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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
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
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
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
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
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
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
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
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
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
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...
September 8, 2016: Science
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
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
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
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
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
Robert Kozak, Shihua He, Andrea Kroeker, Marc-Antoine de La Vega, Jonathan Audet, Gary Wong, Chantel Urfano, Kym Antonation, Carissa Embury-Hyatt, Gary P Kobinger, Xiangguo Qiu
UNLABELLED: Bundibugyo virus (BDBV) is the etiological agent of a severe hemorrhagic fever in humans with a case-fatality rate ranging from 25 to 36%. Despite having been known to the scientific and medical communities for almost 1 decade, there is a dearth of studies on this pathogen due to the lack of a small animal model. Domestic ferrets are commonly used to study other RNA viruses, including members of the order Mononegavirales To investigate whether ferrets were susceptible to filovirus infections, ferrets were challenged with a clinical isolate of BDBV...
October 15, 2016: Journal of Virology
Sophie J Smither, Lin Eastaugh, Sarah Ngugi, Lyn O'Brien, Amanda Phelps, Jackie Steward, Mark Stephen Lever
Ebola virus Makona (EBOV-Makona; from the 2013-2016 West Africa outbreak) shows decreased virulence in an immune-deficient mouse model, compared with a strain from 1976. Unlike other filoviruses tested, EBOV-Makona may be slightly more virulent by the aerosol route than by the injected route, as 2 mice died following aerosol exposure, compared with no mortality among mice that received intraperitoneal injection of equivalent or higher doses. Although most mice did not succumb to infection, the detection of an immunoglobulin G antibody response along with observed clinical signs suggest that the mice were infected but able to clear the infection and recover...
October 15, 2016: Journal of Infectious Diseases
Reed F Johnson, Drishya Kurup, Katie R Hagen, Christine Fisher, Rohan Keshwara, Amy Papaneri, Donna L Perry, Kurt Cooper, Peter B Jahrling, Jonathan T Wang, Jan Ter Meulen, Christoph Wirblich, Matthias J Schnell
The 2013-2016 West African Ebola virus (EBOV) disease outbreak was the largest filovirus outbreak to date. Over 28 000 suspected, probable, or confirmed cases have been reported, with a 53% case-fatality rate. The magnitude and international impact of this EBOV outbreak has highlighted the urgent need for a safe and efficient EBOV vaccine. To this end, we demonstrate the immunogenicity and protective efficacy of FILORAB1, a recombinant, bivalent, inactivated rabies virus-based EBOV vaccine, in rhesus and cynomolgus monkeys...
October 15, 2016: Journal of Infectious Diseases
Subhajit Poddar, Jennifer L Hyde, Matthew J Gorman, Michael Farzan, Michael S Diamond
UNLABELLED: Host cells respond to viral infections by producing type I interferon (IFN), which induces the expression of hundreds of interferon-stimulated genes (ISGs). Although ISGs mediate a protective state against many pathogens, the antiviral functions of the majority of these genes have not been identified. IFITM3 is a small transmembrane ISG that restricts a broad range of viruses, including orthomyxoviruses, flaviviruses, filoviruses, and coronaviruses. Here, we show that alphavirus infection is increased in Ifitm3(-/-) and Ifitm locus deletion (Ifitm-del) fibroblasts and, reciprocally, reduced in fibroblasts transcomplemented with Ifitm3...
October 1, 2016: Journal of Virology
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