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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 -
Intervirology 2017The families Paramyxoviridae and Pneumoviridae comprise a broad spectrum of viral pathogens that affect human health. The matrix (M) protein of these viruses has a...
BACKGROUND
The families Paramyxoviridae and Pneumoviridae comprise a broad spectrum of viral pathogens that affect human health. The matrix (M) protein of these viruses has a central role in their life cycle. In line with this, molecular characteristics of the M proteins from variable viruses that circulated in Croatia were investigated.
METHODS
Sequences of the M proteins of human parainfluenza virus (HPIV) 1-3 within the family Paramyxoviridae, human metapneumovirus (HMPV), and human respiratory syncytial virus from the family Pneumoviridae were obtained and analyzed.
RESULTS
M proteins were very diverse among HPIVs, but highly conserved within each virus. More variability was seen in nucleotide sequences of M proteins from the Pneumoviridae family. An insertion of 8 nucleotides in the 3' untranslated region in 1 HMPV M gene sequence was discovered (HR347-12). As there are no samples with such an insertion in the database, this insertion is of interest and requires further research.
CONCLUSION
While we have confirmed that M proteins were conserved among individual viruses, any changes that are observed should be given attention and further researched. Of special interest is inclusion of HPIV2 M proteins in this analysis, as these proteins have not been studied to the same extent as other paramyxoviruses.
Topics: Amino Acid Sequence; Animals; Chlorocebus aethiops; Gene Expression; Genetic Variation; High-Throughput Nucleotide Sequencing; Humans; Metapneumovirus; Parainfluenza Virus 1, Human; Paramyxoviridae Infections; RNA, Viral; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Respirovirus Infections; Sequence Alignment; Sequence Homology, Amino Acid; Vero Cells; Viral Matrix Proteins
PubMed: 29510403
DOI: 10.1159/000487049 -
Microbiology and Immunology 1982
Review
Topics: Capsid; Cell Membrane; Chemical Phenomena; Chemistry; Defective Viruses; Glycoproteins; Lipids; Newcastle disease virus; Parainfluenza Virus 1, Human; Paramyxoviridae; Phosphorylation; Respirovirus; Viral Matrix Proteins; Viral Proteins; Virion
PubMed: 6287180
DOI: 10.1111/j.1348-0421.1982.tb00180.x -
MBio May 2019Paramyxoviruses and pneumoviruses have similar life cycles and share the respiratory tract as a point of entry. In comparative genome-scale siRNA screens with... (Comparative Study)
Comparative Study
Paramyxoviruses and pneumoviruses have similar life cycles and share the respiratory tract as a point of entry. In comparative genome-scale siRNA screens with wild-type-derived measles, mumps, and respiratory syncytial viruses in A549 cells, a human lung adenocarcinoma cell line, we identified vesicular transport, RNA processing pathways, and translation as the top pathways required by all three viruses. As the top hit in the translation pathway, ABCE1, a member of the ATP-binding cassette transporters, was chosen for further study. We found that ABCE1 supports replication of all three viruses, confirming its importance for viruses of both families. More detailed characterization revealed that ABCE1 is specifically required for efficient viral but not general cellular protein synthesis, indicating that paramyxoviral and pneumoviral mRNAs exploit specific translation mechanisms. In addition to providing a novel overview of cellular proteins and pathways that impact these important pathogens, this study highlights the role of ABCE1 as a host factor required for efficient paramyxovirus and pneumovirus translation. The and families include important human and animal pathogens. To identify common host factors, we performed genome-scale siRNA screens with wild-type-derived measles, mumps, and respiratory syncytial viruses in the same cell line. A comparative bioinformatics analysis yielded different members of the coatomer complex I, translation factors ABCE1 and eIF3A, and several RNA binding proteins as cellular proteins with proviral activity for all three viruses. A more detailed characterization of ABCE1 revealed its essential role for viral protein synthesis. Taken together, these data sets provide new insight into the interactions between paramyxoviruses and pneumoviruses and host cell proteins and constitute a starting point for the development of broadly effective antivirals.
Topics: A549 Cells; ATP-Binding Cassette Transporters; Computational Biology; Gene Expression; Host Microbial Interactions; Humans; Paramyxoviridae; Pneumovirus; RNA, Messenger; RNA, Small Interfering; RNA-Binding Proteins
PubMed: 31088929
DOI: 10.1128/mBio.00826-19 -
Clinical Microbiology and Infection :... Apr 2006Acute respiratory tract infections (ARTIs) are a leading cause of morbidity and mortality in children worldwide, but the aetiology of many ARTIs is still unknown. In... (Review)
Review
Acute respiratory tract infections (ARTIs) are a leading cause of morbidity and mortality in children worldwide, but the aetiology of many ARTIs is still unknown. In 2001, researchers in The Netherlands reported the discovery of a previously unidentified pathogen called human metapneumovirus (hMPV). Since its initial description, hMPV has been associated with ARTI in Europe (Italy, France, Spain, the UK, Germany, Denmark, Finland and Norway), America (the USA, Canada, Argentina and Brazil), Asia (India, Japan, China and Singapore), Australia and South Africa in individuals of all ages. The incidence of infection varies from 1.5% to 25%, indicating that hMPV is a ubiquitous virus with a worldwide distribution. hMPV seems to play an important role as a cause of paediatric upper and lower respiratory tract infection, with similar, but not identical, epidemiological and clinical features to those of respiratory syncytial virus and influenza virus. Moreover, the socio-economic impact of hMPV-infected children on their families seems to be considerable, which suggests that, like influenza virus, hMPV infection may be a substantial public health problem for the community. It may be associated with significant morbidity and mortality in pre-term infants and children with underlying clinical conditions, although more adequately controlled studies are needed to confirm its importance in such patients. Many fundamental questions concerning the pathogenesis of hMPV disease and the host's specific immune response remain to be answered. Further studies are also required to properly define hMPV diagnosis, treatment and prevention strategies.
Topics: Animals; Child; Humans; Metapneumovirus; Paramyxoviridae Infections; Respiratory Tract Infections
PubMed: 16524405
DOI: 10.1111/j.1469-0691.2005.01325.x -
Virology Nov 2016The recent flurry of high resolution structures of Negative Strand RNA Virus RNA-dependent RNA polymerases has rekindled interest in the manner in which these... (Review)
Review
The recent flurry of high resolution structures of Negative Strand RNA Virus RNA-dependent RNA polymerases has rekindled interest in the manner in which these polymerases, and in particular those of the nonsegmented viruses, recognize the RNA sequences that control mRNA synthesis and genome replication. In the light of these polymerase structures, we re-examine some unusual aspects of the Paramyxoviridae, namely bipartite replication promoters and mRNA editing, and the manner in which these properties are governed by genome hexamer phase.
Topics: 3' Untranslated Regions; Animals; Gene Expression Regulation, Viral; Genome, Viral; Humans; Paramyxoviridae; Promoter Regions, Genetic; RNA Editing; RNA, Messenger; RNA, Viral; Transcription, Genetic; Viral Proteins
PubMed: 27567257
DOI: 10.1016/j.virol.2016.08.018 -
Clinical Features of Human Metapneumovirus-Associated Community-acquired Pneumonia Hospitalizations.Clinical Infectious Diseases : An... Jan 2021Human metapneumovirus (HMPV) is a leading cause of respiratory tract infections. Few studies have compared the clinical characteristics and severity of HMPV-associated...
BACKGROUND
Human metapneumovirus (HMPV) is a leading cause of respiratory tract infections. Few studies have compared the clinical characteristics and severity of HMPV-associated pneumonia with other pathogens.
METHODS
Active, population-based surveillance was previously conducted for radiographically confirmed, community-acquired pneumonia hospitalizations among children and adults in 8 United States hospitals. Clinical data and specimens for pathogen detection were systematically collected. We described clinical features of all HMPV-associated pneumonia and, after excluding codetections with other pathogen types, we compared features of HMPV-associated pneumonia with other viral, atypical, and bacterial pneumonia and modeled the severity (mild, moderate, and severe) and length of stay using multivariable proportional odds regression.
RESULTS
HMPV was detected in 298/2358 (12.6%) children and 88/2320 (3.8%) adults hospitalized with pneumonia and was commonly codetected with other pathogens (125/298 [42%] children and 21/88 [24%] adults). Fever and cough were the most common presenting symptoms of HMPV-associated pneumonia and were also common symptoms of other pathogens. After excluding codetections in children (n = 1778), compared to HMPV (reference), bacterial pneumonia exhibited increased severity (odds ratio [OR], 3.66; 95% confidence interval [CI], 1.43-9.40), respiratory syncytial virus (RSV; OR, 0.76; 95% CI, .59-.99) and atypical (OR, 0.39; 95% CI, .19-.81) infections exhibited decreased severity, and other viral pneumonia exhibited similar severity (OR, 0.88; 95% CI, .55-1.39). In adults (n = 2145), bacterial (OR, 3.74; 95% CI, 1.87-7.47) and RSV pneumonia (OR, 1.82; 95% CI, 1.32-2.50) were more severe than HMPV (reference), but all other pathogens had similar severity.
CONCLUSIONS
Clinical features did not reliably distinguish HMPV-associated pneumonia from other pathogens. HMPV-associated pneumonia was less severe than bacterial and adult RSV pneumonia, but was otherwise as or more severe than other common pathogens.
Topics: Adult; Child; Hospitalization; Humans; Infant; Metapneumovirus; Paramyxoviridae Infections; Pneumonia, Viral; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections
PubMed: 32010955
DOI: 10.1093/cid/ciaa088 -
Viruses Jun 2019Canine distemper virus (CDV) is a worldwide distributed virus which belongs to the genus within the family. CDV spreads through the lymphatic, epithelial, and nervous... (Review)
Review
Canine distemper virus (CDV) is a worldwide distributed virus which belongs to the genus within the family. CDV spreads through the lymphatic, epithelial, and nervous systems of domestic dogs and wildlife, in at least six orders and over 20 families of mammals. Due to the high morbidity and mortality rates and broad host range, understanding the epidemiology of CDV is not only important for its control in domestic animals, but also for the development of reliable wildlife conservation strategies. The present review aims to give an outlook of the multiple evolutionary landscapes and factors involved in the transmission of CDV by including epidemiological data from multiple species in urban, wild and peri-urban settings, not only in domestic animal populations but at the wildlife interface. It is clear that different epidemiological scenarios can lead to the presence of CDV in wildlife even in the absence of infection in domestic populations, highlighting the role of CDV in different domestic or wild species without clinical signs of disease mainly acting as reservoirs (peridomestic and mesocarnivores) that are often found in peridomestic habits triggering CDV epidemics. Another scenario is driven by mutations, which generate genetic variation on which random drift and natural selection can act, shaping the genetic structure of CDV populations leading to some fitness compensations between hosts and driving the evolution of specialist and generalist traits in CDV populations. In this scenario, the highly variable protein hemagglutinin (H) determines the cellular and host tropism by binding to signaling lymphocytic activation molecule (SLAM) and nectin-4 receptors of the host; however, the multiple evolutionary events that may have facilitated CDV adaptation to different hosts must be evaluated by complete genome sequencing. This review is focused on the study of CDV interspecies transmission by examining molecular and epidemiological reports based on sequences of the hemagglutinin gene and the growing body of studies of the complete genome; emphasizing the importance of long-term multidisciplinary research that tracks CDV in the presence or absence of clinical signs in wild species, and helping to implement strategies to mitigate the infection. Integrated research incorporating the experience of wildlife managers, behavioral and conservation biologists, veterinarians, virologists, and immunologists (among other scientific areas) and the inclusion of several wild and domestic species is essential for understanding the intricate epidemiological dynamics of CDV in its multiple host infections.
Topics: Animals; Animals, Wild; Distemper; Distemper Virus, Canine; Dogs; Evolution, Molecular; Host Specificity; Phylogeny
PubMed: 31247987
DOI: 10.3390/v11070582 -
Journal of Virology Aug 1997On the basis of the conservation of neuraminidase (N) active-site residues in influenza virus N and paramyxovirus hemagglutinin-neuraminidase (HN), it has been suggested...
On the basis of the conservation of neuraminidase (N) active-site residues in influenza virus N and paramyxovirus hemagglutinin-neuraminidase (HN), it has been suggested that the three-dimensional (3D) structures of the globular heads of the two proteins are broadly similar. In this study, details of this structural similarity are worked out. Detailed multiple sequence alignment of paramyxovirus HN proteins and influenza virus N proteins was based on the schematic representation of the previously proposed structural similarity. This multiple sequence alignment of paramyxovirus HN proteins was used as an intermediate to align the morbillivirus hemagglutinin (H) proteins with neuraminidase. Hypothetical 3D structures were built for paramyxovirus HN and morbillivirus H, based on homology modelling. The locations of insertions and deletions, glycosylation sites, active-site residues, and disulfide bridges agree with the proposed 3D structure of HN and H of the Paramyxoviridae. Moreover, details of the modelled H protein predict previously undescribed enzymatic activity. This prediction was confirmed for rinderpest virus and peste des petits ruminants virus. The enzymatic activity was highly substrate specific, because sialic acid was released only from crude mucins isolated from bovine submaxillary glands. The enzymatic activity may indicate a general infection mechanism for respiratory viruses, and the active site may prove to be a new target for antiviral compounds.
Topics: Amino Acid Sequence; Animals; Binding Sites; Chlorocebus aethiops; Disulfides; Epitopes; Glycosylation; HN Protein; Hemagglutinins, Viral; Molecular Sequence Data; Morbillivirus; Neuraminidase; Paramyxoviridae; Sequence Alignment; Substrate Specificity; Vero Cells
PubMed: 9223510
DOI: 10.1128/JVI.71.8.6155-6167.1997 -
Viruses Nov 2012The bovine respiratory syncytial virus (BRSV) is an enveloped, negative sense, single-stranded RNA virus belonging to the pneumovirus genus within the family... (Review)
Review
The bovine respiratory syncytial virus (BRSV) is an enveloped, negative sense, single-stranded RNA virus belonging to the pneumovirus genus within the family Paramyxoviridae. BRSV has been recognized as a major cause of respiratory disease in young calves since the early 1970s. The analysis of BRSV infection was originally hampered by its characteristic lability and poor growth in vitro. However, the advent of numerous immunological and molecular methods has facilitated the study of BRSV enormously. The knowledge gained from these studies has also provided the opportunity to develop safe, stable, attenuated virus vaccine candidates. Nonetheless, many aspects of the epidemiology, molecular epidemiology and evolution of the virus are still not fully understood. The natural course of infection is rather complex and further complicates diagnosis, treatment and the implementation of preventive measures aimed to control the disease. Therefore, understanding the mechanisms by which BRSV is able to establish infection is needed to prevent viral and disease spread. This review discusses important information regarding the epidemiology and molecular epidemiology of BRSV worldwide, and it highlights the importance of viral evolution in virus transmission.
Topics: Animals; Cattle; Cattle Diseases; Molecular Epidemiology; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Bovine
PubMed: 23202546
DOI: 10.3390/v4123452