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Viruses Jan 2024Henipaviruses are a genus of emerging pathogens that includes the highly virulent Nipah and Hendra viruses that cause reoccurring outbreaks of disease. Henipaviruses... (Review)
Review
Henipaviruses are a genus of emerging pathogens that includes the highly virulent Nipah and Hendra viruses that cause reoccurring outbreaks of disease. Henipaviruses rely on two surface glycoproteins, known as the attachment and fusion proteins, to facilitate entry into host cells. As new and divergent members of the genus have been discovered and structurally characterized, key differences and similarities have been noted. This review surveys the available structural information on glycoproteins, complementing this with information from related biophysical and structural studies of the broader family of which Henipaviruses are members. The process of viral entry is a primary focus for vaccine and drug development, and this review aims to identify critical knowledge gaps in our understanding of the mechanisms that drive fusion.
Topics: Humans; Henipavirus; Nipah Virus; Henipavirus Infections; Glycoproteins; Hendra Virus
PubMed: 38399971
DOI: 10.3390/v16020195 -
Viruses May 2022is a viral family within the order of ; they are negative single-strand RNA viruses that can cause significant diseases in both humans and animals. In order to... (Review)
Review
is a viral family within the order of ; they are negative single-strand RNA viruses that can cause significant diseases in both humans and animals. In order to replicate, paramyxoviruses-as any other viruses-have to bypass an important protective mechanism developed by the host's cells: the defensive line driven by interferon. Once the viruses are recognized, the cells start the production of type I and type III interferons, which leads to the activation of hundreds of genes, many of which encode proteins with the specific function to reduce viral replication. Type II interferon is produced by active immune cells through a different signaling pathway, and activates a diverse range of genes with the same objective to block viral replication. As a result of this selective pressure, viruses have evolved different strategies to avoid the defensive function of interferons. The strategies employed by the different viral species to fight the interferon system include a number of sophisticated mechanisms. Here we analyzed the current status of the various strategies used by paramyxoviruses to subvert type I, II, and III interferon responses.
Topics: Animals; Antiviral Agents; Interferon-gamma; Interferons; Paramyxoviridae; Paramyxovirinae; RNA Viruses; Virus Replication
PubMed: 35632848
DOI: 10.3390/v14051107 -
Revue Scientifique Et Technique... Aug 2000Turkey rhinotracheitis, now commonly termed avian pneumovirus (APV) infection, is associated with serious welfare and economic problems in susceptible populations of... (Review)
Review
Turkey rhinotracheitis, now commonly termed avian pneumovirus (APV) infection, is associated with serious welfare and economic problems in susceptible populations of turkeys and probably also of chickens. The infection principally affects the upper respiratory tract, although egg-laying performance may also be affected in breeding turkeys. Secondary infections exacerbate the effects of the primary virus infection. The virus persists for only a short time both in the host and in the environment and is not known to be transmitted via the egg. Highly effective vaccines are available to control APV infections, and hence good biosecurity and careful use of these vaccines should enable infection to be controlled and spread restricted. Diagnosis and surveillance are normally performed serologically using enzyme-linked immunosorbent assays (ELISAs). Several different ELISA kits are available commercially, but these give variable results and are not wholly satisfactory since interpretation of results is difficult.
Topics: Animals; Chickens; Metapneumovirus; Paramyxoviridae Infections; Poultry Diseases; Turkeys
PubMed: 10935282
DOI: 10.20506/rst.19.2.1233 -
Clinical Microbiology Reviews Apr 2003Human parainfluenza viruses (HPIV) were first discovered in the late 1950s. Over the last decade, considerable knowledge about their molecular structure and function has... (Review)
Review
Human parainfluenza viruses (HPIV) were first discovered in the late 1950s. Over the last decade, considerable knowledge about their molecular structure and function has been accumulated. This has led to significant changes in both the nomenclature and taxonomic relationships of these viruses. HPIV is genetically and antigenically divided into types 1 to 4. Further major subtypes of HPIV-4 (A and B) and subgroups/genotypes of HPIV-1 and HPIV-3 have been described. HPIV-1 to HPIV-3 are major causes of lower respiratory infections in infants, young children, the immunocompromised, the chronically ill, and the elderly. Each subtype can cause somewhat unique clinical diseases in different hosts. HPIV are enveloped and of medium size (150 to 250 nm), and their RNA genome is in the negative sense. These viruses belong to the Paramyxoviridae family, one of the largest and most rapidly growing groups of viruses causing significant human and veterinary disease. HPIV are closely related to recently discovered megamyxoviruses (Hendra and Nipah viruses) and metapneumovirus.
Topics: Animals; Humans; Parainfluenza Virus 1, Human; Parainfluenza Virus 2, Human; Respirovirus Infections
PubMed: 12692097
DOI: 10.1128/CMR.16.2.242-264.2003 -
Viruses Jan 2020Paramyxovirus (PMV) entry requires the coordinated action of two envelope glycoproteins, the receptor binding protein (RBP) and fusion protein (F). The sequence of... (Review)
Review
Paramyxovirus (PMV) entry requires the coordinated action of two envelope glycoproteins, the receptor binding protein (RBP) and fusion protein (F). The sequence of events that occurs during the PMV entry process is tightly regulated. This regulation ensures entry will only initiate when the virion is in the vicinity of a target cell membrane. Here, we review recent structural and mechanistic studies to delineate the entry features that are shared and distinct amongst the . In general, we observe overarching distinctions between the protein-using RBPs and the sialic acid- (SA-) using RBPs, including how their stalk domains differentially trigger F. Moreover, through sequence comparisons, we identify greater structural and functional conservation amongst the PMV fusion proteins, as compared to the RBPs. When examining the relative contributions to sequence conservation of the globular head versus stalk domains of the RBP, we observe that, for the protein-using PMVs, the stalk domains exhibit higher conservation and find the opposite trend is true for SA-using PMVs. A better understanding of conserved and distinct features that govern the entry of protein-using versus SA-using PMVs will inform the rational design of broader spectrum therapeutics that impede this process.
Topics: Carrier Proteins; Humans; N-Acetylneuraminic Acid; Paramyxoviridae; Protein Binding; Viral Fusion Proteins; Virus Attachment; Virus Internalization
PubMed: 32019182
DOI: 10.3390/v12020161 -
GeroScience Oct 2022Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic zoonotic viruses of the genus Henipavirus, family Paramyxoviridae that cause severe disease outbreaks in... (Review)
Review
Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic zoonotic viruses of the genus Henipavirus, family Paramyxoviridae that cause severe disease outbreaks in humans and also can infect and cause lethal disease across a broad range of mammalian species. Another related Henipavirus has been very recently identified in China in febrile patients with pneumonia, the Langya virus (LayV) of probable animal origin in shrews. NiV and HeV were first identified as the causative agents of severe respiratory and encephalitic disease in the 1990s across Australia and Southern Asia with mortality rates reaching up to 90%. They are responsible for rare and sporadic outbreaks with no approved treatment modalities. NiV and HeV have wide cellular tropism that contributes to their high pathogenicity. From their natural hosts bats, different scenarios propitiate their spillover to pigs, horses, and humans. Henipavirus-associated respiratory disease arises from vasculitis and respiratory epithelial cell infection while the neuropathogenesis of Henipavirus infection is still not completely understood but appears to arise from dual mechanisms of vascular disease and direct parenchymal brain infection. This brief review offers an overview of direct and indirect mechanisms of HeV and NiV pathogenicity and their interaction with the human immune system, as well as the main viral strategies to subvert such responses.
Topics: Humans; Animals; Swine; Horses; Public Health; Henipavirus Infections; Nipah Virus; Hendra Virus; Mammals
PubMed: 36219280
DOI: 10.1007/s11357-022-00670-9 -
Viruses Sep 2021Syncytium formation, i.e., cell-cell fusion resulting in the formation of multinucleated cells, is a hallmark of infection by paramyxoviruses and other pathogenic... (Review)
Review
Syncytium formation, i.e., cell-cell fusion resulting in the formation of multinucleated cells, is a hallmark of infection by paramyxoviruses and other pathogenic viruses. This natural mechanism has historically been a diagnostic marker for paramyxovirus infection in vivo and is now widely used for the study of virus-induced membrane fusion in vitro. However, the role of syncytium formation in within-host dissemination and pathogenicity of viruses remains poorly understood. The diversity of henipaviruses and their wide host range and tissue tropism make them particularly appropriate models with which to characterize the drivers of syncytium formation and the implications for virus fitness and pathogenicity. Based on the henipavirus literature, we summarized current knowledge on the mechanisms driving syncytium formation, mostly acquired from in vitro studies, and on the in vivo distribution of syncytia. While these data suggest that syncytium formation widely occurs across henipaviruses, hosts, and tissues, we identified important data gaps that undermined our understanding of the role of syncytium formation in virus pathogenesis. Based on these observations, we propose solutions of varying complexity to fill these data gaps, from better practices in data archiving and publication for in vivo studies, to experimental approaches in vitro.
Topics: Giant Cells; HEK293 Cells; Henipavirus Infections; Host Specificity; Host-Pathogen Interactions; Humans; Membrane Fusion; Paramyxoviridae; Virus Attachment; Virus Internalization
PubMed: 34578336
DOI: 10.3390/v13091755 -
Current Opinion in Virology Jun 2017The paramyxovirus family comprises major human and animal pathogens such as measles virus (MeV), mumps virus (MuV), the parainfluenzaviruses, Newcastle disease virus... (Review)
Review
The paramyxovirus family comprises major human and animal pathogens such as measles virus (MeV), mumps virus (MuV), the parainfluenzaviruses, Newcastle disease virus (NDV), and the highly pathogenic zoonotic hendra (HeV) and nipah (NiV) viruses. Paramyxovirus particles are pleomorphic, with a lipid envelope, nonsegmented RNA genomes of negative polarity, and densely packed glycoproteins on the virion surface. A number of crystal structures of different paramyxovirus proteins and protein fragments were solved, but the available information concerning overall virion organization remains limited. However, recent studies have reported cryo-electron tomography-based reconstructions of Sendai virus (SeV), MeV, NDV, and human parainfluenza virus type 3 (HPIV3) particles and a surface assessment of NiV-derived virus-like particles (VLPs), which have yielded innovative hypotheses concerning paramyxovirus particle assembly, budding, and organization. Following a summary of the current insight into paramyxovirus virion morphology, this review will focus on discussing the implications of these particle reconstructions on the present models of paramyxovirus assembly and infection.
Topics: Cryoelectron Microscopy; Electron Microscope Tomography; Genome, Viral; Humans; Measles virus; Newcastle disease virus; Nipah Virus; Paramyxoviridae; Viral Fusion Proteins; Viral Matrix Proteins; Virion; Virus Assembly; Virus Release
PubMed: 28601688
DOI: 10.1016/j.coviro.2017.05.004 -
Viral Immunology Mar 2018Human parainfluenza viruses (family Paramyxoviridae), human metapneumovirus, and respiratory syncytial virus (family Pneumoviridae) infect most infants and children... (Review)
Review
Human parainfluenza viruses (family Paramyxoviridae), human metapneumovirus, and respiratory syncytial virus (family Pneumoviridae) infect most infants and children within the first few years of life and are the etiologic agents for many serious acute respiratory illnesses. These virus infections are also associated with long-term diseases that impact quality of life, including asthma. Despite over a half-century of vaccine research, development, and clinical trials, no vaccine has been licensed to date for the paramyxoviruses or pneumoviruses for the youngest infants. In this study, we describe the recent reclassification of paramyxoviruses and pneumoviruses into distinct families by the International Committee on the Taxonomy of Viruses. We also discuss some past unsuccessful vaccine trials and some currently preferred vaccine strategies. Finally, we discuss hurdles that must be overcome to support successful respiratory virus vaccine development for the youngest children.
Topics: Animals; Clinical Trials as Topic; Drug Discovery; Drug Evaluation, Preclinical; Humans; Paramyxoviridae Infections; Paramyxovirinae; Pneumovirinae; Respiratory Syncytial Virus Infections; Viral Vaccines
PubMed: 29323621
DOI: 10.1089/vim.2017.0137 -
Current Opinion in Immunology Aug 2022Viral proteins fold into a variety of structures as they perform their functions. Structure-based vaccine design aims to exploit knowledge of an antigen's architecture... (Review)
Review
Viral proteins fold into a variety of structures as they perform their functions. Structure-based vaccine design aims to exploit knowledge of an antigen's architecture to stabilize it in a vulnerable conformation. We summarize the general principles of structure-based vaccine design, with a focus on the major types of sequence modifications: proline, disulfide, cavity-filling, electrostatic and hydrogen-bond substitution, as well as domain deletion. We then review recent applications of these principles to vaccine-design efforts across five viral families: Coronaviridae, Orthomyxoviridae, Paramyxoviridae, Pneumoviridae, and Filoviridae. Outstanding challenges include continued application of proven design principles to pathogens of interest, as well as development of new strategies for those pathogens that resist traditional techniques.
Topics: Coronaviridae; Filoviridae; Humans; Orthomyxoviridae; Paramyxoviridae; Pneumovirinae; Vaccine Development; Viral Proteins; Viral Vaccines
PubMed: 35598506
DOI: 10.1016/j.coi.2022.102209