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Viruses Jan 2023The order contains a variety of highly pathogenic viruses that may infect humans, including the families , , , and . Animal models have historically been important to... (Review)
Review
The order contains a variety of highly pathogenic viruses that may infect humans, including the families , , , and . Animal models have historically been important to study virus pathogenicity and to develop medical countermeasures. As these have inherent shortcomings, the rise of microphysiological systems and organoids able to recapitulate hallmarks of the diseases caused by these viruses may have enormous potential to add to or partially replace animal modeling in the future. Indeed, microphysiological systems and organoids are already used in the pharmaceutical R&D pipeline because they are prefigured to overcome the translational gap between model systems and clinical studies. Moreover, they may serve to alleviate ethical concerns related to animal research. In this review, we discuss the value of animal model alternatives in human pathogenic filovirus and bornavirus research. The current animal models and their limitations are presented followed by an overview of existing alternatives, such as organoids and microphysiological systems, which might help answering open research questions.
Topics: Animals; Humans; Filoviridae; Bornaviridae; Models, Animal
PubMed: 36680198
DOI: 10.3390/v15010158 -
Biochimica Et Biophysica Acta.... Dec 2020Viruses reshape the organization of the cell interior to achieve different steps of their cellular cycle. Particularly, viral replication and assembly often take place... (Review)
Review
Viruses reshape the organization of the cell interior to achieve different steps of their cellular cycle. Particularly, viral replication and assembly often take place in viral factories where specific viral and cellular proteins as well as nucleic acids concentrate. Viral factories can be either membrane-delimited or devoid of any cellular membranes. In the latter case, they are referred as membrane-less replication compartments. The most emblematic ones are the Negri bodies, which are inclusion bodies that constitute the hallmark of rabies virus infection. Interestingly, Negri bodies and several other viral replication compartments have been shown to arise from a liquid-liquid phase separation process and, thus, constitute a new class of liquid organelles. This is a paradigm shift in the field of virus replication. Here, we review the different aspects of membrane-less virus replication compartments with a focus on the Mononegavirales order and discuss their interactions with the host cell machineries and the cytoskeleton. We particularly examine the interplay between viral factories and the cellular innate immune response, of which several components also form membrane-less condensates in infected cells.
Topics: Cell Membrane; Inclusion Bodies, Viral; Rabies; Rabies virus; Viral Proteins; Viral Replication Compartments; Virus Replication
PubMed: 32835749
DOI: 10.1016/j.bbamcr.2020.118831 -
International Journal of Molecular... Jan 2018Bat rabies cases in Europe are mainly attributed to two lyssaviruses, namely European Bat Lyssavirus 1 (EBLV-1) and European Bat Lyssavirus 2 (EBLV-2). Prior to the... (Review)
Review
Bat rabies cases in Europe are mainly attributed to two lyssaviruses, namely European Bat Lyssavirus 1 (EBLV-1) and European Bat Lyssavirus 2 (EBLV-2). Prior to the death of a bat worker in Finland in 1985, very few bat rabies cases were reported. Enhanced surveillance in the two subsequent years (1986-1987) identified 263 cases (more than a fifth of all reported cases to date). Between 1977 and 2016, 1183 cases of bat rabies were reported, with the vast majority (>97%) being attributed to EBLV-1. In contrast, there have been only 39 suspected cases of EBLV-2, of which 34 have been confirmed by virus typing and presently restricted to just two bat species; and . The limited number of EBLV-2 cases in Europe prompted the establishment of a network of European reference laboratories to collate all available viruses and data. Despite the relatively low number of EBLV-2 cases, a large amount of anomalous data has been published in the scientific literature, which we have here reviewed and clarified. In this review, 29 EBLV-2 full genome sequences have been analysed to further our understanding of the diversity and molecular evolution of EBLV-2 in Europe. Analysis of the 29 complete EBLV-2 genome sequences clearly corroborated geographical relationships with all EBLV-2 sequences clustering at the country level irrespective of the gene studied. Further geographical clustering was also observed at a local level. There are high levels of homogeneity within the EBLV-2 species with nucleotide identities ranging from 95.5-100% and amino acid identities between 98.7% and 100%, despite the widespread distribution of the isolates both geographically and chronologically. The mean substitution rate for EBLV-2 across the five concatenated genes was 1.65 × 10, and evolutionary clock analysis confirms the slow evolution of EBLV-2 both between and within countries in Europe. This is further supported by the first detailed EBLV-2 intra-roost genomic analysis whereby a relatively high sequence homogeneity was found across the genomes of three EBLV-2 isolates obtained several years apart (2007, 2008, and 2014) from at the same site (Stokesay Castle, Shropshire, UK).
Topics: Animals; Evolution, Molecular; Genome, Viral; Humans; Lyssavirus; Philology; Rhabdoviridae Infections
PubMed: 29303971
DOI: 10.3390/ijms19010156 -
The Journal of General Virology Jul 2021Members of the family produce enveloped virions containing a linear negative-sense non-segmented RNA genome of about 9 kb. Bornaviruses are found in mammals, birds,...
Members of the family produce enveloped virions containing a linear negative-sense non-segmented RNA genome of about 9 kb. Bornaviruses are found in mammals, birds, reptiles and fish. The most-studied viruses with public health and veterinary impact are Borna disease virus 1 and variegated squirrel bornavirus 1, both of which cause fatal encephalitis in humans. Several orthobornaviruses cause neurological and intestinal disorders in birds, mostly parrots. Endogenous bornavirus-like sequences occur in the genomes of various animals. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family , which is available at ictv.global/report/bornaviridae.
Topics: Animals; Borna Disease; Borna disease virus; Bornaviridae; Genome, Viral; Host Specificity; Humans; Virion; Virus Replication
PubMed: 34227935
DOI: 10.1099/jgv.0.001613 -
Viruses Sep 2015The family Filoviridae contains several of the most deadly pathogens known to date and the current Ebola virus disease (EVD) outbreak in Western Africa, due to Ebola... (Review)
Review
The family Filoviridae contains several of the most deadly pathogens known to date and the current Ebola virus disease (EVD) outbreak in Western Africa, due to Ebola virus (EBOV) infection, highlights the need for active and broad research into filovirus pathogenesis. However, in comparison, the seven other known filovirus family members are significantly understudied. Many of these, including Marburgviruses and Ebolaviruses other than EBOV, are also highly virulent and fully capable of causing widespread epidemics. This review places the focus on these non-EBOV filoviruses, including known immunological and pathological data. The available animal models, research tools and currently available therapeutics will also be discussed along with an emphasis in the large number of current gaps in knowledge of these less highlighted filoviruses. It is evident that much research is yet to be done in order to bring the non-EBOV filovirus field to the forefront of current research and, importantly, to the development of more effective vaccines and therapeutics to combat potential future outbreaks.
Topics: Animals; Biomedical Research; Disease Models, Animal; Disease Outbreaks; Filoviridae; Filoviridae Infections; Humans; Virulence
PubMed: 26426036
DOI: 10.3390/v7102867 -
Viruses Mar 2021Lagos bat virus (LBV), one of the 17 accepted viral species of the genus, was the first rabies-related virus described in 1956. This virus is endemic to the African... (Review)
Review
Lagos bat virus (LBV), one of the 17 accepted viral species of the genus, was the first rabies-related virus described in 1956. This virus is endemic to the African continent and is rarely encountered. There are currently four lineages, although the observed genetic diversity exceeds existing lyssavirus species demarcation criteria. Several exposures to rabid bats infected with LBV have been reported; however, no known human cases have been reported to date. This review provides the history of LBV and summarizes previous knowledge as well as new detections. Genetic diversity, pathogenesis and prevention are re-evaluated and discussed.
Topics: Animals; Chiroptera; Genetic Variation; Humans; Lyssavirus; Phylogeny; Rabies; Rhabdoviridae Infections; South Africa
PubMed: 33805487
DOI: 10.3390/v13040576 -
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 -
Viruses May 2023Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic species from the genus within the paramyxovirus family and are harbored by Flying Fox species....
Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic species from the genus within the paramyxovirus family and are harbored by Flying Fox species. Henipaviruses cause severe respiratory disease, neural symptoms, and encephalitis in various animals and humans, with human mortality rates exceeding 70% in some NiV outbreaks. The henipavirus matrix protein (M), which drives viral assembly and budding of the virion, also performs non-structural functions as a type I interferon antagonist. Interestingly, M also undergoes nuclear trafficking that mediates critical monoubiquitination for downstream cell sorting, membrane association, and budding processes. Based on the NiV and HeV M X-ray crystal structures and cell-based assays, M possesses a putative monopartite nuclear localization signal (NLS) (residues KRKKIR; NLS1 HeV), positioned on an exposed flexible loop and typical of how many NLSs bind importin alpha (IMPα), and a putative bipartite NLS (RR-10X-KRK; NLS2 HeV), positioned within an α-helix that is far less typical. Here, we employed X-ray crystallography to determine the binding interface of these M NLSs and IMPα. The interaction of both NLS peptides with IMPα was established, with NLS1 binding the IMPα major binding site, and NLS2 binding as a non-classical NLS to the minor site. Co-immunoprecipitation (co-IP) and immunofluorescence assays (IFA) confirm the critical role of NLS2, and specifically K258. Additionally, localization studies demonstrated a supportive role for NLS1 in M nuclear localization. These studies provide additional insight into the critical mechanisms of M nucleocytoplasmic transport, the study of which can provide a greater understanding of viral pathogenesis and uncover a potential target for novel therapeutics for henipaviral diseases.
Topics: Animals; Humans; Nuclear Localization Signals; Active Transport, Cell Nucleus; Nipah Virus; alpha Karyopherins; Hendra Virus; Henipavirus Infections; Protein Binding
PubMed: 37376602
DOI: 10.3390/v15061302 -
Viruses Mar 2020Paramyxoviruses and pneumoviruses infect cells through fusion (F) protein-mediated merger of the viral envelope with target membranes. Members of these families include... (Review)
Review
Paramyxoviruses and pneumoviruses infect cells through fusion (F) protein-mediated merger of the viral envelope with target membranes. Members of these families include a range of major human and animal pathogens, such as respiratory syncytial virus (RSV), measles virus (MeV), human parainfluenza viruses (HPIVs), and highly pathogenic Nipah virus (NiV). High-resolution F protein structures in both the metastable pre- and the postfusion conformation have been solved for several members of the families and a number of F-targeting entry inhibitors have progressed to advanced development or clinical testing. However, small-molecule RSV entry inhibitors have overall disappointed in clinical trials and viral resistance developed rapidly in experimental settings and patients, raising the question of whether the available structural information may provide a path to counteract viral escape through proactive inhibitor engineering. This article will summarize current mechanistic insight into F-mediated membrane fusion and examine the contribution of structural information to the development of small-molecule F inhibitors. Implications are outlined for future drug target selection and rational drug engineering strategies.
Topics: Animals; Antiviral Agents; Binding Sites; Drug Discovery; Humans; Models, Molecular; Paramyxoviridae Infections; Paramyxovirinae; Pneumovirus; Pneumovirus Infections; Protein Binding; Structure-Activity Relationship; Virus Internalization
PubMed: 32245118
DOI: 10.3390/v12030342 -
Vector Borne and Zoonotic Diseases... Sep 2022Outbreaks of African filoviruses often have high mortality, including more than 11,000 deaths among 28,562 cases during the West Africa Ebola outbreak of 2014-2016.... (Review)
Review
Outbreaks of African filoviruses often have high mortality, including more than 11,000 deaths among 28,562 cases during the West Africa Ebola outbreak of 2014-2016. Numerous studies have investigated the factors that contributed to individual filovirus outbreaks, but there has been little quantitative synthesis of this work. In addition, the ways in which the typical causes of filovirus outbreaks differ from other zoonoses remain poorly described. In this study, we quantify factors associated with 45 outbreaks of African filoviruses (ebolaviruses and Marburg virus) using a rubric of 48 candidate causal drivers. For filovirus outbreaks, we reviewed >700 peer-reviewed and gray literature sources and developed a list of the factors reported to contribute to each outbreak (, a "driver profile" for each outbreak). We compare and contrast the profiles of filovirus outbreaks to 200 background outbreaks, randomly selected from a global database of 4463 outbreaks of bacterial and viral zoonotic diseases. We also test whether the quantitative patterns that we observed were robust to the influences of six covariates, country-level factors such as gross domestic product, population density, and latitude that have been shown to bias global outbreak data. We find that, regardless of whether covariates are included or excluded from models, the driver profile of filovirus outbreaks differs from that of background outbreaks. Socioeconomic factors such as trade and travel, wild game consumption, failures of medical procedures, and deficiencies in human health infrastructure were more frequently reported in filovirus outbreaks than in the comparison group. Based on our results, we also present a review of drivers reported in at least 10% of filovirus outbreaks, with examples of each provided.
Topics: Animals; Disease Outbreaks; Ebolavirus; Hemorrhagic Fever, Ebola; Humans; Marburg Virus Disease; Marburgvirus
PubMed: 36084314
DOI: 10.1089/vbz.2022.0020