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Viruses May 2022Newly emerging and seasonal respiratory viruses have a great impact on public health[...]
Newly emerging and seasonal respiratory viruses have a great impact on public health[...]
Topics: COVID-19; Humans; Influenza, Human; Membrane Glycoproteins; Orthomyxoviridae; Parainfluenza Virus 1, Human; Paramyxoviridae Infections; SARS-CoV-2; Vaccines
PubMed: 35746631
DOI: 10.3390/v14061160 -
Emerging Infectious Diseases Apr 2023We describe an unusual outbreak of respiratory infections caused by human metapneumovirus in children during the sixth wave of COVID-19 in Spain, associated with the...
We describe an unusual outbreak of respiratory infections caused by human metapneumovirus in children during the sixth wave of COVID-19 in Spain, associated with the Omicron variant. Patients in this outbreak were older than usual and showed more hypoxia and pneumonia, longer length of stay, and greater need for intensive care.
Topics: Child; Humans; COVID-19; Metapneumovirus; SARS-CoV-2; Spain; Pandemics; Paramyxoviridae Infections; Respiratory Tract Infections
PubMed: 36878013
DOI: 10.3201/eid2904.230046 -
Biomolecules Mar 2023The protein C is a small viral protein encoded in an overlapping frame of the P gene in the subfamily Orthoparamyxovirinae. This protein, expressed by alternative...
The protein C is a small viral protein encoded in an overlapping frame of the P gene in the subfamily Orthoparamyxovirinae. This protein, expressed by alternative translation initiation, is a virulence factor that regulates viral transcription, replication, and production of defective interfering RNA, interferes with the host-cell innate immunity systems and supports the assembly of viral particles and budding. We expressed and purified full-length and an N-terminally truncated C protein from Tupaia paramyxovirus (TupV) C protein (genus Narmovirus). We solved the crystal structure of the C-terminal part of TupV C protein at a resolution of 2.4 Å and found that it is structurally similar to Sendai virus C protein, suggesting that despite undetectable sequence conservation, these proteins are homologous. We characterized both truncated and full-length proteins by SEC-MALLS and SEC-SAXS and described their solution structures by ensemble models. We established a mini-replicon assay for the related Nipah virus (NiV) and showed that TupV C inhibited the expression of NiV minigenome in a concentration-dependent manner as efficiently as the NiV C protein. A previous study found that the Orthoparamyxovirinae C proteins form two clusters without detectable sequence similarity, raising the question of whether they were homologous or instead had originated independently. Since TupV C and SeV C are representatives of these two clusters, our discovery that they have a similar structure indicates that all Orthoparamyxovirine C proteins are homologous. Our results also imply that, strikingly, a STAT1-binding site is encoded by exactly the same RNA region of the P/C gene across Paramyxovirinae, but in different reading frames (P or C), depending on which cluster they belong to.
Topics: Scattering, Small Angle; X-Ray Diffraction; Nipah Virus; Immunity, Innate; RNA
PubMed: 36979390
DOI: 10.3390/biom13030455 -
Frontiers in Immunology 2022Retinoic acid-inducible gene I (RIG-I) is a receptor that senses viral RNA and interacts with mitochondrial antiviral signaling (MAVS) protein, leading to the production...
Retinoic acid-inducible gene I (RIG-I) is a receptor that senses viral RNA and interacts with mitochondrial antiviral signaling (MAVS) protein, leading to the production of type I interferons and inflammatory cytokines to establish an antiviral state. This signaling axis is initiated by the K63-linked RIG-I ubiquitination, mediated by E3 ubiquitin ligases such as TRIM25. However, many viruses, including several members of the family and human respiratory syncytial virus (HRSV), a member of the family , escape the immune system by targeting RIG-I/TRIM25 signaling. In this study, we screened human metapneumovirus (HMPV) open reading frames (ORFs) for their ability to block RIG-I signaling reconstituted in HEK293T cells by transfection with TRIM25 and RIG-I CARD (an N-terminal CARD domain that is constitutively active in RIG-I signaling). HMPV M2-2 was the most potent inhibitor of RIG-I/TRIM25-mediated interferon (IFN)-β activation. M2-2 silencing induced the activation of transcription factors (IRF and NF-kB) downstream of RIG-I signaling in A549 cells. Moreover, M2-2 inhibited RIG-I ubiquitination and CARD-dependent interactions with MAVS. Immunoprecipitation revealed that M2-2 forms a stable complex with RIG-I CARD/TRIM25 direct interaction with the SPRY domain of TRIM25. Similarly, HRSV NS1 also formed a stable complex with RIG-I CARD/TRIM25 and inhibited RIG-I ubiquitination. Notably, the inhibitory actions of HMPV M2-2 and HRSV NS1 are similar to those of V proteins of several members of the family. In this study, we have identified a novel mechanism of immune escape by HMPV, similar to that of and family members.
Topics: Antiviral Agents; DEAD Box Protein 58; HEK293 Cells; Humans; Immunity, Innate; Interferon Type I; Interferon-beta; Metapneumovirus; Paramyxoviridae; Paramyxoviridae Infections; Receptors, Immunologic; Transcription Factors; Tripartite Motif Proteins; Ubiquitin-Protein Ligases; Ubiquitination
PubMed: 36045682
DOI: 10.3389/fimmu.2022.970750 -
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 -
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 Mar 2020Recent high-throughput sequencing revealed that only 2% of the transcribed human genome codes for proteins, while the majority of transcriptional products are non-coding... (Review)
Review
Recent high-throughput sequencing revealed that only 2% of the transcribed human genome codes for proteins, while the majority of transcriptional products are non-coding RNAs (ncRNAs). Herein, we review the current knowledge regarding ncRNAs, both host- and virus-derived, and their role in respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infections. RSV is known as the most common cause of lower respiratory tract infection (LRTI) in children, while hMPV is also a significant contributor to LRTI in the pediatrics population. Although RSV and hMPV are close members, belonging to the family, they induce distinct changes in the ncRNA profile. Several types of host ncRNAs, including long ncRNA (lncRNA), microRNAs (miRNAs), and transfer RNA (tRNA)-derived RNA fragments (tRFs), are involved as playing roles in RSV and/or hMPV infection. Given the importance of ncRNAs in regulating the expression and functions of genes and proteins, comprehensively understanding the roles of ncRNAs in RSV/hMPV infection could shed light upon the disease mechanisms of RSV and hMPV, potentially providing insights into the development of prevention strategies and antiviral therapy. The presence of viral-derived RNAs and the potential of using ncRNAs as diagnostic biomarkers are also discussed in this review.
Topics: Animals; Biomarkers; Disease Resistance; Drug Discovery; Gene Expression Regulation; Host-Pathogen Interactions; Humans; Metapneumovirus; MicroRNAs; Paramyxoviridae Infections; RNA, Untranslated; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 32245206
DOI: 10.3390/v12030345 -
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