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https://www.readbyqxmd.com/read/28525755/antibodies-from-a-human-survivor-define-sites-of-vulnerability-for-broad-protection-against-ebolaviruses
#1
Anna Z Wec, Andrew S Herbert, Charles D Murin, Elisabeth K Nyakatura, Dafna M Abelson, J Maximilian Fels, Shihua He, Rebekah M James, Marc-Antoine de La Vega, Wenjun Zhu, Russell R Bakken, Eileen Goodwin, Hannah L Turner, Rohit K Jangra, Larry Zeitlin, Xiangguo Qiu, Jonathan R Lai, Laura M Walker, Andrew B Ward, John M Dye, Kartik Chandran, Zachary A Bornholdt
Experimental monoclonal antibody (mAb) therapies have shown promise for treatment of lethal Ebola virus (EBOV) infections, but their species-specific recognition of the viral glycoprotein (GP) has limited their use against other divergent ebolaviruses associated with human disease. Here, we mined the human immune response to natural EBOV infection and identified mAbs with exceptionally potent pan-ebolavirus neutralizing activity and protective efficacy against three virulent ebolaviruses. These mAbs recognize an inter-protomer epitope in the GP fusion loop, a critical and conserved element of the viral membrane fusion machinery, and neutralize viral entry by targeting a proteolytically primed, fusion-competent GP intermediate (GPCL) generated in host cell endosomes...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28508220/reverse-genetics-systems-for-filoviruses
#2
Thomas Hoenen, Heinz Feldmann
Filoviruses are among the most pathogenic viruses known to man. Reverse genetics systems, in particular full-length clone systems, allow the generation of recombinant filoviruses, which can be used to study virus biology, but also for applied uses such as screening for countermeasures. Here we describe the generation of recombinant filoviruses from cDNA.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28505570/clinical-evaluation-of-the-biofire-filmarray-%C3%A2-biothreat-e-test-for-the-diagnosis-of-ebola-virus-disease-in-guinea
#3
Françoise Gay-Andrieu, N'Fally Magassouba, Valentina Picot, Cynthia L Phillips, Christophe N Peyrefitte, Brigitte Dacosta, Ahmadou Doré, Fode Kourouma, Véronique Ligeon-Ligeonnet, Corentin Gauby, Christophe Longuet, Matt Scullion, Ousmane Faye, Jean Louis Machuron, Mark Miller
BACKGROUND: The recent West Africa Ebola outbreak highlighted the need to provide access to rapid, safe and reliable Ebola Virus Disease diagnostics. OBJECTIVES: The objective of this field study was to assess the clinical performance of the FilmArray(®) BioThreat-E test for the detection of Ebola Zaïre virus in whole blood in symptomatic patients suspected of Ebola Virus Disease in Conakry (Guinea) from March to July 2015. STUDY DESIGN: The BioThreat-E test was compared to the two RT-PCRs, using serum, implemented at Donka Hospital in the emergency context: an in-house developed quantitative one-step RT-PCR adapted from the Weidmann technique, and the RealStar(®) Filovirus RT-PCR Kit 1...
May 1, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28465098/flex-nucleoside-analogues-novel-therapeutics-against-filoviruses
#4
Mary K Yates, Mithun R Raje, Payel Chatterjee, Christina F Spiropoulou, Sina Bavari, Mike Flint, Veronica Soloveva, Katherine L Seley-Radtke
Fleximers, a novel type of flexible nucleoside that have garnered attention due to their unprecedented activity against human coronaviruses, have now exhibited highly promising levels of activity against filoviruses. The Flex-nucleoside was the most potent against recombinant Ebola virus in Huh7 cells with an EC50=2μM, while the McGuigan prodrug was most active against Sudan virus-infected HeLa cells with an EC50 of 7μM.
April 22, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28447193/ebola-and-marburg-virus-vaccines
#5
REVIEW
Pierce Reynolds, Andrea Marzi
The filoviruses, Ebola virus (EBOV), and Marburg virus (MARV), are among the most pathogenic viruses known to man and the causative agents of viral hemorrhagic fever outbreaks in Africa with case fatality rates of up to 90%. Nearly 30,000 infections were observed in the latest EBOV epidemic in West Africa; previous outbreaks were much smaller, typically only affecting less than a few hundred people. Compared to other diseases such as AIDS or Malaria with millions of cases annually, filovirus hemorrhagic fever (FHF) is one of the neglected infectious diseases...
April 26, 2017: Virus Genes
https://www.readbyqxmd.com/read/28442605/the-toll-like-receptor-4-antagonist-eritoran-protects-mice-from-lethal-filovirus-challenge
#6
Patrick Younan, Palaniappan Ramanathan, Jessica Graber, Fabian Gusovsky, Alexander Bukreyev
The 2013-2016 outbreak of Ebola virus (EBOV) in West Africa, which has seen intermittent reemergence since it was officially declared over in February of 2016, has demonstrated the need for the rapid development of therapeutic intervention strategies. Indirect evidence has suggested that the EBOV infection shares several commonalities associated with the onset of bacterial sepsis, including the development of a "cytokine storm." Eritoran, a Toll-like receptor 4 (TLR4) antagonist, was previously shown to result in protection of mice against lethal influenza virus infection...
April 25, 2017: MBio
https://www.readbyqxmd.com/read/28418192/detection-of-potentially-novel-paramyxovirus-and-coronavirus-viral-rna-in-bats-and-rats-in-the-mekong-delta-region-of-southern-viet-nam
#7
A Berto, P H Anh, J J Carrique-Mas, P Simmonds, N Van Cuong, N T Tue, N Van Dung, M E Woolhouse, I Smith, G A Marsh, J E Bryant, G E Thwaites, S Baker, M A Rabaa
Bats and rodents are being increasingly recognized as reservoirs of emerging zoonotic viruses. Various studies have investigated bat viruses in tropical regions, but to date there are no data regarding viruses with zoonotic potential that circulate in bat and rat populations in Viet Nam. To address this paucity of data, we sampled three bat farms and three wet markets trading in rat meat in the Mekong Delta region of southern Viet Nam. Faecal and urine samples were screened for the presence of RNA from paramyxoviruses, coronaviruses and filoviruses...
April 18, 2017: Zoonoses and Public Health
https://www.readbyqxmd.com/read/28393313/molecular-detection-of-viruses-in-kenyan-bats-and-discovery-of-novel-astroviruses-caliciviruses-and-rotaviruses
#8
Cecilia Waruhiu, Sheila Ommeh, Vincent Obanda, Bernard Agwanda, Francis Gakuya, Xing-Yi Ge, Xing-Lou Yang, Li-Jun Wu, Ali Zohaib, Ben Hu, Zheng-Li Shi
This is the first country-wide surveillance of bat-borne viruses in Kenya spanning from 2012-2015 covering sites perceived to have medium to high level bat-human interaction. The objective of this surveillance study was to apply a non-invasive approach using fresh feces to detect viruses circulating within the diverse species of Kenyan bats. We screened for both DNA and RNA viruses; specifically, astroviruses (AstVs), adenoviruses (ADVs), caliciviruses (CalVs), coronaviruses (CoVs), flaviviruses, filoviruses, paramyxoviruses (PMVs), polyomaviruses (PYVs) and rotaviruses...
April 6, 2017: Virologica Sinica
https://www.readbyqxmd.com/read/28385983/fighting-filoviruses-with-antibody-therapy
#9
EDITORIAL
Lindsey Pujanandez
No abstract text is available yet for this article.
April 7, 2017: Science
https://www.readbyqxmd.com/read/28381540/therapeutic-treatment-of-marburg-and-ravn-virus-infection-in-nonhuman-primates-with-a-human-monoclonal-antibody
#10
Chad E Mire, Joan B Geisbert, Viktoriya Borisevich, Karla A Fenton, Krystle N Agans, Andrew I Flyak, Daniel J Deer, Herta Steinkellner, Ognian Bohorov, Natasha Bohorova, Charles Goodman, Andrew Hiatt, Do H Kim, Michael H Pauly, Jesus Velasco, Kevin J Whaley, James E Crowe, Larry Zeitlin, Thomas W Geisbert
As observed during the 2013-2016 Ebola virus disease epidemic, containment of filovirus outbreaks is challenging and made more difficult by the lack of approved vaccine or therapeutic options. Marburg and Ravn viruses are highly virulent and cause severe and frequently lethal disease in humans. Monoclonal antibodies (mAbs) are a platform technology in wide use for autoimmune and oncology indications. Previously, we described human mAbs that can protect mice from lethal challenge with Marburg virus. We demonstrate that one of these mAbs, MR191-N, can confer a survival benefit of up to 100% to Marburg or Ravn virus-infected rhesus macaques when treatment is initiated up to 5 days post-inoculation...
April 5, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28331098/recombinant-modified-vaccinia-virus-ankara-generating-ebola-virus-like-particles
#11
Marc Schweneker, Andrea S Laimbacher, Gert Zimmer, Susanne Wagner, Elisabeth M Schraner, Michael Wolferstätter, Marieken Klingenberg, Ulrike Dirmeier, Robin Steigerwald, Henning Lauterbach, Hubertus Hochrein, Paul Chaplin, Mark Suter, Jürgen Hausmann
There are currently no approved therapeutics or vaccines to treat or protect against the severe hemorrhagic fever and death caused by Ebola virus (EBOV). Ebola virus-like particles (EBOV-VLPs) consisting of the matrix protein VP40, the glycoprotein (GP) and the nucleoprotein (NP) are highly immunogenic and protective in non-human primates against Ebola virus disease (EVD). We have constructed a modified vaccinia virus Ankara-Bavarian Nordic(®) (MVA-BN(®)) recombinant co-expressing VP40 and glycoprotein (GP) of EBOV Mayinga and the nucleoprotein (NP) of Taï Forest virus (TAFV) (MVA-BN-EBOV-VLP) to launch non-infectious EBOV-VLPs as a second vaccine modality in the MVA-BN-EBOV-VLP-vaccinated organism...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28221123/genetically-diverse-filoviruses-in-rousettus-and-eonycteris-spp-bats-china-2009-and-2015
#12
Xing-Lou Yang, Yun-Zhi Zhang, Ren-Di Jiang, Hua Guo, Wei Zhang, Bei Li, Ning Wang, Li Wang, Cecilia Waruhiu, Ji-Hua Zhou, Shi-Yue Li, Peter Daszak, Lin-Fa Wang, Zheng-Li Shi
Genetically divergent filoviruses detected in Rousettus and Eonycteris spp. bats in China exhibited 61%-99% nt identity with reported filoviruses, based on partial replicase sequences, and they demonstrated lung tropism. Co-infection with 4 different filoviruses was found in 1 bat. These results demonstrate that fruit bats are key reservoirs of filoviruses.
March 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28216187/recombinant-proteins-of-zaire-ebolavirus-induce-potent-humoral-and-cellular-immune-responses-and-protect-against-live-virus-infection-in-mice
#13
Axel T Lehrer, Teri-Ann S Wong, Michael M Lieberman, Tom Humphreys, David E Clements, Russell R Bakken, Mary Kate Hart, William D Pratt, John M Dye
Infections with filoviruses in humans are highly virulent, causing hemorrhagic fevers which result in up to 90% mortality. In addition to natural infections, the ability to use these viruses as bioterrorist weapons is of significant concern. Currently, there are no licensed vaccines or therapeutics available to combat these infections. The pathogenesis of disease involves the dysregulation of the host's immune system, which results in impairment of the innate and adaptive immune responses, with subsequent development of lymphopenia, thrombocytopenia, hemorrhage, and death...
February 16, 2017: Vaccine
https://www.readbyqxmd.com/read/28197923/viral-interplay-with-the-host-sumoylation-system
#14
Van G Wilson
Viruses have evolved elaborate means to regulate diverse cellular pathways in order to create a cellular environment that facilitates viral survival and reproduction. This includes enhancing viral macromolecular synthesis and assembly, as well as preventing antiviral responses, including intrinsic, innate, and adaptive immunity. There are numerous mechanisms by which viruses mediate their effects on the host cell, and this includes targeting various cellular post-translational modification systems, including sumoylation...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28194016/modelling-filovirus-maintenance-in-nature-by-experimental-transmission-of-marburg-virus-between-egyptian-rousette-bats
#15
Amy J Schuh, Brian R Amman, Megan E B Jones, Tara K Sealy, Luke S Uebelhoer, Jessica R Spengler, Brock E Martin, Jo Ann D Coleman-McCray, Stuart T Nichol, Jonathan S Towner
The Egyptian rousette bat (ERB) is a natural reservoir host for Marburg virus (MARV); however, the mechanisms by which MARV is transmitted bat-to-bat and to other animals are unclear. Here we co-house MARV-inoculated donor ERBs with naive contact ERBs. MARV shedding is detected in oral, rectal and urine specimens from inoculated bats from 5-19 days post infection. Simultaneously, MARV is detected in oral specimens from contact bats, indicating oral exposure to the virus. In the late study phase, we provide evidence that MARV can be horizontally transmitted from inoculated to contact ERBs by finding MARV RNA in blood and oral specimens from contact bats, followed by MARV IgG antibodies in these same bats...
February 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28192094/filovirus-proteins-for-antiviral-drug-discovery-structure-function-bases-of-the-replication-cycle
#16
REVIEW
Baptiste Martin, Bruno Canard, Etienne Decroly
Filoviruses are important pathogens that cause severe and often fatal hemorrhagic fever in humans, for which no approved vaccines and antiviral treatments are yet available. In an earlier article (Martin et al., Antiviral Research, 2016), we reviewed the role of the filovirus surface glycoprotein in replication and as a target for drugs and vaccines. In this review, we focus on recent findings on the filovirus replication machinery and how they could be used for the identification of new therapeutic targets and the development of new antiviral compounds...
February 10, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28152588/a-sensitive-in-vitro-high-throughput-screen-to-identify-pan-filoviral-replication-inhibitors-targeting-the-vp35-np-interface
#17
Gai Liu, Peter J Nash, Britney Johnson, Colette Pietzsch, Ma Xenia G Ilagan, Alexander Bukreyev, Christopher F Basler, Terry L Bowlin, Donald T Moir, Daisy W Leung, Gaya K Amarasinghe
The 2014 Ebola outbreak in West Africa, the largest outbreak on record, highlighted the need for novel approaches to therapeutics targeting Ebola virus (EBOV). Within the EBOV replication complex, the interaction between polymerase cofactor, viral protein 35 (VP35), and nucleoprotein (NP) is critical for viral RNA synthesis. We recently identified a peptide at the N-terminus of VP35 (termed NPBP) that is sufficient for interaction with NP and suppresses EBOV replication, suggesting that the NPBP binding pocket can serve as a potential drug target...
March 10, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28122983/innate-immune-responses-of-bat-and-human-cells-to-filoviruses-commonalities-and-distinctions
#18
Ivan V Kuzmin, Toni M Schwarz, Philipp A Ilinykh, Ingo Jordan, Thomas G Ksiazek, Ravi Sachidanandam, Christopher F Basler, Alexander Bukreyev
Marburg (MARV) and Ebola (EBOV) viruses are zoonotic pathogens that cause severe hemorrhagic fever in humans. The natural reservoir of MARV is the Egyptian rousette bat (Rousettus aegyptiacus); that of EBOV is unknown but believed to be another bat species. The Egyptian rousette develops subclinical productive infection with MARV but is refractory to EBOV. Interaction of filoviruses with hosts is greatly affected by the viral interferon (IFN)-inhibiting domains (IID). Our study was aimed at characterization of innate immune responses to filoviruses and the role of filovirus IID in bat and human cells...
April 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28076420/chaperone-mediated-autophagy-protein-bag3-negatively-regulates-ebola-and-marburg-vp40-mediated-egress
#19
Jingjing Liang, Cari A Sagum, Mark T Bedford, Sachdev S Sidhu, Marius Sudol, Ziying Han, Ronald N Harty
Ebola (EBOV) and Marburg (MARV) viruses are members of the Filoviridae family which cause outbreaks of hemorrhagic fever. The filovirus VP40 matrix protein is essential for virus assembly and budding, and its PPxY L-domain motif interacts with WW-domains of specific host proteins, such as Nedd4 and ITCH, to facilitate the late stage of virus-cell separation. To identify additional WW-domain-bearing host proteins that interact with VP40, we used an EBOV PPxY-containing peptide to screen an array of 115 mammalian WW-domain-bearing proteins...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28012412/human-transmission-of-ebola-virus
#20
REVIEW
Philip Lawrence, Nicolas Danet, Olivier Reynard, Valentina Volchkova, Viktor Volchkov
Ever since the first recognised outbreak of Ebolavirus in 1976, retrospective epidemiological analyses and extensive studies with animal models have given us insight into the nature of the pathology and transmission mechanisms of this virus. In this review focusing on Ebolavirus, we present an outline of our current understanding of filovirus human-to-human transmission and of our knowledge concerning the molecular basis of viral transmission and potential for adaptation, with particular focus on what we have learnt from the 2014 outbreak in West Africa...
December 21, 2016: Current Opinion in Virology
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