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https://www.readbyqxmd.com/read/28525756/immunization-elicited-broadly-protective-antibody-reveals-ebolavirus-fusion-loop-as-a-site-of-vulnerability
#1
Xuelian Zhao, Katie A Howell, Shihua He, Jennifer M Brannan, Anna Z Wec, Edgar Davidson, Hannah L Turner, Chi-I Chiang, Lin Lei, J Maximilian Fels, Hong Vu, Sergey Shulenin, Ashley N Turonis, Ana I Kuehne, Guodong Liu, Mi Ta, Yimeng Wang, Christopher Sundling, Yongli Xiao, Jennifer S Spence, Benjamin J Doranz, Frederick W Holtsberg, Andrew B Ward, Kartik Chandran, John M Dye, Xiangguo Qiu, Yuxing Li, M Javad Aman
While neutralizing antibodies are highly effective against ebolavirus infections, current experimental ebolavirus vaccines primarily elicit species-specific antibody responses. Here, we describe an immunization-elicited macaque antibody (CA45) that clamps the internal fusion loop with the N terminus of the ebolavirus glycoproteins (GPs) and potently neutralizes Ebola, Sudan, Bundibugyo, and Reston viruses. CA45, alone or in combination with an antibody that blocks receptor binding, provided full protection against all pathogenic ebolaviruses in mice, guinea pigs, and ferrets...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28525755/antibodies-from-a-human-survivor-define-sites-of-vulnerability-for-broad-protection-against-ebolaviruses
#2
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/28525748/ebolavirus-s-foibles
#3
Seiya Yamayoshi, Yoshihiro Kawaoka
Ebola virus disease poses a global health threat. Here, two studies by Wec et al. and Zhao et al. identified vulnerability in an internal fusion loop of an ebolavirus glycoprotein. Monoclonal antibodies elicited from immunization and isolated from a human survivor that recognized epitopes in this area neutralized all five ebolaviruses, guiding the development of a pan-ebolavirus immunotherapy.
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28523851/identification-of-multiple-druggable-secondary-sites-by-fragment-screening-against-dc-sign
#4
Jonas Aretz, Hannes Baukmann, Elena Shanina, Jonas Hanske, Robert Wawrzinek, Viktor A Zapol'skii, Peter H Seeberger, Dieter E Kaufmann, Christoph Rademacher
DC-SIGN is a cell-surface receptor for several pathogenic threats, such as HIV, Ebola virus, or Mycobacterium tuberculosis. Multiple attempts to develop inhibitors of the underlying carbohydrate-protein interactions have been undertaken in the past fifteen years. Still, drug-like DC-SIGN ligands are sparse, which is most likely due to its hydrophilic, solvent-exposed carbohydrate-binding site. Herein, we report on a parallel fragment screening against DC-SIGN applying SPR and a reporter displacement assay, which complements previous screenings using (19) F NMR spectroscopy and chemical fragment microarrays...
May 19, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28520958/the-development-use-and-impact-of-a-global-laboratory-database-during-the-2014-ebola-outbreak-in-west-africa
#5
Kara N Durski, Shalini Singaravelu, Junxiong Teo, Dhamari Naidoo, Luke Bawo, Amara Jambai, Sakoba Keita, Ali Ahmed Yahaya, Beatrice Muraguri, Brice Ahounou, Victoria Katawera, Fredson Kuti-George, Yacouba Nebie, T Henry Kohar, Patrick Jowlehpah Hardy, Mamoudou Harouna Djingarey, David Kargbo, Nuha Mahmoud, Yewondwossen Assefa, Orla Condell, Magassouba N'Faly, Leon Van Gurp, Margaret Lamanu, Julia Ryan, Boubacar Diallo, Foday Daffae, Dikena Jackson, Fayyaz Ahmed Malik, Philomena Raftery, Pierre Formenty
Background: The international impact, rapid widespread transmission, and reporting delays during the 2014 Ebola virus disease (EVD) outbreak in West Africa highlighted the need for a global, centralized database to inform outbreak response. The World Health Organization and Emerging and Dangerous Pathogens Laboratory Network addressed this need by supporting the development of a global laboratory database. Methods: Specimens were collected in the affected countries from patients and dead bodies meeting the case definitions for EVD...
May 18, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28520909/large-scale-data-driven-integrative-framework-for-extracting-essential-targets-and-processes-from-disease-associated-gene-data-sets
#6
Gaston K Mazandu, Emile R Chimusa, Kayleigh Rutherford, Elsa-Gayle Zekeng, Zoe Z Gebremariam, Maryam Y Onifade, Nicola J Mulder
Populations worldwide currently face several public health challenges, including growing prevalence of infections and the emergence of new pathogenic organisms. The cost and risk associated with drug development make the development of new drugs for several diseases, especially orphan or rare diseases, unappealing to the pharmaceutical industry. Proof of drug safety and efficacy is required before market approval, and rigorous testing makes the drug development process slow, expensive and frequently result in failure...
May 18, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28518036/sustainability-of-high-level-isolation-capabilities-among-us-ebola-treatment-centers
#7
Jocelyn J Herstein, Paul D Biddinger, Shawn G Gibbs, Aurora B Le, Katelyn C Jelden, Angela L Hewlett, John J Lowe
To identify barriers to maintaining and applying capabilities of US high-level isolation units (HLIUs) used during the Ebola virus disease outbreak, during 2016 we surveyed HLIUs. HLIUs identified sustainability challenges and reported the highly infectious diseases they would treat. HLIUs expended substantial resources in development but must strategize models of sustainability to maintain readiness.
June 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28518027/measles-cases-during-ebola-outbreak-west-africa-2013-2106
#8
Francesca Colavita, Mirella Biava, Concetta Castilletti, Serena Quartu, Francesco Vairo, Claudia Caglioti, Chiara Agrati, Eleonora Lalle, Licia Bordi, Simone Lanini, Michela Delli Guanti, Rossella Miccio, Giuseppe Ippolito, Maria R Capobianchi, Antonino Di Caro
The recent Ebola outbreak in West Africa caused breakdowns in public health systems, which might have caused outbreaks of vaccine-preventable diseases. We tested 80 patients admitted to an Ebola treatment center in Freetown, Sierra Leone, for measles. These patients were negative for Ebola virus. Measles virus IgM was detected in 13 (16%) of the patients.
June 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28518019/ebola-virus-imported-from-guinea-to-senegal-2014
#9
Daye Ka, Gamou Fall, Viviane Cissé Diallo, Ousmane Faye, Louise Deguenonvo Fortes, Oumar Faye, Elhadji Ibrahim Bah, Kadia Mbaye Diallo, Fanny Balique, Cheikh Tidiane Ndour, Moussa Seydi, Amadou Alpha Sall
In March 2014, the World Health Organization declared an outbreak of Ebola virus disease in Guinea. In August 2014, a case caused by virus imported from Guinea occurred in Senegal, most likely resulting from nonsecure funerals and travel. Preparedness and surveillance in Senegal probably prevented secondary cases.
June 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28516833/animal-models-of-ebolavirus-infection
#10
Marisa C St Claire, Dan R Ragland, Laura Bollinger, Peter B Jahrling
Ebola virus is a highly pathogenic member of the family Filoviridae that causes a severe hemorrhagic disease in humansand NHP. The 2013-2016 West African outbreak has increased interest in the development and refinement of animal models of Ebola virus disease. These models are used to test countermeasures and vaccines, gain scientific insights into the mechanisms of disease progression and transmission, and study key correlates of immunology. Ebola virus is classified as a BSL4 pathogen and Category A agent, for which the United States government requires preparedness in case of bioterrorism...
May 17, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28510604/ebola-exposure-illness-experience-and-ebola-antibody-prevalence-in-international-responders-to-the-west-african-ebola-epidemic-2014-2016-a-cross-sectional-study
#11
Catherine F Houlihan, Catherine R McGowan, Steve Dicks, Marc Baguelin, David A J Moore, David Mabey, Chrissy H Roberts, Alex Kumar, Dhan Samuel, Richard Tedder, Judith R Glynn
BACKGROUND: Healthcare and other front-line workers are at particular risk of infection with Ebola virus (EBOV). Despite the large-scale deployment of international responders, few cases of Ebola virus disease have been diagnosed in this group. Since asymptomatic or pauci-symptomatic infection has been described, it is plausible that infections have occurred in healthcare workers but have escaped being diagnosed. We aimed to assess the prevalence of asymptomatic or pauci-symptomatic infection, and of exposure events, among returned responders to the West African Ebola epidemic 2014-2016...
May 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28506274/contextual-and-psychosocial-factors-predicting-ebola-prevention-behaviours-using-the-ranas-approach-to-behaviour-change-in-guinea-bissau
#12
Anna E Gamma, Jurgita Slekiene, Gregor von Medeazza, Fredrik Asplund, Placido Cardoso, Hans-Joachim Mosler
BACKGROUND: The outbreak of the Ebola virus disease (EVD) in West Africa in December 2013 was the largest Ebola outbreak in history. This study aimed to measure the underlying contextual and psychosocial factors of intentions to perform Ebola prevention behaviours (not touching people who might be suffering from Ebola, reporting suspected cases to the National Ebola Hotline, NEH) in Guinea-Bissau. Geographical location, cross-border market activities, poor water, sanitation and hygiene (WASH) conditions, and burial practices in some communities pose a serious risk in terms of potential EVD outbreak and seriously hamper its prevention in Guinea-Bissau...
May 15, 2017: BMC Public Health
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
#13
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/28505171/rapid-deployment-of-a-mobile-biosafety-level-3-laboratory-in-sierra-leone-during-the-2014-ebola-virus-epidemic
#14
Yi Zhang, Yan Gong, Chengyu Wang, Wensen Liu, Zhongyi Wang, Zhiping Xia, Zhaoyang Bu, Huijun Lu, Yang Sun, Xiaoguang Zhang, Yuxi Cao, Fan Yang, Haoxiang Su, Yi Hu, Yongqiang Deng, Bo Zhou, Zongzheng Zhao, Yingying Fu, David Kargbo, Foday Dafae, Brima Kargbo, Alex Kanu, Linna Liu, Jun Qian, Zhendong Guo
BACKGROUND: Ebola virus emerged in West Africa in December 2013. The high population mobility and poor public health infrastructure in this region led to the development of the largest Ebola virus disease (EVD) outbreak to date. METHODOLOGY/PRINCIPAL FINDINGS: On September 26, 2014, China dispatched a Mobile Biosafety Level-3 Laboratory (MBSL-3 Lab) and a well-trained diagnostic team to Sierra Leone to assist in EVD diagnosis using quantitative real-time PCR, which allowed the diagnosis of suspected EVD cases in less than 4 hours from the time of sample receiving...
May 15, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28501359/the-ebola-epidemic-in-liberia-and-managing-the-dead-a-future-role-for-humanitarian-forensic-action
#15
Stephen Cordner, Heinrich Bouwer, Morris Tidball-Binz
With some of their economies, communities and health systems weakened by decades of war and poor governance, it was no accident that an epidemic of Ebola virus disease broke out in west Africa. Being spread in part by contact with body fluids of those who had died from the disease, funerary rites and the way dead bodies were managed were important modes of transmission. The Liberian Red Cross, supported by the International Federation of Red Cross and Red Crescent Societies and the International Committee of the Red Cross, undertook the challenging task of managing the dead bodies in Monrovia during the epidemic...
April 25, 2017: Forensic Science International
https://www.readbyqxmd.com/read/28498995/features-of-ebola-virus-disease-at-the-late-outbreak-stage-in-sierra-leone-clinical-virological-immunological-and-evolutionary-analyses
#16
Tao Jiang, Jia-Fu Jiang, Yong-Qiang Deng, Bao-Gui Jiang, Hang Fan, Jian-Feng Han, Yi Hu, Dao-Min Zhuang, David Kargbo, Xiao-Ping An, Zhi-Qiang Mi, Guang-Yu Zhao, Wen-Wen Xin, Ya-Fang Tan, Jun He, Rong-Bao Gao, Hong Wang, Cao Chen, Feng Wang, Chun-Xiao Li, Jian-Jun Zhao, Yu-Jun Cui, Zhu-Chun Bei, Ke Zhang, Xue-Yi Shang, Wen-Hui Zhang, Guang-Qian Pei, Yun-Fei Wang, Wei Wang, Peng Shu, Wen-Li Liu, Shi Cheng, Shun-Ya Zhu, Alex Kanu, Brima Kargbo, Bo Gao, Yi-Gang Tong, Tong-Yu Fang, Wu-Chun Cao
We performed Ebola virus disease diagnosis and viral load estimation for Ebola cases in Sierra Leone during the late stage of the 2014-2015 outbreak (January-March 2015) and analyzed antibody and cytokine levels and the viral genome sequences. Ebola virus disease was confirmed in 86 of 1001 (9.7%) patients, with an overall case fatality rate of 46.8%. Fatal cases exhibited significantly higher levels of viral loads, cytokines, and chemokines at late stages of infection versus early stage compared with survivors...
April 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28493945/ebola-virus-rna-detection-on-fomites-in-close-proximity-to-confirmed-ebola-patients-n-zerekore-guinea-2015
#17
Romain Palich, Leonid M Irenge, Eric Barte de Sainte Fare, Augustin Augier, Denis Malvy, Jean-Luc Gala
OBJECTIVE: Health care workers (HCWs) in contact with patients with Ebola virus disease (EVD) are exposed to a risk of viral contamination. Fomites contaminated with the patient's blood or body fluids represents this risk. Our study aims to detect Ebola virus (EBOV) RNA within the high- and low-risk areas of an Ebola treatment unit (ETU) located in inland Guinea during the 2014-2015 West African Ebola epidemics. For samples from patients' immediate vicinity, we aim to seek an association between viral RNA detectability and level of plasma viral load of patients (intermediate to high, or very high)...
2017: PloS One
https://www.readbyqxmd.com/read/28490747/structural-basis-for-importin-%C3%AE-binding-of-the-human-immunodeficiency-virus-tat
#18
K M Smith, Z Himiari, S Tsimbalyuk, J K Forwood
HIV-1 has caused 35 million deaths globally, and approximately the same number is currently living with HIV-1. The trans-activator of transcription (Tat) protein of HIV-1 plays an important regulatory function in the virus life cycle, responsible for regulating the reverse transcription of the viral genome RNA. Tat is found in the nucleus of infected cells, but can also invade uninfected neighbouring cells. Regions within Tat responsible for these cellular localisations are overlapping and include a nuclear localisation signal (NLS) spanning (48)GRKKRR, and a cell penetrating peptide (CPP) signal spanning (48)GRKKRRQRRRAPQN...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28490593/evolution-and-antiviral-specificity-of-interferon-induced-mx-proteins-of-bats-against-ebola-influenza-and-other-rna-viruses
#19
Jonas Fuchs, Martin Hölzer, Mirjam Schilling, Corinna Patzina, Andreas Schoen, Thomas Hoenen, Gert Zimmer, Manja Marz, Friedemann Weber, Marcel A Müller, Georg Kochs
Bats serve as a reservoir for various, often zoonotic viruses, including significant human pathogens such as Ebola- and influenza viruses. However, for unknown reasons, viral infections rarely cause clinical symptoms in bats. A tight control of viral replication by the host innate immune defense might contribute to this phenomenon. Transcriptomic studies revealed the presence of the interferon-induced antiviral myxovirus resistance (Mx) proteins in bats, but detailed functional aspects have not been assessed...
May 10, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28482272/screening-of-commercial-cyclic-peptide-conjugated-to-hiv-1-tat-peptide-as-inhibitor-of-n-terminal-heptad-repeat-glycoprotein-2-ectodomain-ebola-virus-through-in-silico-analysis
#20
Usman Sumo Friend Tambunan, Ahmad Husein Alkaff, Mochammad Arfin Fardiansyah Nasution, Arli Aditya Parikesit, Djati Kerami
Ebola Hemorrhagic Fever (EHF) is a disease caused by viruses from genus Ebolavirus. Zaire ebolavirus (EBOV) is the deadliest species which has 76% case fatality rate. Up until now, there is no U.S. Food and Drug Administration (FDA) approved drugs to treat EHF. Antiviral drug based on EBOV N-terminal heptad repeat glycoprotein-2 (NHR GP2) Ectodomain inhibitor is one kind of treatment that has not well developed. NHR GP2 Ectodomain has an important role in the process of EBOV entry into the cell through endocytosis mechanism...
April 21, 2017: Journal of Molecular Graphics & Modelling
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