for the newly energing lineages have been proposed, demonstrating the need for a consistent naming convention. Here, criteria are proposed for the designation of new genetic lineages to aid in moving toward a systematic HMPV classification. Human metapneumovirus (HMPV) is one of the major causative agents of human respiratory tract infections. Monitoring of virus evolution could aid toward the development of new antiviral treatments or vaccine designs. Here, we studied HMPV evolution between 2005 and 2021, with viruses obtained from samples collected from hospitalized individuals and patients with respiratory infections consulting general practitioners. Phylogenetic analyses demonstrated that HMPV continued to group in the four previously described sublineages (A1, A2, B1, and B2). However, one sublineage (A1) was no longer detected after 2006, while the others continued to evolve. No differences were observed in dominant (sub)lineages between patients being hospitalized and those consulting general practitioners. In both populations, viruses of lineage A2 carrying a 180-nucleotide or 111-nucleotide duplication in the attachment protein gene became the most frequently detected genotypes. These data were used to propose criteria for the designation of new genetic lineages to aid toward a systematic HMPV classification.
Topics: Infant; Humans; Metapneumovirus; Paramyxoviridae Infections; Phylogeny; Genetic Variation; Respiratory Tract Infections; Genotype; Nucleotides
PubMed: 36507832
DOI: 10.1128/mbio.02280-22 -
Virus Genes Aug 2023Human metapneumovirus (HMPV) is a major pathogen of acute respiratory tract infections (ARTIs) in children. Whole genome sequence analyses could help understand the...
Human metapneumovirus (HMPV) is a major pathogen of acute respiratory tract infections (ARTIs) in children. Whole genome sequence analyses could help understand the evolution and transmission events of this virus. In this study, we sequenced HMPV whole genomes to improve the identification of molecular epidemiology in Beijing, China. Nasopharyngeal aspirates of hospitalized children aged < 14 years old with ARTIs were screened for HMPV infection using qPCR. Fourteen pairs of overlapping primers were used to amplify whole genome sequences of HMPV from positive samples with high viral loads. The epidemiology of HMPV was analysed and 27 HMPV whole genome sequences were obtained. Sequence identity and the positional entropy analyses showed that most regions of HMPV genome are conserved, whereas the G gene contained many variations. Phylogenetic analysis identified 25 HMPV sequences that belonged to a newly defined subtype A2b1; G gene sequences from 24 of these contained a 111-nucleotide duplication. HMPV is an important respiratory pathogen in paediatric patients. The new subtype A2b1 with a 111-nucleotide duplication has become predominate in Beijing, China.
Topics: Whole Genome Sequencing; Metapneumovirus; Evolution, Molecular; Humans; Male; Female; Infant; Child, Preschool; Child; Adolescent; Paramyxoviridae Infections; Phylogeny
PubMed: 37150780
DOI: 10.1007/s11262-023-02001-2 -
The Journal of General Virology Jul 2015Human metapneumovirus (hMPV) and respiratory syncytial virus, its close family member, are two major causes of lower respiratory tract infection in the paediatric... (Review)
Review
Human metapneumovirus (hMPV) and respiratory syncytial virus, its close family member, are two major causes of lower respiratory tract infection in the paediatric population. hMPV is also a common cause of worldwide morbidity and mortality in immunocompromised patients and older adults. Repeated infections occur often, demonstrating a heavy medical burden. However, there is currently no hMPV-specific prevention treatment. This review focuses on the current literature on hMPV vaccine development. We believe that a better understanding of the role(s) of viral proteins in host responses might lead to efficient prophylactic vaccine development.
Topics: Drug Discovery; Host-Pathogen Interactions; Humans; Metapneumovirus; Paramyxoviridae Infections; Vaccination; Viral Proteins; Viral Vaccines
PubMed: 25667325
DOI: 10.1099/vir.0.000083 -
Viruses Sep 2018Human metapneumovirus (HMPV) is one of the leading causes of respiratory diseases in infants and children worldwide. Although this pathogen infects mainly young... (Review)
Review
Human metapneumovirus (HMPV) is one of the leading causes of respiratory diseases in infants and children worldwide. Although this pathogen infects mainly young children, elderly and immunocompromised people can be also seriously affected. To date, there is no commercial vaccine available against it. Upon HMPV infection, the host innate arm of defense produces interferons (IFNs), which are critical for limiting HMPV replication. In this review, we offer an updated landscape of the HMPV mediated-IFN response in different models as well as some of the defense tactics employed by the virus to circumvent IFN response.
Topics: Animals; Disease Models, Animal; Gene Expression Regulation, Viral; Genome, Viral; Genomics; Host-Pathogen Interactions; Humans; Interferons; Metapneumovirus; Paramyxoviridae Infections; Virus Replication
PubMed: 30231515
DOI: 10.3390/v10090505 -
Pathologie-biologie Mar 2009The human metapneumovirus (hMPV) is a new Pneumovirinae related to the avian metapneumovirus type C. hMPV genome differs from human respiratory syncytial virus (RSV)... (Review)
Review
The human metapneumovirus (hMPV) is a new Pneumovirinae related to the avian metapneumovirus type C. hMPV genome differs from human respiratory syncytial virus (RSV) genome by the gene order and the lack of nonstructural genes. Two genetic sub-groups and four sub-types of hMPV are identified. hMPV infections evolve as regular winter outbreaks which have roughly the same size and overlaping RSV epidemics. Among hospitalized children in Caen, hMPV is detected in 9.7% of the cases after RSV (37%), rhinovirus (18%), influenza virus (14.5%), adenovirus (9%), and parainfluenza virus (5%). Most of hMPV infections are observed in children suffering from bronchiolitis, but the localization to lower respiratory tract and the severity of the disease are less frequent in comparison with RSV infections. hMPV is very difficult to isolate using cell culture. Up to now, the only way for hMPV diagnosis was the TS-CRP assays. But the recent apparition of direct antigenic tests allows us to get a fair, rapid, and economic diagnostic tool.
Topics: Child; Diagnosis, Differential; Disease Outbreaks; France; Genome, Viral; Humans; Influenza, Human; Metapneumovirus; Orthomyxoviridae; Paramyxoviridae Infections; Phylogeny; Retroviridae Infections; Rous sarcoma virus
PubMed: 18515017
DOI: 10.1016/j.patbio.2008.04.005 -
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 -
Viruses Jan 2013Human metapneumovirus (HMPV) is a leading cause of respiratory infection that causes upper airway and severe lower respiratory tract infections. HMPV infection is... (Review)
Review
Human metapneumovirus (HMPV) is a leading cause of respiratory infection that causes upper airway and severe lower respiratory tract infections. HMPV infection is initiated by viral surface glycoproteins that attach to cellular receptors and mediate virus membrane fusion with cellular membranes. Most paramyxoviruses use two viral glycoproteins to facilitate virus entry-an attachment protein and a fusion (F) protein. However, membrane fusion for the human paramyxoviruses in the Pneumovirus subfamily, HMPV and respiratory syncytial virus (hRSV), is unique in that the F protein drives fusion in the absence of a separate viral attachment protein. Thus, pneumovirus F proteins can perform the necessary functions for virus entry, i.e., attachment and fusion. In this review, we discuss recent advances in the understanding of how HMPV F mediates both attachment and fusion. We review the requirements for HMPV viral surface glycoproteins during entry and infection, and review the identification of cellular receptors for HMPV F. We also review our current understanding of how HMPV F mediates fusion, concentrating on structural regions of the protein that appear to be critical for membrane fusion activity. Finally, we illuminate key unanswered questions and suggest how further studies can elucidate how this clinically important paramyxovirus fusion protein may have evolved to initiate infection by a unique mechanism.
Topics: Animals; Humans; Metapneumovirus; Paramyxoviridae Infections; Virus Internalization
PubMed: 23325326
DOI: 10.3390/v5010192 -
Viruses Jan 2013Human metapneumovirus (HMPV) is a relative newly described virus. It was first isolated in 2001 and currently appears to be one of the most significant and common human... (Review)
Review
Human metapneumovirus (HMPV) is a relative newly described virus. It was first isolated in 2001 and currently appears to be one of the most significant and common human viral infections. Retrospective serologic studies demonstrated the presence of HMPV antibodies in humans more than 50 years earlier. Although the virus was primarily known as causative agent of respiratory tract infections in children, HMPV is an important cause of respiratory infections in adults as well. Almost all children are infected by HMPV below the age of five; the repeated infections throughout life indicate transient immunity. HMPV infections usually are mild and self-limiting, but in the frail elderly and the immunocompromised patients, the clinical course can be complicated. Since culturing the virus is relatively difficult, diagnosis is mostly based on a nucleic acid amplification test, such as reverse transcriptase polymerase chain reaction. To date, no vaccine is available and treatment is supportive. However, ongoing research shows encouraging results. The aim of this paper is to review the current literature concerning HMPV infections in adults, and discuss recent development in treatment and vaccination.
Topics: Adult; Animals; Humans; Metapneumovirus; Paramyxoviridae Infections; Respiratory Tract Infections
PubMed: 23299785
DOI: 10.3390/v5010087 -
Viruses Mar 2022Metapneumoviruses, members of the family Pneumoviridae, have been identified in birds (avian metapneumoviruses; AMPV's) and humans (human metapneumoviruses; HMPV's).... (Review)
Review
Metapneumoviruses, members of the family Pneumoviridae, have been identified in birds (avian metapneumoviruses; AMPV's) and humans (human metapneumoviruses; HMPV's). AMPV and HMPV are closely related viruses with a similar genomic organization and cause respiratory tract illnesses in birds and humans, respectively. AMPV can be classified into four subgroups, A-D, and is the etiological agent of turkey rhinotracheitis and swollen head syndrome in chickens. Epidemiological studies have indicated that AMPV also circulates in wild bird species which may act as reservoir hosts for novel subtypes. HMPV was first discovered in 2001, but retrospective studies have shown that HMPV has been circulating in humans for at least 50 years. AMPV subgroup C is more closely related to HMPV than to any other AMPV subgroup, suggesting that HMPV has evolved from AMPV-C following zoonotic transfer. In this review, we present a historical perspective on the discovery of metapneumoviruses and discuss the host tropism, pathogenicity, and molecular characteristics of the different AMPV and HMPV subgroups to provide increased focus on the necessity to better understand the evolutionary pathways through which HMPV emerged as a seasonal endemic human respiratory virus.
Topics: Animals; Chickens; Humans; Metapneumovirus; Paramyxoviridae Infections; Poultry Diseases; Retrospective Studies
PubMed: 35458407
DOI: 10.3390/v14040677 -
Cell Reports Sep 2022Human metapneumovirus (hMPV) is a major cause of acute respiratory infections in infants and older adults, for which no vaccines or therapeutics are available. The viral...
Human metapneumovirus (hMPV) is a major cause of acute respiratory infections in infants and older adults, for which no vaccines or therapeutics are available. The viral fusion (F) glycoprotein is required for entry and is the primary target of neutralizing antibodies; however, little is known about the humoral immune response generated from natural infection. Here, using prefusion-stabilized F proteins to interrogate memory B cells from two older adults, we obtain over 700 paired non-IgM antibody sequences representing 563 clonotypes, indicative of a highly polyclonal response. Characterization of 136 monoclonal antibodies reveals broad recognition of the protein surface, with potently neutralizing antibodies targeting each antigenic site. Cryo-EM studies further reveal two non-canonical sites and the molecular basis for recognition of the apex of hMPV F by two prefusion-specific neutralizing antibodies. Collectively, these results provide insight into the humoral response to hMPV infection in older adults and will help guide vaccine development.
Topics: Aged; Antibodies, Monoclonal; Antibodies, Neutralizing; Antibodies, Viral; Humans; Metapneumovirus; Viral Fusion Proteins
PubMed: 36130517
DOI: 10.1016/j.celrep.2022.111399