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https://www.readbyqxmd.com/read/28710694/ecology-of-filoviruses
#1
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
#2
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
#3
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 identified a 28-residue peptide (NP binding peptide, NPBP) from the Marburg virus (MARV) VP35 through sequence alignment with previously identified Ebola virus (EBOV) NPBP, which bound to the core region (residues 18-344) 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 non-polar interactions...
June 28, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28656706/on-the-structure-and-mechanism-of-two-pore-channels
#4
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
#5
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
#6
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
#7
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-as-an-anti-filoviral-entry-inhibitor
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28592526/novel-cross-reactive-monoclonal-antibodies-against-ebolavirus-glycoproteins-show-protection-in-a-murine-challenge-model
#14
Jim Duehr, Teddy John Wohlbold, Lisa Oestereich, Veronika Chromikova, Fatima Amanat, Madhusudan Rajendran, Sergio Gomez-Medina, Ignacio Mena, Benjamin R TenOever, Adolfo García-Sastre, Christopher F Basler, Cesar Munoz-Fontela, Florian Krammer
Out of an estimated 31,100 cases since its discovery in 1976, ebolaviruses have caused approximately 13,000 deaths. The vast majority (∼11,000) of these occurred during the 2013-2016 West African epidemic. Three out of five species in the genus are known to cause Ebola Virus Disease in humans. Several monoclonal antibodies against the ebolavirus glycoprotein are currently in development as therapeutics. However, there is still a paucity of monoclonal antibodies that can cross-react between the glycoproteins of different ebolavirus species and the mechanism of these monoclonal antibody therapeutics are still not understood in detail...
June 7, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28580138/plasma-membrane-association-facilitates-conformational-changes-in-the-marburg-virus-protein-vp40-dimer
#15
Nisha Bhattarai, Jeevan B Gc, Bernard S Gerstman, Robert V Stahelin, Prem P Chapagain
Filovirus infections cause hemorrhagic fever in humans and non-human primates that often results in high fatality rates. The Marburg virus is a lipid-enveloped virus from the Filoviridae family and is closely related to the Ebola virus. The viral matrix layer underneath the lipid envelope is formed by the matrix protein VP40 (VP40), which is also involved in other functions during the viral life-cycle. As in the Ebola virus VP40 (eVP40), the recently determined X-ray crystal structure of the Marburg virus VP40 (mVP40) features loops containing cationic residues that form a lipid binding basic patch...
April 26, 2017: RSC Advances
https://www.readbyqxmd.com/read/28573634/production-of-antigens-for-elisa
#16
Robert W Cross, Thomas G Ksiazek
Immunologic assays such as ELISA allow detection of either virus antigens or the host's immune response to antigens associated with prior infections and offer a powerful means to approach understanding the epidemiology and epizootiology of these agents. However, the success of these assays is highly dependent on the production of high-quality materials both to establish the assays (i.e., antigen target for antibody) and to serve as controls for establishing assay parameters and sensitivity. Here we describe methods for preparing ebolavirus antigens suitable for use as either reagents or controls in a variety of ELISA formats...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28573631/quantification-of-filovirus-glycoprotein-specific-antibodies
#17
Wakako Furuyama, Hiroko Miyamoto, Reiko Yoshida, Ayato Takada
Serological methods such as the enzyme-linked immunosorbent assay (ELISA) and virus neutralization test are fundamental tools used in diagnosis, seroepidemiological studies of filovirus transmission/prevalence, and the evaluation of vaccine immunogenicity and potential therapeutic antibodies. Filoviruses have a single transmembrane glycoprotein (GP), which is the only known target of neutralizing antibodies. Here we describe serological methods to quantify filovirus GP-specific antibodies.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28573622/assessment-of-inhibition-of-ebola-virus-progeny-production-by-antiviral-compounds
#18
Darryl Falzarano
Assessment of small molecule compounds against filoviruses, such as Ebola virus, has identified numerous compounds that appear to have antiviral activity and should presumably be further investigated in animal efficacy trials. However, despite the many compounds that are purported to have good antiviral activity in in vitro studies, there are few instances where any efficacy has been reported in nonhuman primate models. Many of the high-throughput screening assays use reporter systems that only recapitulate a portion of the virus life cycle, while other assays only assess antiviral activity at relatively early time points...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28573621/live-cell-imaging-of-filoviruses
#19
Gordian Schudt, Olga Dolnik, Stephan Becker
Observation of molecular processes inside living cells is fundamental to a deeper understanding of virus-host interactions in filoviral-infected cells. These observations can provide spatiotemporal insights into protein synthesis, protein-protein interaction dynamics, and transport processes of these highly pathogenic viruses. Thus, live-cell imaging provides the possibility for antiviral screening in real time and gives mechanistic insights into understanding filovirus assembly steps that are dependent on cellular factors, which then represent potential targets against this highly fatal disease...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28573619/generation-of-recombinant-ebola-viruses-using-reverse-genetics
#20
Allison Groseth
Reverse genetics systems encompass a wide array of tools aimed at recapitulating some or all of the virus life cycle. In their most complete form, full-length clone systems allow us to use plasmid-encoded versions of the ribonucleoprotein (RNP) components to initiate the transcription and replication of a plasmid-encoded version of the complete viral genome, thereby initiating the complete virus life cycle and resulting in infectious virus. As such this approach is ideal for the generation of tailor-made recombinant filoviruses, which can be used to study virus biology...
2017: Methods in Molecular Biology
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