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Mohan Natesan, Sz-Wei Wu, Chieh-I Chen, Stig Mr Jensen, Neven Karlovac, Beverly K Dyas, Onur Mudanyali, Robert G Ulrich
We have developed a digital and multiplexed platform for the rapid detection and telemonitoring of infections caused by Ebola and Marburg filoviruses. The system includes a flow cell assay cartridge that captures specific antibodies with microarrayed recombinant antigens from all six species of filovirus, and a smartphone fluorescent reader for high-performance interpretation of test results. Multiplexed viral proteins, which are expandable to include greater numbers of probes, were incorporated to obtain highest confidence results by cross-correlation, and custom smartphone application was developed for data analysis, interpretation and communication...
December 7, 2018: ACS Sensors
Greg Fedewa, Sheli R Radoshitzky, Xiǎolì Chī, Lián Dǒng, Xiankun Zeng, Melissa Spear, Nicolas Strauli, Melinda Ng, Kartik Chandran, Mark D Stenglein, Ryan D Hernandez, Peter B Jahrling, Jens H Kuhn, Joseph L DeRisi
Ebola virus (EBOV) disease is a viral hemorrhagic fever with a high case-fatality rate in humans. This disease is caused by four members of the filoviral genus Ebolavirus , including EBOV. The natural hosts reservoirs of ebolaviruses remain to be identified. Glycoprotein 2 of reptarenaviruses, known to infect only boa constrictors and pythons, is similar in sequence and structure to ebolaviral glycoprotein 2, suggesting that EBOV may be able to infect reptilian cells. Therefore, we serially passaged EBOV and a distantly related filovirus, Marburg virus (MARV), in boa constrictor JK cells and characterized viral infection/replication and mutational frequency by confocal imaging and sequencing...
July 2018: Virus Evolution
Ping Cao, Haihong Bai, Xinghe Wang, Jinjing Che
MIL77, which has a higher manufacturing capacity than ZMapp, comprises MIL77-1, MIL77-2, and MIL77-3. The mechanisms by which these antibodies inhibit glycoprotein are unclear. Infection by viruses with lipid-bilayer envelopes occurs via the fusion of the viral membrane with the membrane of the target cell. Therefore, the interaction between the antibodies and the EBOV membrane is crucial. We examined the interactions between MIL77 and the viral membrane using SPR. MIL77-1 selectively binds to viral membranes, while MIL77-2 and MIL77-3 do not...
December 4, 2018: Scientific Reports
Brayden G Schindell, Andrew L Webb, Jason Kindrachuk
There is an increasing frequency of reports regarding the persistence of the Ebola virus (EBOV) in Ebola virus disease (EVD) survivors. During the 2014⁻2016 West African EVD epidemic, sporadic transmission events resulted in the initiation of new chains of human-to-human transmission. Multiple reports strongly suggest that these re-emergences were linked to persistent EBOV infections and included sexual transmission from EVD survivors. Asymptomatic infection and long-term viral persistence in EVD survivors could result in incidental introductions of the Ebola virus in new geographic regions and raise important national and local public health concerns...
December 2, 2018: Viruses
Qinghua Cui, Han Cheng, Rui Xiong, Gang Zhang, Ruikun Du, Manu Anantpadma, Robert A Davey, Lijun Rong
Ebola virus is the causative agent of Ebola virus disease in humans. The lethality of Ebola virus infection is about 50%, supporting the urgent need to develop anti-Ebola drugs. Glycoprotein (GP) is the only surface protein of the Ebola virus, which is functionally critical for the virus to attach and enter the host cells, and is a promising target for anti-Ebola virus drug development. In this study, using the recombinant HIV-1/Ebola pseudovirus platform we previously established, we evaluated a small molecule library containing various quinoline compounds for anti-Ebola virus entry inhibitors...
November 30, 2018: Viruses
Saskia Den Boon, Barbara J Marston, Tolbert G Nyenswah, Amara Jambai, Moumie Barry, Sakoba Keita, Kara Durski, Schabbethai S Senesie, Devin Perkins, Anita Shah, Hugh H Green, Esther L Hamblion, Margaret Lamunu, Alex Gasasira, Nuha O Mahmoud, Mamadou H Djingarey, Oliver Morgan, Ian Crozier, Christopher Dye
Ebola virus (EBOV) can persist in immunologically protected body sites in survivors of Ebola virus disease, creating the potential to initiate new chains of transmission. From the outbreak in West Africa during 2014-2016, we identified 13 possible events of viral persistence-derived transmission of EBOV (VPDTe) and applied predefined criteria to classify transmission events based on the strength of evidence for VPDTe and source and route of transmission. For 8 events, a recipient case was identified; possible source cases were identified for 5 of these 8...
February 17, 2019: Emerging Infectious Diseases
Dong-Shan Yu, Tian-Hao Weng, Chen-Yu Hu, Zhi-Gang Wu, Yan-Hua Li, Lin-Fang Cheng, Nan-Ping Wu, Lan-Juan Li, Hang-Ping Yao
Ebolavirus (EBOV) life cycle involves interactions with numerous host factors, but it remains poorly understood, as does pathogenesis. Herein, we synthesized 65 siRNAs targeting host genes mostly connected with aspects of the negative-sense RNA virus life cycle (including viral entry, uncoating, fusion, replication, assembly, and budding). We produced EBOV transcription- and replication-competent virus-like particles (trVLPs) to mimic the EBOV life cycle. After screening host factors associated with the trVLP life cycle, we assessed interactions of host proteins with trVLP glycoprotein (GP), VP40, and RNA by co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (ChIP)...
2018: Frontiers in Microbiology
Luca Zinzula, István Nagy, Massimiliano Orsini, Elisabeth Weyher-Stingl, Andreas Bracher, Wolfgang Baumeister
The multifunctional virion protein 35 (VP35) of ebolaviruses is a critical determinant of virulence and pathogenesis indispensable for viral replication and host innate immune evasion. Essential for VP35 function is homo-oligomerization via a coiled-coil motif. Here we report crystal structures of VP35 oligomerization domains from the prototypic Ebola virus (EBOV) and the non-pathogenic Reston virus (RESTV), together with a comparative biophysical characterization of the domains from all known species of the Ebolavirus genus...
October 5, 2018: Structure
Joseph D Bazzill, Sabrina M Stronsky, Laura C Kalinyak, Lukasz J Ochyl, Jesse T Steffens, Sean A van Tongeren, Christopher L Cooper, James J Moon
The recent outbreaks of Ebolavirus (EBOV) in West Africa underscore the urgent need to develop an effective EBOV vaccine. Here, we report the development of synthetic nanoparticles as a safe and highly immunogenic platform for vaccination against EBOV. We show that a large recombinant EBOV antigen (rGP) can be incorporated in a configurational manner into lipid-based nanoparticles, termed interbilayer-crosslinked multilamellar vesicles (ICMVs). The epitopes and quaternary structure of rGP were properly maintained on the surfaces of ICMVs formed either with or without nickel nitrilotriacetic acid (NTA)-functionalized lipids...
November 21, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
Elisa Fanunza, Aldo Frau, Angela Corona, Enzo Tramontano
Upon viral infection, the interferon (IFN) system triggers potent antiviral mechanisms limiting viral growth and spread. Hence, to sustain their infection, viruses evolved efficient counteracting strategies to evade IFN control. Ebola virus (EBOV), member of the family Filoviridae, is one of the most virulent and deadly pathogen ever faced by humans. Etiological agent of the Ebola virus disease (EVD), EBOV can be undoubtedly considered the perfect example of a powerful inhibitor of the host organism immune response activation...
November 23, 2018: Infectious Disorders Drug Targets
Mochammad Arfin Fardiansyah Nasution, Erwin Prasetya Toepak, Ahmad Husein Alkaff, Usman Sumo Friend Tambunan
BACKGROUND: Ebola still remains as one of the most problematic infectious diseases in Africa with a high rate of mortality. Although this disease has been known for an almost half-century, there are no vaccines and drugs available in the market to treat Ebola. Zaire ebolavirus (EBOV), a single-stranded RNA virus which belongs to Filoviridae family and Mononegavirales order, is one of the virus causing Ebola. As one of seven proteins that EBOV encodes, Ebola virus nucleoprotein (EBOV NP) plays an imperative role in EBOV proliferation cycle...
November 20, 2018: BMC Bioinformatics
Kendra J Alfson, Laura E Avena, Michael W Beadles, Gabriella Worwa, Melanie Amen, Jean L Patterson, Ricardo Carrion, Anthony Griffiths
The filoviruses Ebola virus (EBOV) and Sudan virus (SUDV) can cause severe diseases, and there are currently no licensed countermeasures available for use against them. Transmission occurs frequently via contact with bodily fluids from infected individuals. However, it can be difficult to determine when or how someone became infected, or the quantity of infectious virus to which they were exposed. Evidence suggests the infectious dose is low, but the majority of published studies use high exposure doses. This study characterized the outcome of exposure to a low dose of EBOV or SUDV, using a Macaca fascicularis model...
November 16, 2018: Viruses
Joseph H Poetsch, Christine Dahlke, Madeleine E Zinser, Rahel Kasonta, Sebastian Lunemann, Anne Rechtien, My L Ly, Hans C Stubbe, Verena Krähling, Nadine Biedenkopf, Markus Eickmann, Sarah K Fehling, Flaminia Olearo, Thomas Strecker, Piyush Sharma, Karl S Lang, Ansgar W Lohse, Stefan Schmiedel, Stephan Becker, Marylyn M Addo
In response to the Ebola virus (EBOV) crisis of 2013-2016, a recombinant vesicular stomatitis virus (VSV)-based EBOV vaccine was clinically tested (NCT02283099). A single-dose regimen of VSV-EBOV revealed a safe and immunogenic profile and demonstrated clinical efficacy. While EBOV-specific immune responses to this candidate vaccine have previously been investigated, limited human data on immunity to the VSV vector are available. Within the scope of a phase 1 study, we performed a comprehensive longitudinal analysis of adaptive immune responses to internal VSV proteins following VSV-EBOV immunization...
November 17, 2018: Journal of Infectious Diseases
Markus Hoffmann, Inga Nehlmeier, Constantin Brinkmann, Verena Krähling, Laura Behner, Anna-Sophie Moldenhauer, Nadine Krüger, Julia Nehls, Michael Schindler, Thomas Hoenen, Andrea Maisner, Stephan Becker, Stefan Pöhlmann
Ebola virus (EBOV) and Nipah virus (NiV) infection of humans can cause fatal disease and constitutes a public health threat. In contrast, EBOV and NiV infection of fruit bats, the putative (EBOV) or proven (NiV) natural reservoir, is not associated with disease and it is currently unknown how these animals control the virus. The human interferon (IFN)-stimulated antiviral effector protein tetherin (CD317, BST-2) blocks release of EBOV- and NiV-like particles from cells and is counteracted by the EBOV glycoprotein (GP)...
November 14, 2018: Journal of Virology
Ami Patel, Daniel H Park, Carl W Davis, Trevor R F Smith, Anders Leung, Kevin Tierney, Aubrey Bryan, Edgar Davidson, Xiaoying Yu, Trina Racine, Charles Reed, Marguerite E Gorman, Megan C Wise, Sarah T C Elliott, Rianne Esquivel, Jian Yan, Jing Chen, Kar Muthumani, Benjamin J Doranz, Erica Ollmann Saphire, James E Crowe, Kate E Broderick, Gary P Kobinger, Shihua He, Xiangguo Qiu, Darwyn Kobasa, Laurent Humeau, Niranjan Y Sardesai, Rafi Ahmed, David B Weiner
Synthetically engineered DNA-encoded monoclonal antibodies (DMAbs) are an in vivo platform for evaluation and delivery of human mAb to control against infectious disease. Here, we engineer DMAbs encoding potent anti-Zaire ebolavirus (EBOV) glycoprotein (GP) mAbs isolated from Ebola virus disease survivors. We demonstrate the development of a human IgG1 DMAb platform for in vivo EBOV-GP mAb delivery and evaluation in a mouse model. Using this approach, we show that DMAb-11 and DMAb-34 exhibit functional and molecular profiles comparable to recombinant mAb, have a wide window of expression, and provide rapid protection against lethal mouse-adapted EBOV challenge...
November 13, 2018: Cell Reports
Života Selaković, Julie P Tran, Krishna P Kota, Marija Lazić, Cary Retterer, Robert Besh, Rekha G Panchal, Veronica Soloveva, Vantongreen A Sean, Wells B Jay, Aleksandar Pavić, Tatjana Verbić, Branka Vasiljević, Kathleen Kuehl, Allen J Duplantier, Sina Bavari, Rajini Mudhasani, Bogdan A Šolaja
Ebola virus (EBOV) causes a deadly hemorrhagic fever in humans and non-human primates. There is currently no FDA-approved vaccine or medication to counter this disease. Here, we report on the design, synthesis and anti-viral activities of two classes of compounds which show high potency against EBOV in both in vitro cell culture assays and in vivo mouse models Ebola viral disease. These compounds incorporate the structural features of cationic amphiphilic drugs (CAD), i.e they possess both a hydrophobic domain and a hydrophilic domain consisting of an ionizable amine functional group...
October 31, 2018: European Journal of Medicinal Chemistry
Yu Hua Li, Ling Wang, Tao Zhu, Shipo Wu, Liqiang Feng, Ping Cheng, Jing Jing Liu, Junzhi Wang
The 2014 Ebola outbreak in West Africa had brought great threat to the public health worldwide. There were no approved anti-viral therapy and vaccine available to control the disease at that time. Several kinds of Ebola vaccines were under development urgently in the world, among which the novel recombinant adenovirus type-5 vector-based Ebola vaccine( Ad5-EBOV)-the first Ebola vaccine based on the 2014 Zaire Guinea epidemic strain was developed in China and its safety and immunogenicity were demonstrated in China and SierraLeone...
November 1, 2018: Human Gene Therapy. Clinical Development
Marc-Antoine de La Vega, Geoff Soule, Kaylie N Tran, Kevin Tierney, Shihua He, Gary Wong, Xiangguo Qiu, Gary P Kobinger
Ebola virus (EBOV) has been responsible for sporadic outbreaks in Central Africa since 1976 and has the potential of causing social disruption and public panic as illustrated by the 2013-2016 epidemic in West Africa. Transmission of EBOV has been described to occur via contact with infected bodily fluids, supported by data indicating that infectious EBOV could be cultured from blood, semen, saliva, urine, and breast milk. Parameters influencing transmission of EBOV are, however, largely undefined in part due to the lack of an established animal model to study mechanisms of pathogen spread...
October 31, 2018: MSphere
Dong-Shan Yu, Tian-Hao Weng, Ling Shen, Xiao-Xin Wu, Chen-Yu Hu, Frederick X C Wang, Zhi-Gang Wu, Hai-Bo Wu, Nan-Ping Wu, Lan-Juan Li, Hangping Yao
BACKGROUND/AIMS: Monoclonal antibodies (mAbs) are presently the most promising treatment against Ebola virus disease (EVD), and cocktail of two or more antibodies likely confers protection through complementary mechanisms. Zaire Ebolavirus (EBOV) glycoprotein (GP) and viral protein 40 (VP40) are targets for designing neutralizing antibodies. Currently, the antiviral therapeutics of mAb-cocktails are still limited solely to anti-GP antibodies,there is no Abs cocktail against Zaire EBOV GP and VP40, which both have important interactions with host cellular membrane...
2018: Cellular Physiology and Biochemistry
Gary Wong, Shihua He, Anders Leung, Wenguang Cao, Yuhai Bi, Zirui Zhang, Wenjun Zhu, Liang Wang, Yuhui Zhao, Keding Cheng, Di Liu, Wenjun Liu, Darwyn Kobasa, George F Gao, Xiangguo Qiu
Sequencing of Ebola virus (EBOV) genomes during the 2014-16 epidemic identified several naturally-occurring, dominant mutations potentially impacting virulence or tropism. Here, we characterized EBOV variants carrying one of the following substitutions: A82V in the glycoprotein (GP), R111C in the nucleoprotein (NP), or D759G in the RNA-dependent RNA-polymerase (L). Compared with wild-type EBOV/C07 (WT), NP and L mutants conferred a replication advantage in monkey VeroE6, human A549 and insectivorous bat Tb1...
October 17, 2018: Journal of Virology
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