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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 -
Nature Communications Apr 2012The large virus family Paramyxoviridae includes some of the most significant human and livestock viruses, such as measles-, distemper-, mumps-, parainfluenza-, Newcastle...
The large virus family Paramyxoviridae includes some of the most significant human and livestock viruses, such as measles-, distemper-, mumps-, parainfluenza-, Newcastle disease-, respiratory syncytial virus and metapneumoviruses. Here we identify an estimated 66 new paramyxoviruses in a worldwide sample of 119 bat and rodent species (9,278 individuals). Major discoveries include evidence of an origin of Hendra- and Nipah virus in Africa, identification of a bat virus conspecific with the human mumps virus, detection of close relatives of respiratory syncytial virus, mouse pneumonia- and canine distemper virus in bats, as well as direct evidence of Sendai virus in rodents. Phylogenetic reconstruction of host associations suggests a predominance of host switches from bats to other mammals and birds. Hypothesis tests in a maximum likelihood framework permit the phylogenetic placement of bats as tentative hosts at ancestral nodes to both the major Paramyxoviridae subfamilies (Paramyxovirinae and Pneumovirinae). Future attempts to predict the emergence of novel paramyxoviruses in humans and livestock will have to rely fundamentally on these data.
Topics: Animals; Chiroptera; Disease Reservoirs; Dogs; Humans; Mammals; Mice; Molecular Sequence Data; Paramyxoviridae; Paramyxoviridae Infections; Phylogeny
PubMed: 22531181
DOI: 10.1038/ncomms1796 -
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 -
The Journal of the American Board of... 2004Human metapneumovirus is an emerging human respiratory pathogen first discovered in 2001. It clinically resembles respiratory syncytial virus, can cause both upper and... (Review)
Review
Human metapneumovirus is an emerging human respiratory pathogen first discovered in 2001. It clinically resembles respiratory syncytial virus, can cause both upper and lower tract disease, and has been associated with serious illness in the young, among the immunosuppressed, and in the chronically ill. Cough and congestion are frequently reported, and respiratory failure may occur. Initial infection occurs during early childhood, and repeated infections throughout life impart only transient immunity. Diagnosis is by reverse transcription-polymerase chain reaction or rising serologic titers. No commercial laboratory tests or treatments are available. Primary care physicians should maintain vigilance for outbreaks of newly discovered and emerging respiratory illnesses.
Topics: Acute Disease; Communicable Diseases, Emerging; Humans; Metapneumovirus; Paramyxoviridae Infections; Respiratory Tract Infections
PubMed: 15575039
DOI: 10.3122/jabfm.17.6.466 -
Emerging Infectious Diseases Feb 2006We retrospectively studied 420 pharyngeal swab specimens collected from Peruvian and Argentinean patients with influenzalike illness in 2002 and 2003 for evidence of...
We retrospectively studied 420 pharyngeal swab specimens collected from Peruvian and Argentinean patients with influenzalike illness in 2002 and 2003 for evidence of human metapneumovirus (HMPV). Twelve specimens (2.3%) were positive by multiple assays. Six specimens yielded HMPV isolates. Four of the 6 isolates were of the uncommon B1 genotype.
Topics: Adolescent; Adult; Cell Line; Child; Child, Preschool; Female; Glycoproteins; Humans; Male; Metapneumovirus; Molecular Sequence Data; Paramyxoviridae Infections; Peru; Pharynx; Phylogeny; Population Surveillance; Sequence Analysis, DNA; Specimen Handling; Viral Proteins
PubMed: 16494771
DOI: 10.3201/eid1202.051133 -
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 -
Trends in Microbiology Jun 2006To deliver their genetic material into host cells, enveloped viruses have surface glycoproteins that actively cause the fusion of the viral and cellular membranes.... (Review)
Review
To deliver their genetic material into host cells, enveloped viruses have surface glycoproteins that actively cause the fusion of the viral and cellular membranes. Recently determined X-ray crystal structures of the paramyxovirus fusion (F) protein in its pre-fusion and post-fusion conformations reveal the dramatic structural transformation that this protein undergoes while causing membrane fusion. Conformational changes in key regions of the F protein suggest the mechanism by which the F protein is activated and refolds.
Topics: Membrane Fusion; Paramyxoviridae; Protein Conformation; Protein Structure, Tertiary; Viral Fusion Proteins
PubMed: 16678421
DOI: 10.1016/j.tim.2006.04.004 -
Neurotherapeutics : the Journal of the... Jul 2009Novel approaches to treatment of malignant glioma, the most frequently occurring primary brain tumor, have included the use of a wide range of oncolytic viral vectors.... (Review)
Review
Novel approaches to treatment of malignant glioma, the most frequently occurring primary brain tumor, have included the use of a wide range of oncolytic viral vectors. These vectors, either naturally tumor-selective, or engineered as such, have shown promise in the handful of phase I and phase II clinical trials conducted in recent years. The strategies developed for each of the different viruses currently being studied and the history of their development are summarized here. In addition, the results of clinical trials in patients and their implication for future trials are also discussed.
Topics: Adenoviridae; Animals; Brain Neoplasms; Clinical Trials as Topic; Genetic Vectors; Glioma; Herpesvirus 1, Human; Humans; Oncolytic Virotherapy; Oncolytic Viruses; Paramyxoviridae; Poliovirus; Poxviridae; Reoviridae; Rhabdoviridae
PubMed: 19560745
DOI: 10.1016/j.nurt.2009.04.011 -
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 -
Virology Jan 2006Measles virus belongs to the Paramyxoviridae family within the Mononegavirales order. Its non-segmented, single stranded, negative sense RNA genome is encapsidated by... (Review)
Review
Measles virus belongs to the Paramyxoviridae family within the Mononegavirales order. Its non-segmented, single stranded, negative sense RNA genome is encapsidated by the nucleoprotein (N) to form a helical nucleocapsid. This ribonucleoproteic complex is the substrate for both transcription and replication. The RNA-dependent RNA polymerase binds to the nucleocapsid template via its co-factor, the phosphoprotein (P). In this review, we summarize the main experimental data pointing out the abundance of structural disorder within measles virus N and P. We also describe studies indicating that structural disorder is a widespread property in the replicative complex of Paramyxoviridae and, more generally, of Mononegavirales. The functional implications of structural disorder are also discussed. Finally, we propose a model where the flexibility of the disordered N and P domains allows the formation of a tripartite complex (N degrees-P-L) during replication, followed by the delivery of N monomers to the newly synthesized genomic RNA chain.
Topics: Amino Acid Motifs; HSP72 Heat-Shock Proteins; Humans; Measles virus; Models, Molecular; Mononegavirales; Nucleocapsid; Nucleocapsid Proteins; Nucleoproteins; Paramyxovirinae; Phosphoproteins; Protein Binding; Species Specificity; Viral Proteins; Virus Replication
PubMed: 16364741
DOI: 10.1016/j.virol.2005.09.025