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https://www.readbyqxmd.com/read/27908828/assessment-of-the-potential-for-host-targeted-iminosugars-uv-4-and-uv-5-activity-against-filovirus-infections-in-vitro-and-in-vivo
#1
Kelly L Warfield, Travis K Warren, Xiangguo Qiu, Jay Wells, Chad E Mire, Joan B Geisbert, Kelly S Stuthman, Nicole L Garza, Sean A Van Tongeren, Amy C Shurtleff, Krystle N Agans, Gary Wong, Michael V Callahan, Thomas W Geisbert, Brennan Klose, Urban Ramstedt, Anthony M Treston
Iminosugars are host-directed antivirals with broad-spectrum activity. The iminosugar, N-butyl-deoxynojirimycin (NB-DNJ or Miglustat(®)), is used in humans for treatment of Gaucher's disease and has mild antiviral properties. More potent analogs of NB-DNJ have been generated and have demonstrated activity against a variety of viruses including flaviviruses, influenza, herpesviruses and filoviruses. In the current study, a panel of analogs based on NB-DNJ was analyzed for activity against Ebola (EBOV) and Marburg viruses (MARV)...
November 28, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27902321/the-serology-of-ebolavirus-a-wider-geographical-range-a-wider-genus-of-viruses-or-a-wider-range-of-virulence
#2
Magdalena Formella, Derek Gatherer
Viruses of the genus Ebolavirus are the causative agents of Ebola virus disease (EVD), of which there have been only 25 recorded outbreaks since the discovery of Zaire and Sudan ebolaviruses in the late 1970s. Until the west African outbreak commencing in late 2013, EVD was confined to an area of central Africa stretching from the coast of Gabon through the Congo river basin and eastward to the Great Lakes. Nevertheless, population serological studies since 1976, most of which were carried out in the first two decades after that date, have suggested a wider distribution and more frequent occurrence across tropical Africa...
October 21, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27887599/how-severe-and-prevalent-are-ebola-and-marburg-viruses-a-systematic-review-and-meta-analysis-of-the-case-fatality-rates-and-seroprevalence
#3
Luke Nyakarahuka, Clovice Kankya, Randi Krontveit, Benjamin Mayer, Frank N Mwiine, Julius Lutwama, Eystein Skjerve
BACKGROUND: Ebola and Marburg virus diseases are said to occur at a low prevalence, but are very severe diseases with high lethalities. The fatality rates reported in different outbreaks ranged from 24-100%. In addition, sero-surveys conducted have shown different seropositivity for both Ebola and Marburg viruses. We aimed to use a meta-analysis approach to estimate the case fatality and seroprevalence rates of these filoviruses, providing vital information for epidemic response and preparedness in countries affected by these diseases...
November 25, 2016: BMC Infectious Diseases
https://www.readbyqxmd.com/read/27847355/crystal-structure-of-the-marburg-virus-vp35-oligomerization-domain
#4
Jessica F Bruhn, Robert N Kirchdoerfer, Sarah M Urata, Sheng Li, Ian J Tickle, Gérard Bricogne, Erica Ollmann Saphire
: Marburg virus (MARV) is a highly pathogenic filovirus that is classified in a distinct genus from Ebola virus (EBOV) (genera Marburgvirus and Ebolavirus). Both viruses produce a multifunctional protein termed VP35, which acts as a polymerase co-factor, a viral protein chaperone and an antagonist of the innate immune response. VP35 contains a central oligomerization domain with a predicted coiled-coil motif. This domain has been shown to be essential for RNA polymerase function. Here we present crystal structures of the MARV VP35 oligomerization domain...
November 9, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27755595/the-ebola-virus-vp30-np-interaction-is-a-regulator-of-viral-rna-synthesis
#5
Robert N Kirchdoerfer, Crystal L Moyer, Dafna M Abelson, Erica Ollmann Saphire
Filoviruses are capable of causing deadly hemorrhagic fevers. All nonsegmented negative-sense RNA-virus nucleocapsids are composed of a nucleoprotein (NP), a phosphoprotein (VP35) and a polymerase (L). However, the VP30 RNA-synthesis co-factor is unique to the filoviruses. The assembly, structure, and function of the filovirus RNA replication complex remain unclear. Here, we have characterized the interactions of Ebola, Sudan and Marburg virus VP30 with NP using in vitro biochemistry, structural biology and cell-based mini-replicon assays...
October 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27746072/comparative-phylogeography-of-african-fruit-bats-chiroptera-pteropodidae-provide-new-insights-into-the-outbreak-of-ebola-virus-disease-in-west-africa-2014-2016
#6
Alexandre Hassanin, Nicolas Nesi, Julie Marin, Blaise Kadjo, Xavier Pourrut, Éric Leroy, Guy-Crispin Gembu, Prescott Musaba Akawa, Carine Ngoagouni, Emmanuel Nakouné, Manuel Ruedi, Didier Tshikung, Célestin Pongombo Shongo, Céline Bonillo
Both Ebolavirus and Marburgvirus were detected in several fruit bat species of the family Pteropodidae, suggesting that this taxon plays a key role in the life cycle of filoviruses. After four decades of Zaire Ebolavirus (ZEBOV) outbreaks in Central Africa, the virus was detected for the first time in West Africa in 2014. To better understand the role of fruit bats as potential reservoirs and circulating hosts between Central and West Africa, we examine here the phylogeny and comparative phylogeography of Pteropodidae...
October 13, 2016: Comptes Rendus Biologies
https://www.readbyqxmd.com/read/27713552/differential-transcriptional-responses-to-ebola-and-marburg-virus-infection-in-bat-and-human-cells
#7
Martin Hölzer, Verena Krähling, Fabian Amman, Emanuel Barth, Stephan H Bernhart, Victor A O Carmelo, Maximilian Collatz, Gero Doose, Florian Eggenhofer, Jan Ewald, Jörg Fallmann, Lasse M Feldhahn, Markus Fricke, Juliane Gebauer, Andreas J Gruber, Franziska Hufsky, Henrike Indrischek, Sabina Kanton, Jörg Linde, Nelly Mostajo, Roman Ochsenreiter, Konstantin Riege, Lorena Rivarola-Duarte, Abdullah H Sahyoun, Sita J Saunders, Stefan E Seemann, Andrea Tanzer, Bertram Vogel, Stefanie Wehner, Michael T Wolfinger, Rolf Backofen, Jan Gorodkin, Ivo Grosse, Ivo Hofacker, Steve Hoffmann, Christoph Kaleta, Peter F Stadler, Stephan Becker, Manja Marz
The unprecedented outbreak of Ebola in West Africa resulted in over 28,000 cases and 11,000 deaths, underlining the need for a better understanding of the biology of this highly pathogenic virus to develop specific counter strategies. Two filoviruses, the Ebola and Marburg viruses, result in a severe and often fatal infection in humans. However, bats are natural hosts and survive filovirus infections without obvious symptoms. The molecular basis of this striking difference in the response to filovirus infections is not well understood...
October 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27707924/tetherin-antagonism-by-the-ebola-virus-glycoprotein-requires-an-intact-receptor-binding-domain-and-can-be-blocked-by-gp1-specific-antibodies
#8
Constantin Brinkmann, Inga Nehlmeier, Kerstin Walendy-Gnirß, Julia Nehls, Mariana González Hernández, Markus Hoffmann, Xiangguo Qiu, Ayato Takada, Michael Schindler, Stefan Pöhlmann
: The glycoprotein of Ebola virus (EBOV-GP), a member of the Filoviridae family, facilitates viral entry into target cells. In addition, EBOV-GP antagonizes the antiviral activity of the host cell protein tetherin, which may otherwise restrict EBOV-release from infected cells. However, it is unclear how EBOV-GP antagonizes tetherin and it is unknown whether the GP of Lloviu virus (LLOV), a filovirus found in dead bats in Northern Spain, also counteracts tetherin. Here, we show that LLOV-GP antagonizes tetherin, indicating that tetherin may not impede LLOV spread in human cells...
October 5, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27703185/epigraph-a-vaccine-design-tool-applied-to-an-hiv-therapeutic-vaccine-and-a-pan-filovirus-vaccine
#9
James Theiler, Hyejin Yoon, Karina Yusim, Louis J Picker, Klaus Fruh, Bette Korber
Epigraph is an efficient graph-based algorithm for designing vaccine antigens to optimize potential T-cell epitope (PTE) coverage. Epigraph vaccine antigens are functionally similar to Mosaic vaccines, which have demonstrated effectiveness in preliminary HIV non-human primate studies. In contrast to the Mosaic algorithm, Epigraph is substantially faster, and in restricted cases, provides a mathematically optimal solution. Epigraph furthermore has new features that enable enhanced vaccine design flexibility...
October 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27686015/toward-an-effective-ebola-virus-vaccine
#10
Rohan Keshwara, Reed F Johnson, Matthias J Schnell
Long-term control of viral outbreaks requires the use of vaccines to impart acquired resistance and ensuing protection. In the wake of an epidemic, established immunity against a particular disease can limit spread and significantly decrease mortality. Creation of a safe and efficacious vaccine against Ebola virus (EBOV) has proven elusive so far, but various inventive strategies are now being employed to counteract the threat of outbreaks caused by EBOV and related filoviruses. Here, we present a current overview of progress in the field of Ebola virus vaccine development...
September 28, 2016: Annual Review of Medicine
https://www.readbyqxmd.com/read/27670273/could-bat-cell-temperature-and-filovirus-filament-length-explain-the-emergence-of-ebola-virus-in-mammals-predictions-of-a-thermodynamic-model
#11
P Gale
The host reservoir of Zaire ebolavirus (EBOV) remains elusive. One suggestion is that EBOV emerges in mammals when the precursor virus jumps from mayflies (or other riverine insects) to insectivorous bats. However, this does not fit with the current view that filoviruses cannot infect arthropods. Here, it is first argued that the evidence that arthropods are refractory is not definitive. Second, it is proposed that a combination of filovirus filament length and the high temperature (~42°C) experienced by an insect virus ingested by a flying bat, together with the large number of insects eaten by bats (e...
September 26, 2016: Transboundary and Emerging Diseases
https://www.readbyqxmd.com/read/27660213/viral-diversity-prey-preference-and-bartonella-prevalence-in-desmodus-rotundus-in-guatemala
#12
Amy K Wray, Kevin J Olival, David Morán, Maria Renee Lopez, Danilo Alvarez, Isamara Navarrete-Macias, Eliza Liang, Nancy B Simmons, W Ian Lipkin, Peter Daszak, Simon J Anthony
Certain bat species serve as natural reservoirs for pathogens in several key viral families including henipa-, lyssa-, corona-, and filoviruses, which may pose serious threats to human health. The Common Vampire Bat (Desmodus rotundus), due to its abundance, sanguivorous feeding habit involving humans and domestic animals, and highly social behavioral ecology, may have an unusually high potential for interspecies disease transmission. Previous studies have investigated rabies dynamics in D. rotundus, yet the diversity of other viruses, bacteria, and other microbes that these bats may carry remains largely unknown...
September 22, 2016: EcoHealth
https://www.readbyqxmd.com/read/27640102/filovirus-proteins-for-antiviral-drug-discovery-a-structure-function-analysis-of-surface-glycoproteins-and-virus-entry
#13
Baptiste Martin, Thomas Hoenen, Bruno Canard, Etienne Decroly
This review focuses on the recent progress in our understanding of filovirus protein structure/function and its impact on antiviral research. Here we focus on the surface glycoprotein GP1,2 and its different roles in filovirus entry. We first describe the latest advances on the characterization of GP gene-overlapping proteins sGP, ssGP and Δ-peptide. Then, we compare filovirus surface GP1,2 proteins in terms of structure, synthesis and function. As they bear potential in drug-design, the discovery of small organic compounds inhibiting filovirus entry is a currently very active field...
September 14, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27638946/analysis-of-diagnostic-findings-from-the-european-mobile-laboratory-in-gu%C3%A3-ck%C3%A3-dou-guinea-march-2014-through-march-2015
#14
Romy Kerber, Ralf Krumkamp, Boubacar Diallo, Anna Jaeger, Martin Rudolf, Simone Lanini, Joseph Akoi Bore, Fara Raymond Koundouno, Beate Becker-Ziaja, Erna Fleischmann, Kilian Stoecker, Silvia Meschi, Stéphane Mély, Edmund N C Newman, Fabrizio Carletti, Jasmine Portmann, Misa Korva, Svenja Wolff, Peter Molkenthin, Zoltan Kis, Anne Kelterbaum, Anne Bocquin, Thomas Strecker, Alexandra Fizet, Concetta Castilletti, Gordian Schudt, Lisa Ottowell, Andreas Kurth, Barry Atkinson, Marlis Badusche, Angela Cannas, Elisa Pallasch, Andrew Bosworth, Constanze Yue, Bernadett Pályi, Heinz Ellerbrok, Claudia Kohl, Lisa Oestereich, Christopher H Logue, Anja Lüdtke, Martin Richter, Didier Ngabo, Benny Borremans, Dirk Becker, Sophie Gryseels, Saïd Abdellati, Tine Vermoesen, Eeva Kuisma, Annette Kraus, Britta Liedigk, Piet Maes, Ruth Thom, Sophie Duraffour, Sandra Diederich, Julia Hinzmann, Babak Afrough, Johanna Repits, Marc Mertens, Inês Vitoriano, Amadou Bah, Andreas Sachse, Jan Peter Boettcher, Stephanie Wurr, Sabrina Bockholt, Andreas Nitsche, Tatjana Avšič Županc, Marc Strasser, Giuseppe Ippolito, Stephan Becker, Herve Raoul, Miles W Carroll, Hilde De Clerck, Michel Van Herp, Armand Sprecher, Lamine Koivogui, N'Faly Magassouba, Sakoba Keïta, Patrick Drury, Cèline Gurry, Pierre Formenty, Jürgen May, Martin Gabriel, Roman Wölfel, Stephan Günther, Antonino Di Caro
BACKGROUND:  A unit of the European Mobile Laboratory (EMLab) consortium was deployed to the Ebola virus disease (EVD) treatment unit in Guéckédou, Guinea, from March 2014 through March 2015. METHODS:  The unit diagnosed EVD and malaria, using the RealStar Filovirus Screen reverse transcription-polymerase chain reaction (RT-PCR) kit and a malaria rapid diagnostic test, respectively. RESULTS:  The cleaned EMLab database comprised 4719 samples from 2741 cases of suspected EVD from Guinea...
October 15, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27608667/a-trojan-horse-bispecific-antibody-strategy-for-broad-protection-against-ebolaviruses
#15
Anna Z Wec, Elisabeth K Nyakatura, Andrew S Herbert, Katie A Howell, Frederick W Holtsberg, Russell R Bakken, Eva Mittler, John R Christin, Sergey Shulenin, Rohit K Jangra, Sushma Bharrhan, Ana I Kuehne, Zachary A Bornholdt, Andrew I Flyak, Erica Ollmann Saphire, James E Crowe, M Javad Aman, John M Dye, Jonathan R Lai, Kartik Chandran
There is an urgent need for monoclonal antibody (mAb) therapies that broadly protect against Ebola virus and other filoviruses. The conserved, essential interaction between the filovirus glycoprotein, GP, and its entry receptor Niemann-Pick C1 (NPC1) provides an attractive target for such mAbs but is shielded by multiple mechanisms, including physical sequestration in late endosomes. Here, we describe a bispecific-antibody strategy to target this interaction, in which mAbs specific for NPC1 or the GP receptor-binding site are coupled to a mAb against a conserved, surface-exposed GP epitope...
October 21, 2016: Science
https://www.readbyqxmd.com/read/27587635/the-epi-info-viral-hemorrhagic-fever-vhf-application-a-resource-for-outbreak-data-management-and-contact-tracing-in-the-2014-2016-west-africa-ebola-epidemic
#16
Ilana J Schafer, Erik Knudsen, Lucy A McNamara, Sachin Agnihotri, Pierre E Rollin, Asad Islam
The Epi Info Viral Hemorrhagic Fever application (Epi Info VHF) was developed in response to challenges managing outbreak data during four 2012 filovirus outbreaks. Development goals included combining case and contact data in a relational database, facilitating data-driven contact tracing, and improving outbreak data consistency and use. The application was first deployed in Guinea, when the West Africa Ebola epidemic was detected, in March 2014, and has been used in 7 African countries and 2 US states. Epi Info VHF enabled reporting of compatible data from multiple countries, contributing to international Ebola knowledge...
October 15, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27581733/suramin-is-a-potent-inhibitor-of-chikungunya-and-ebola-virus-cell-entry
#17
Lisa Henß, Simon Beck, Tatjana Weidner, Nadine Biedenkopf, Katja Sliva, Christopher Weber, Stephan Becker, Barbara S Schnierle
BACKGROUND: Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes high fever, rash, and recurrent arthritis in humans. It has efficiently adapted to Aedes albopictus, which also inhabits temperate regions and currently causes large outbreaks in the Caribbean and Latin America. Ebola virus (EBOV) is a member of the filovirus family. It causes the Ebola virus disease (EDV), formerly known as Ebola hemorrhagic fever in humans and has a mortality rate of up to 70 %. The last outbreak in Western Africa was the largest in history and has caused approximately 25,000 cases and 10,000 deaths...
August 31, 2016: Virology Journal
https://www.readbyqxmd.com/read/27549586/evaluation-of-realstar-reverse-transcription-polymerase-chain-reaction-kits-for-filovirus-detection-in-the-laboratory-and-field
#18
Toni Rieger, Romy Kerber, Hussein El Halas, Elisa Pallasch, Sophie Duraffour, Stephan Günther, Stephan Ölschläger
BACKGROUND:  Diagnosis of Ebola virus (EBOV) disease (EVD) requires laboratory testing. METHODS:  The RealStar Filovirus Screen reverse transcription-polymerase chain reaction (RT-PCR) kit and the derived RealStar Zaire Ebolavirus RT-PCR kit were validated using in vitro transcripts, supernatant of infected cell cultures, and clinical specimens from patients with EVD. RESULTS:  The Filovirus Screen kit detected EBOV, Sudan virus, Taï Forest virus, Bundibugyo virus, Reston virus, and Marburg virus and differentiated between the genera Ebolavirus and Marburgvirus The amount of filovirus RNA that could be detected with a probability of 95% ranged from 11 to 67 RNA copies/reaction on a LightCycler 480 II...
October 15, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27512112/positive-selection-drives-evolution-at-the-host-filovirus-interaction-surface
#19
Chiara Pontremoli, Diego Forni, Rachele Cagliani, Giulia Filippi, Luca De Gioia, Uberto Pozzoli, Mario Clerici, Manuela Sironi
Filovirus infection is mediated by engagement of the surface-exposed glycoprotein (GP) by its cellular receptor, NPC1 (Niemann-Pick C1). Two loops in the C domain of NPC1 (NPC1-C) bind filovirus GP. Herein, we show that filovirus GP and NPC1-C evolve under mutual selective pressure. Analysis of a large mammalian phylogeny indicated that strong functional/structural constraints limit the NPC1 sequence space available for adaptive change and most sites at the contact interface with GP are under negative selection...
November 2016: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/27490565/clomiphene-and-its-isomers-block-ebola-virus-particle-entry-and-infection-with-similar-potency-potential-therapeutic-implications
#20
Elizabeth A Nelson, Alyson B Barnes, Ronald D Wiehle, Gregory K Fontenot, Thomas Hoenen, Judith M White
The 2014 outbreak of Ebola virus (EBOV) in Western Africa highlighted the need for anti-EBOV therapeutics. Clomiphene is a U.S. Food and Drug Administration (FDA)-approved drug that blocks EBOV entry and infection in cells and significantly protects EBOV-challenged mice. As provided, clomiphene is, approximately, a 60:40 mixture of two stereoisomers, enclomiphene and zuclomiphene. The pharmacokinetic properties of the two isomers vary, but both accumulate in the eye and male reproductive tract, tissues in which EBOV can persist...
2016: Viruses
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