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https://www.readbyqxmd.com/read/28922082/combinatorial-peptide-based-epitope-mapping-from-ebola-virus-dna-vaccines-and-infections-reveals-residue-level-determinants-of-antibody-binding
#1
Daniel R Ripoll, Daniel A J Mitchell, Lesley C Dupuy, Anders Wallqvist, Connie Schmaljohn, Sidhartha Chaudhury
Ebola virus (EBOV) infection is highly lethal and results in severe febrile bleeding disorders that affect humans and non-human primates. One of the therapeutic approaches for treating EBOV infection focus largely on cocktails of monoclonal antibodies (mAbs) that bind to specific regions of the EBOV glycoprotein (GP) and neutralize the virus. Recent structural studies using cryo-electron microscopy have identified key epitopes for several EBOV mAbs. While such information has yielded deep insights into antibody binding, limitations on resolution of these structures often preclude a residue-level analysis of EBOV epitopes...
September 18, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28918537/reverse-genetics-of-filoviruses
#2
Thomas Hoenen, Janine Brandt, Yíngyún Caì, Jens H Kuhn, Courtney Finch
Reverse genetics systems are used for the generation of recombinant viruses. For filoviruses, this technology has been available for more than 15 years and has been used to investigate questions regarding the molecular biology, pathogenicity, and host adaptation determinants of these viruses. Further, reporter-expressing, recombinant viruses are increasingly used as tools for screening for and characterization of candidate medical countermeasures. Thus, reverse genetics systems represent powerful research tools...
September 17, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28892520/knowledge-and-attitude-towards-ebola-and-marburg-virus-diseases-in-uganda-using-quantitative-and-participatory-epidemiology-techniques
#3
Luke Nyakarahuka, Eystein Skjerve, Daisy Nabadda, Doreen Chilolo Sitali, Chisoni Mumba, Frank N Mwiine, Julius J Lutwama, Stephen Balinandi, Trevor Shoemaker, Clovice Kankya
BACKGROUND: Uganda has reported five (5) Ebola virus disease outbreaks and three (3) Marburg virus disease outbreaks from 2000 to 2016. Peoples' knowledge and attitude towards Ebola and Marburg virus disease impact on control and prevention measures especially during outbreaks. We describe knowledge and attitude towards Ebola and Marburg virus outbreaks in two affected communities in Uganda to inform future outbreak responses and help in the design of health education and communication messages...
September 11, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28795188/filovirus-structural-biology-the-molecules-in-the-machine
#4
Robert N Kirchdoerfer, Hal Wasserman, Gaya K Amarasinghe, Erica Ollmann Saphire
In this chapter, we describe what is known thus far about the structures and functions of the handful of proteins encoded by filovirus genomes. Amongst the fascinating findings of the last decade is the plurality of functions and structures that these polypeptides can adopt. Many of the encoded proteins can play multiple, distinct roles in the virus life cycle, although the mechanisms by which these functions are determined and controlled remain mostly veiled. Further, some filovirus proteins are multistructural: adopting different oligomeric assemblies and sometimes, different tertiary structures to achieve their separate, and equally essential functions...
August 10, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28769016/favipiravir-t-705-a-broad-spectrum-inhibitor-of-viral-rna-polymerase
#5
Yousuke Furuta, Takashi Komeno, Takaaki Nakamura
Favipiravir (T-705; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) is an anti-viral agent that selectively and potently inhibits the RNA-dependent RNA polymerase (RdRp) of RNA viruses. Favipiravir was discovered through screening chemical library for anti-viral activity against the influenza virus by Toyama Chemical Co., Ltd. Favipiravir undergoes an intracellular phosphoribosylation to be an active form, favipiravir-RTP (favipiravir ribofuranosyl-5'-triphosphate), which is recognized as a substrate by RdRp, and inhibits the RNA polymerase activity...
2017: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/28766193/filovirus-research-how-it-began
#6
Werner Slenczka
The first reported filovirus outbreak occurred in August 1967, when laboratory workers in Marburg and Frankfurt, Germany, and Belgrade, Yugoslavia (now Serbia) became infected with an unknown highly pathogenic agent. The disease was characterized by high fever, malaise, rash, hemorrhagic and tetanic manifestations, and high lethality, amounting to 25%. The disease was introduced to Europe by grivets (Chlorocebus aethiops), which were used for biomedical research and vaccine production. The causative agent, Marburg virus, was isolated and identified by scientists of the University of Marburg, Germany in cooperation with specialists for viral electron microscopy at the Bernhard Nocht Institute in Hamburg, Germany...
August 2, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28724616/marburg-virus-survivor-immune-responses-are-th1-skewed-with-limited-neutralizing-antibody-responses
#7
Spencer W Stonier, Andrew S Herbert, Ana I Kuehne, Ariel Sobarzo, Polina Habibulin, Chen V Abramovitch Dahan, Rebekah M James, Moses Egesa, Stephen Cose, Julius Julian Lutwama, Leslie Lobel, John M Dye
Until recently, immune responses in filovirus survivors remained poorly understood. Early studies revealed IgM and IgG responses to infection with various filoviruses, but recent outbreaks have greatly expanded our understanding of filovirus immune responses. Immune responses in survivors of Ebola virus (EBOV) and Sudan virus (SUDV) infections have provided the most insight, with T cell responses as well as detailed antibody responses having been characterized. Immune responses to Marburg virus (MARV), however, remain almost entirely uncharacterized...
September 4, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28710694/ecology-of-filoviruses
#8
Brian R Amman, Robert Swanepoel, Stuart T Nichol, Jonathan S Towner
Filoviruses can cause severe and often fatal disease in humans. To date, there have been 47 outbreaks resulting in more than 31,500 cases of human illness and over 13,200 reported deaths. Since their discovery, researchers from many scientific disciplines have worked to better understand the natural history of these deadly viruses. Citing original research wherever possible, this chapter reviews laboratory and field-based studies on filovirus ecology and summarizes efforts to identify where filoviruses persist in nature, how virus is transmitted to other animals and ultimately, what drivers cause spillover to human beings...
July 15, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28685291/filovirus-strategies-to-escape-antiviral-responses
#9
Judith Olejnik, Adam J Hume, Daisy W Leung, Gaya K Amarasinghe, Christopher F Basler, Elke Mühlberger
This chapter describes the various strategies filoviruses use to escape host immune responses with a focus on innate immune and cell death pathways. Since filovirus replication can be efficiently blocked by interferon (IFN), filoviruses have evolved mechanisms to counteract both type I IFN induction and IFN response signaling pathways. Intriguingly, marburg- and ebolaviruses use different strategies to inhibit IFN signaling. This chapter also summarizes what is known about the role of IFN-stimulated genes (ISGs) in filovirus infection...
July 8, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28659479/crystal-structure-of-the-marburg-virus-nucleoprotein-core-domain-chaperoned-by-a-vp35-peptide-reveals-a-conserved-drug-target-for-filovirus
#10
Tengfei Zhu, Hao Song, Ruchao Peng, Yi Shi, Jianxun Qi, George F Gao
Filovirus nucleoprotein (NP), viral protein 35 (VP35), and polymerase L are essential for viral replication and nucleocapsid formation. Here, we identify a 28-residue peptide (NP binding peptide [NPBP]) from Marburg virus (MARV) VP35 through sequence alignment with previously identified Ebola virus (EBOV) NPBP, which bound to the core region (residues 18 to 344) of the N-terminal portion of MARV NP with high affinity. The crystal structure of the MARV NP core/NPBP complex at a resolution of 2.6 Å revealed that NPBP binds to the C-terminal region of the NP core via electrostatic and nonpolar interactions...
September 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28656706/on-the-structure-and-mechanism-of-two-pore-channels
#11
REVIEW
Alexander F Kintzer, Robert M Stroud
In eukaryotes, two-pore channels (TPC1-3) comprise a family of ion channels that regulate the conductance of Na(+) and Ca(2+) ions across cellular membranes. TPC1-3 form endolysosomal channels, but TPC3 can also function in the plasma membrane. TPC1/3 are voltage-gated channels, but TPC2 opens in response to binding endolysosome-specific lipid phosphatidylinositol-3,5-diphosphate (PI(3,5)P2 ). Filoviruses, such as Ebola, exploit TPC-mediated ion release as a means of escape from the endolysosome during infection...
June 28, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28653190/therapeutics-against-filovirus-infection
#12
John Connor, Gary Kobinger, Gene Olinger
Therapies for filovirus infections are urgently needed. The paradoxical issue facing therapies is the need for rigorous safety and efficacy testing, adhering to the principle tenant of medicine to do no harm, while responding to the extreme for a treatment option during an outbreak. Supportive care remains a primary goal for infected patients. Years of research into filoviruses has provided possible medical interventions ranging from direct antivirals, host-factor supportive approaches, and passive immunity...
June 27, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28653189/small-animal-models-for-studying-filovirus-pathogenesis
#13
Satoko Yamaoka, Logan Banadyga, Mike Bray, Hideki Ebihara
Filovirus small animal disease models have so far been developed in laboratory mice, guinea pigs, and hamsters. Since immunocompetent rodents do not exhibit overt signs of disease following infection with wild-type filoviruses isolated from humans, rodent models have been established using adapted viruses produced through sequential passage in rodents. Rodent-adapted viruses target the same cells/tissues as the wild-type viruses, making rodents invaluable basic research tools for studying filovirus pathogenesis...
June 27, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28653188/guide-to-the-correct-use-of-filoviral-nomenclature
#14
Jens H Kuhn
The International Committee on Taxonomy of Viruses (ICTV) currently recognizes three genera and seven species as part of the mononegaviral family Filoviridae. Eight distinct filoviruses (Bundibugyo virus, Ebola virus, Lloviu virus, Marburg virus, Ravn virus, Reston virus, Sudan virus, and Taï Forest virus) have been assigned to these seven species. This chapter briefly summarizes the status quo of filovirus classification and focuses on the importance of differentiating between filoviral species and filoviruses and the correct use of taxonomic and vernacular filovirus names and abbreviations in written and oral discourse...
June 27, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28645623/identification-of-a-coumarin-based-antihistamine-like-small-molecule-as-an-anti-filoviral-entry-inhibitor
#15
Han Cheng, Adam Schafer, Veronica Soloveva, Dima Gharaibeh, Tara Kenny, Cary Retterer, Rouzbeh Zamani, Sina Bavari, Norton P Peet, Lijun Rong
Filoviruses, consisting of Ebola virus, Marburg virus and Cuevavirus, cause severe hemorrhagic fevers in humans with high mortality rates up to 90%. Currently, there is no approved vaccine or therapy available for the prevention and treatment of filovirus infection in humans. The recent 2013-2015 West African Ebola epidemic underscores the urgency to develop antiviral therapeutics against these infectious diseases. Our previous study showed that GPCR antagonists, particularly histamine receptor antagonists (antihistamines) inhibit Ebola and Marburg virus entry...
June 20, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28636653/the-ebola-virus-vp35-protein-binds-viral-immunostimulatory-and-host-rnas-identified-through-deep-sequencing
#16
Kari A Dilley, Alexander A Voorhies, Priya Luthra, Vinita Puri, Timothy B Stockwell, Hernan Lorenzi, Christopher F Basler, Reed S Shabman
Ebola virus and Marburg virus are members of the Filovirdae family and causative agents of hemorrhagic fever with high fatality rates in humans. Filovirus virulence is partially attributed to the VP35 protein, a well-characterized inhibitor of the RIG-I-like receptor pathway that triggers the antiviral interferon (IFN) response. Prior work demonstrates the ability of VP35 to block potent RIG-I activators, such as Sendai virus (SeV), and this IFN-antagonist activity is directly correlated with its ability to bind RNA...
2017: PloS One
https://www.readbyqxmd.com/read/28622346/flavivirus-and-filovirus-evoprinters-new-alignment-tools-for-the-comparative-analysis-of-viral-evolution
#17
Thomas Brody, Amarendra S Yavatkar, Dong Sun Park, Alexander Kuzin, Jermaine Ross, Ward F Odenwald
BACKGROUND: Flavivirus and Filovirus infections are serious epidemic threats to human populations. Multi-genome comparative analysis of these evolving pathogens affords a view of their essential, conserved sequence elements as well as progressive evolutionary changes. While phylogenetic analysis has yielded important insights, the growing number of available genomic sequences makes comparisons between hundreds of viral strains challenging. We report here a new approach for the comparative analysis of these hemorrhagic fever viruses that can superimpose an unlimited number of one-on-one alignments to identify important features within genomes of interest...
June 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28603449/filoviruses-and-bats
#18
Amy J Schuh, Brian R Amman, Jonathan S Towner
While Reston and Lloviu viruses have never been associated with human disease, the other filoviruses cause outbreaks of hemorrhagic fever characterised by person-to-person transmission and high case fatality ratios. Cumulative evidence suggests that bats are the most likely reservoir hosts of the filoviruses. Ecological investigations following Marburg virus disease outbreaks associated with entry into caves inhabited by Rousettus aegyptiacus bats led to the identification of this bat species as the natural reservoir host of the marburgviruses...
March 2017: Microbiology Australia
https://www.readbyqxmd.com/read/28601948/inside-the-cell-assembly-of-filoviruses
#19
Larissa Kolesnikova, Asuka Nanbo, Stephan Becker, Yoshihiro Kawaoka
This chapter reviews our current knowledge about the spatiotemporal assembly of filoviral particles. We will follow particles from nucleocapsid entry into the cytoplasm until the nucleocapsids are enveloped at the plasma membrane. We will also highlight the currently open scientific questions surrounding filovirus assembly.
June 11, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28601947/mechanisms-of-filovirus-entry
#20
R A Davey, O Shtanko, M Anantpadma, Y Sakurai, K Chandran, W Maury
Filovirus entry into cells is complex, perhaps as complex as any viral entry mechanism identified to date. However, over the past 10 years, the important events required for filoviruses to enter into the endosomal compartment and fuse with vesicular membranes have been elucidated (Fig. 1). Here, we highlight the important steps that are required for productive entry of filoviruses into mammalian cells.
June 11, 2017: Current Topics in Microbiology and Immunology
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