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The Journal of Biological Chemistry Feb 2020Research in the last decade has uncovered many new paramyxoviruses, airborne agents that cause epidemic diseases in animals including humans. Most paramyxoviruses enter... (Review)
Review
Research in the last decade has uncovered many new paramyxoviruses, airborne agents that cause epidemic diseases in animals including humans. Most paramyxoviruses enter epithelial cells of the airway using sialic acid as a receptor and cause only mild disease. However, others cross the epithelial barrier and cause more severe disease. For some of these viruses, the host receptors have been identified, and the mechanisms of cell entry have been elucidated. The tetrameric attachment proteins of paramyxoviruses have vastly different binding affinities for their cognate receptors, which they contact through different binding surfaces. Nevertheless, all input signals are converted to the same output: conformational changes that trigger refolding of trimeric fusion proteins and membrane fusion. Experiments with selectively receptor-blinded viruses inoculated into their natural hosts have provided insights into tropism, identifying the cells and tissues that support growth and revealing the mechanisms of pathogenesis. These analyses also shed light on diabolically elegant mechanisms used by morbilliviruses, including the measles virus, to promote massive amplification within the host, followed by efficient aerosolization and rapid spread through host populations. In another paradigm of receptor-facilitated severe disease, henipaviruses, including Nipah and Hendra viruses, use different members of one protein family to cause zoonoses. Specific properties of different paramyxoviruses, like neurotoxicity and immunosuppression, are now understood in the light of receptor specificity. We propose that research on the specific receptors for several newly identified members of the family that may not bind sialic acid is needed to anticipate their zoonotic potential and to generate effective vaccines and antiviral compounds.
Topics: Animals; Humans; Membrane Fusion; Paramyxoviridae; Receptors, Virus; Tropism; Virus Attachment; Virus Internalization; Zoonoses
PubMed: 31949044
DOI: 10.1074/jbc.REV119.009961 -
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 -
Viruses Mar 2021Human metapneumovirus (hMPV) is one of the main pathogens responsible for acute respiratory infections in children up to 5 years of age, contributing substantially to... (Review)
Review
Human metapneumovirus (hMPV) is one of the main pathogens responsible for acute respiratory infections in children up to 5 years of age, contributing substantially to health burden. The worldwide economic and social impact of this virus is significant and must be addressed. The structural components of hMPV (either proteins or genetic material) can be detected by several receptors expressed by host cells through the engagement of pattern recognition receptors. The recognition of the structural components of hMPV can promote the signaling of the immune response to clear the infection, leading to the activation of several pathways, such as those related to the interferon response. Even so, several intrinsic factors are capable of modulating the immune response or directly inhibiting the replication of hMPV. This article will discuss the current knowledge regarding the innate and adaptive immune response during hMPV infections. Accordingly, the host intrinsic components capable of modulating the immune response and the elements capable of restricting viral replication during hMPV infections will be examined.
Topics: Adaptive Immunity; Child, Preschool; Host Microbial Interactions; Humans; Immunity, Innate; Metapneumovirus; Paramyxoviridae Infections
PubMed: 33809875
DOI: 10.3390/v13030519 -
Influenza and Other Respiratory Viruses Jan 2022The hospitalized acute respiratory tract infection (HARTI) study used the Respiratory Intensity and Impact Questionnaire (RiiQ™) Symptom Scale, derived from FluiiQ™,...
Comparative assessment of reported symptoms of influenza, respiratory syncytial virus, and human metapneumovirus infection during hospitalization and post-discharge assessed by Respiratory Intensity and Impact Questionnaire.
BACKGROUND
The hospitalized acute respiratory tract infection (HARTI) study used the Respiratory Intensity and Impact Questionnaire (RiiQ™) Symptom Scale, derived from FluiiQ™, to assess and compare the burden of respiratory infection symptoms for patients with influenza, respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) infection, with or without core risk factors (CRF) (age ≥65; chronic heart, renal, obstructive pulmonary disease; asthma).
METHODS
This was a prospective cohort study in adult patients hospitalized with acute respiratory tract infection (40 centers, 12 countries) during two consecutive influenza/RSV/hMPV seasons (2017-2019). The RiiQ™ Symptom Scale and EuroQol 5-Dimensions 5-Levels (EQ-5D-5L) were assessed by interview at two timepoints during hospitalization and at 1, 2, and 3 months post-discharge.
RESULTS
Mean lower respiratory tract (LRT) symptom scores were higher for RSV and hMPV participants compared to influenza at 48 h after enrollment/early discharge (p = 0.001) and 3 months post-discharge (p = 0.007). This was driven by LRT symptoms, including shortness of breath (SOB) (p < 0.01) and wheezing (p < 0.01) during hospitalization, and SOB (p < 0.05) and cough (p < 0.05) post-discharge. Participants with CRF reported more moderate-to-severe SOB (p < 0.05) and wheezing (p < 0.05) compared to CRF(-) participants post-discharge. EQ-5D-5L scores were moderately associated with RiiQ™ LRT and systemic symptoms domains.
CONCLUSIONS
Results from the HARTI study suggest that in the study population, LRT symptoms were more severe for RSV and hMPV groups and for patients with CRF. RiiQ™ Symptom Scale scores shows a moderate association with EQ-5D-5L indicating that the RiiQ™ may provide useful insights and offer advantages over other measures for use in interventional RSV adult clinical studies.
Topics: Adult; Aftercare; Hospitalization; Humans; Infant; Influenza, Human; Metapneumovirus; Paramyxoviridae Infections; Patient Discharge; Prospective Studies; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory System; Respiratory Tract Infections; Surveys and Questionnaires
PubMed: 34472708
DOI: 10.1111/irv.12903 -
Archives of Virology May 2018A number of unassigned viruses in the family Paramyxoviridae need to be classified either as a new genus or placed into one of the seven genera currently recognized in...
A number of unassigned viruses in the family Paramyxoviridae need to be classified either as a new genus or placed into one of the seven genera currently recognized in this family. Furthermore, numerous new paramyxoviruses continue to be discovered. However, attempts at classification have highlighted the difficulties that arise by applying historic criteria or criteria based on sequence alone to the classification of the viruses in this family. While the recent taxonomic change that elevated the previous subfamily Pneumovirinae into a separate family Pneumoviridae is readily justified on the basis of RNA dependent -RNA polymerase (RdRp or L protein) sequence motifs, using RdRp sequence comparisons for assignment to lower level taxa raises problems that would require an overhaul of the current criteria for assignment into genera in the family Paramyxoviridae. Arbitrary cut off points to delineate genera and species would have to be set if classification was based on the amino acid sequence of the RdRp alone or on pairwise analysis of sequence complementarity (PASC) of all open reading frames (ORFs). While these cut-offs cannot be made consistent with the current classification in this family, resorting to genus-level demarcation criteria with additional input from the biological context may afford a way forward. Such criteria would reflect the increasingly dynamic nature of virus taxonomy even if it would require a complete revision of the current classification.
Topics: Genome, Viral; Open Reading Frames; Paramyxoviridae; Phylogeny; RNA-Dependent RNA Polymerase
PubMed: 29372404
DOI: 10.1007/s00705-018-3720-2 -
Journal of Virology Aug 2020Wild birds are major natural reservoirs and potential dispersers of a variety of infectious diseases. As such, it is important to determine the diversity of viruses they...
Wild birds are major natural reservoirs and potential dispersers of a variety of infectious diseases. As such, it is important to determine the diversity of viruses they carry and use this information to help understand the potential risks of spillover to humans, domestic animals, and other wildlife. We investigated the potential viral causes of paresis in long-standing, but undiagnosed, disease syndromes in wild Australian birds. RNA from diseased birds was extracted and pooled based on tissue type, host species, and clinical manifestation for metagenomic sequencing. Using a bulk and unbiased metatranscriptomic approach, combined with clinical investigation and histopathology, we identified a number of novel viruses from the families , and in common urban wild birds, including Australian magpies, magpie larks, pied currawongs, Australian ravens, and rainbow lorikeets. In each case, the presence of the virus was confirmed by reverse transcription (RT)-PCR. These data revealed a number of candidate viral pathogens that may contribute to coronary, skeletal muscle, vascular, and neuropathology in birds of the and families and neuropathology in members of the The existence of such a diverse virome in urban avian species highlights the importance and challenges in elucidating the etiology and ecology of wildlife pathogens in urban environments. This information will be increasingly important for managing disease risks and conducting surveillance for potential viral threats to wildlife, livestock, and human health. Wildlife naturally harbor a diverse array of infectious microorganisms and can be a source of novel diseases in domestic animals and human populations. Using unbiased RNA sequencing, we identified highly diverse viruses in native birds from Australian urban environments presenting with paresis. This research included the clinical investigation and description of poorly understood recurring syndromes of unknown etiology: clenched claw syndrome and black and white bird disease. As well as identifying a range of potentially disease-causing viral pathogens, this study describes methods that can effectively and efficiently characterize emergent disease syndromes in free-ranging wildlife and promotes further surveillance for specific pathogens of potential conservation and zoonotic concern.
Topics: Adenoviridae; Animals; Animals, Wild; Astroviridae; Australia; Bird Diseases; Birds; Circoviridae; Cities; DNA Virus Infections; High-Throughput Nucleotide Sequencing; Humans; Metagenome; Paramyxoviridae; Parvoviridae; Phylogeny; Picornaviridae; Polyomaviridae; RNA Virus Infections; Transcriptome
PubMed: 32581107
DOI: 10.1128/JVI.00606-20 -
Viruses Sep 2022The viral genus includes two highly virulent zoonotic viruses of serious public health concern. and outbreaks are restricted to Australia and Southeast Asia,...
The viral genus includes two highly virulent zoonotic viruses of serious public health concern. and outbreaks are restricted to Australia and Southeast Asia, respectively. The Henipavirus genus comprises mostly bat-borne viruses, but exceptions have already been described as novel viruses with rodents and shrews as reservoir animals. In the Americas, scarce evidence supports the circulation of these viruses. In this communication, we report a novel henipa-like virus from opossums () from a forest fragment area in the Peixe-Boi municipality, Brazil, after which the virus was named the Peixe-Boi virus (PBV). The application of next-generation sequencing and metagenomic approach led us to discover the original evidence of a henipa-like virus genome in Brazil and South America and the original description of a henipa-like virus in marsupial species. These findings emphasize the importance of further studies to characterize PBV and clarify its ecology, impact on public health, and its relationship with didelphid marsupials and henipaviruses.
Topics: Animals; Henipavirus Infections; Brazil; Hendra Virus; Nipah Virus; Genomics; Chiroptera
PubMed: 36298723
DOI: 10.3390/v14102167 -
Proceedings. Biological Sciences Oct 2021Canine distemper virus (CDV) and phocine distemper virus (PDV) are major pathogens to terrestrial and marine mammals. Yet little is known about the timing and...
Canine distemper virus (CDV) and phocine distemper virus (PDV) are major pathogens to terrestrial and marine mammals. Yet little is known about the timing and geographical origin of distemper viruses and to what extent it was influenced by environmental change and human activities. To address this, we (i) performed the first comprehensive time-calibrated phylogenetic analysis of the two distemper viruses, (ii) mapped distemper antibody and virus detection data from marine mammals collected between 1972 and 2018, and (iii) compiled historical reports on distemper dating back to the eighteenth century. We find that CDV and PDV diverged in the early seventeenth century. Modern CDV strains last shared a common ancestor in the nineteenth century with a marked radiation during the 1930s-1950s. Modern PDV strains are of more recent origin, diverging in the 1970s-1980s. Based on the compiled information on distemper distribution, the diverse host range of CDV and basal phylogenetic placement of terrestrial morbilliviruses, we hypothesize a terrestrial CDV-like ancestor giving rise to PDV in the North Atlantic. Moreover, given the estimated timing of distemper origin and radiation, we hypothesize a prominent role of environmental change such as the Little Ice Age, and human activities like globalization and war in distemper virus evolution.
Topics: Animals; Cetacea; Distemper; Distemper Virus, Canine; Distemper Virus, Phocine; Dogs; Phylogeny
PubMed: 34702073
DOI: 10.1098/rspb.2021.1969 -
Journal of Virology Sep 2019We have developed a high-throughput sequencing (HTS) workflow for investigating paramyxovirus transcription and replication. We show that sequencing of...
We have developed a high-throughput sequencing (HTS) workflow for investigating paramyxovirus transcription and replication. We show that sequencing of oligo(dT)-selected polyadenylated mRNAs, without considering the orientation of the RNAs from which they had been generated, cannot accurately be used to analyze the abundance of viral mRNAs because genomic RNA copurifies with the viral mRNAs. The best method is directional sequencing of infected cell RNA that has physically been depleted of ribosomal and mitochondrial RNA followed by bioinformatic steps to differentiate data originating from genomes from viral mRNAs and antigenomes. This approach has the advantage that the abundance of viral mRNA (and antigenomes) and genomes can be analyzed and quantified from the same data. We investigated the kinetics of viral transcription and replication during infection of A549 cells with parainfluenza virus type 2 (PIV2), PIV3, PIV5, or mumps virus and determined the abundances of individual viral mRNAs and readthrough mRNAs. We found that the mRNA abundance gradients differed significantly between all four viruses but that for each virus the pattern remained relatively stable throughout infection. We suggest that rapid degradation of non-poly(A) mRNAs may be primarily responsible for the shape of the mRNA abundance gradient in parainfluenza virus 3, whereas a combination of this factor and disengagement of RNA polymerase at intergenic sequences, particularly those at the NP:P and P:M gene boundaries, may be responsible in the other viruses. High-throughput sequencing (HTS) of virus-infected cells can be used to study in great detail the patterns of virus transcription and replication. For paramyxoviruses, and by analogy for all other negative-strand RNA viruses, we show that directional sequencing must be used to distinguish between genomic RNA and mRNA/antigenomic RNA because significant amounts of genomic RNA copurify with poly(A)-selected mRNA. We found that the best method is directional sequencing of total cell RNA, after the physical removal of rRNA (and mitochondrial RNA), because quantitative information on the abundance of both genomic RNA and mRNA/antigenomes can be simultaneously derived. Using this approach, we revealed new details of the kinetics of virus transcription and replication for parainfluenza virus (PIV) type 2, PIV3, PIV5, and mumps virus, as well as on the relative abundance of the individual viral mRNAs.
Topics: A549 Cells; Gene Expression Profiling; Gene Expression Regulation, Viral; Genome Size; High-Throughput Nucleotide Sequencing; Humans; Paramyxoviridae Infections; Paramyxovirinae; RNA, Messenger; RNA, Viral; Species Specificity; Virus Replication; Whole Genome Sequencing
PubMed: 31189700
DOI: 10.1128/JVI.00571-19 -
Current Computer-aided Drug Design 2023Human parainfluenza viruses type 3 (HPIV-3) through bronchiolitis and pneumonia is a common cause of lower respiratory tract infections. It is the main cause of...
BACKGROUND
Human parainfluenza viruses type 3 (HPIV-3) through bronchiolitis and pneumonia is a common cause of lower respiratory tract infections. It is the main cause of hospitalization of infants and young children and also one of the main causes of morbidity and mortality in immuno-compromised and transplant patients. Despite many efforts, there is currently no specific anti-HPIV-3 drug or approved vaccine to prevent and control the virus. Identification of HPIV-3 epitopes with the capability of binding to human leukocyte antigen (HLA) class II molecules can be helpful in designing new vaccine candidates against HPIV-3 infection, and also can be useful for the in vitro stimulation and proliferation of HPIV-3-specific T cells for transplant and immunocompromised patients.
OBJECTIVE
To predict and comprehensively evaluate CD4T cell epitope (HLA-II binders) from four main HPIV-3 antigens.
METHODS
In the present work, we predicted and comprehensively evaluated CD4T cell epitope (HLA-II binders) from four main HPIV-3 antigens, including fusion protein (F), hemagglutininneuraminidase (HN), nucleocapsid (N) and matrix (M) proteins using bio- and immunoinformatics software. The toxicity, allergenicity, Blast screening and population coverage of the predicted epitopes were evaluated. The binding ability of the final selected epitopes was evaluated via a docking study.
RESULTS
After several filtering steps, including blast screening, toxicity and allergenicity assay, population coverage and docking study, 9 epitopes were selected as candidate epitopes. The selected epitopes showed high population coverage and docking studies revealed a significantly higher binding affinity for the final epitopes in comparison with the negative control peptides.
CONCLUSION
The final selected epitopes could be useful in designing vaccine candidates and for the treatment of immune-compromised individuals and patients with transplantation.
Topics: Child; Humans; Child, Preschool; Epitopes, T-Lymphocyte; Parainfluenza Virus 3, Human; HLA Antigens; Vaccines; CD4-Positive T-Lymphocytes; Paramyxoviridae Infections
PubMed: 36475332
DOI: 10.2174/1573409919666221205122633