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Julia Nehls, Ramona Businger, Markus Hoffmann, Constantin Brinkmann, Birgit Fehrenbacher, Martin Schaller, Brigitte Maurer, Caroline Schönfeld, Daniela Kramer, Stephan Hailfinger, Stefan Pöhlmann, Michael Schindler
The Ebola virus glycoprotein (EBOV-GP) forms GP-containing microvesicles, so-called virosomes, which are secreted from GP-expressing cells. However, determinants of GP-virosome release and their functionality are poorly understood. We characterized GP-mediated virosome formation and delineated the role of the antiviral factor tetherin (BST2, CD317) in this process. Residues in the EBOV-GP receptor-binding domain (RBD) promote GP-virosome secretion, while tetherin suppresses GP-virosomes by interactions involving the GP-transmembrane domain...
February 12, 2019: Cell Reports
Shao-Li Hong, Meng-Qi Xiang, Man Tang, Dai-Wen Pang, Zhi-Ling Zhang
Aptamers of Ebola virus (EBOV) offer a powerful means for the prevention and diagnostics. Unfortunately, few of aptamers for EBOV are discovered yet. Herein, assisted by magnetism-controlled selection chip to strictly manipulate selection conditions, a highly efficient aptamer selection platform for EBOV is proposed. With the high-stringency selection conditions of rigorous washing, minuscule amount of magnetic beads manipulating and real-time evaluation of the selection effectiveness, the selection performance of platform was improved significantly...
February 11, 2019: Analytical Chemistry
Carly Fleagle Chisholm, Taek Jin Kang, Miao Dong, Kasey Lewis, Madhuri Namekar, Axel T Lehrer, Theodore W Randolph
No United States Food and Drug Administration-licensed vaccines protective against Ebola virus (EBOV) infections are currently available. EBOV vaccine candidates currently in development, as well as most currently licensed vaccines in general, require transport and storage under a continuous cold chain in order to prevent potential decreases in product efficacy. Cold chain requirements are particularly difficult to maintain in developing countries. To improve thermostability and reduce costly cold chain requirements, a subunit protein vaccine against EBOV was formulated as a glassy solid using lyophilization...
January 28, 2019: European Journal of Pharmaceutics and Biopharmaceutics
C E Hulseberg, L Fénéant, K M Szymańska-de Wijs, N P Kessler, E A Nelson, C J Shoemaker, C S Schmaljohn, S J Polyak, J M White
Antiviral therapies that impede virus entry are attractive because they act on the first phase of the infectious cycle. Drugs that target pathways common to multiple viruses are particularly desirable when laboratory-based viral identification may be challenging, e.g. in an outbreak setting. We are interested in identifying drugs that block both Ebola virus (EBOV) and Lassa virus (LASV), two unrelated but highly pathogenic hemorrhagic fever viruses that have caused outbreaks in similar regions in Africa and share features of virus entry: use of cell surface attachment factors, macropinocytosis, endosomal receptors and low pH to trigger fusion in late endosomes...
January 30, 2019: Journal of Virology
Matthew A Dragovich, Nicole Fortoul, Anand Jagota, Wei Zhang, Krista Schutt, Yan Xu, Michelle Sanabria, Dennis M Moyer, Sven Moller-Tank, Wendy Maury, X Frank Zhang
Since the most recent outbreak, the Ebola virus (EBOV) epidemic remains one of the world's public health and safety concerns. EBOV is a negative-sense RNA virus that can infect humans and non-human primates, and causes hemorrhagic fever. It has been proposed that the T-cell immunoglobulin and mucin domain (TIM) family proteins act as cell surface receptors for EBOV, and that the interaction between TIM and phosphatidylserine (PS) on the surface of EBOV mediates the EBOV-host cell attachment. Despite these initial findings, the biophysical properties of the TIM-EBOV interaction, such as the mechanical strength of the TIM-PS bond that allows the virus-cell interaction to resist external mechanical perturbations, have not yet been characterized...
January 22, 2019: Scientific Reports
Mike Flint, Payel Chatterjee, David L Lin, Laura K McMullan, Punya Shrivastava-Ranjan, Éric Bergeron, Michael K Lo, Stephen R Welch, Stuart T Nichol, Andrew W Tai, Christina F Spiropoulou
There are no approved therapies for Ebola virus infection. Here, to find potential therapeutic targets, we perform a screen for genes essential for Ebola virus (EBOV) infection. We identify GNPTAB, which encodes the α and β subunits of N-acetylglucosamine-1-phosphate transferase. We show that EBOV infection of a GNPTAB knockout cell line is impaired, and that this is reversed by reconstituting GNPTAB expression. Fibroblasts from patients with mucolipidosis II, a disorder associated with mutations in GNPTAB, are refractory to EBOV, whereas cells from their healthy parents support infection...
January 17, 2019: Nature Communications
Petrus Jansen van Vuren, Jason T Ladner, Antoinette A Grobbelaar, Michael R Wiley, Sean Lovett, Mushal Allam, Arshad Ismail, Chantel le Roux, Jacqueline Weyer, Naazneen Moolla, Nadia Storm, Joe Kgaladi, Mariano Sanchez-Lockhart, Ousman Conteh, Gustavo Palacios, Janusz T Paweska
We generated genome sequences from 218 cases of Ebola virus disease (EVD) in Sierra Leone (SLE) during 2014⁻2015 to complement available datasets, particularly by including cases from a period of low sequence coverage during peak transmission of Ebola virus (EBOV) in the highly-affected Western Area division of SLE. The combined dataset was utilized to produce phylogenetic and phylodynamic inferences, to study sink⁻source dynamics and virus dispersal from highly-populated transmission hotspots. We identified four districts in SLE where EBOV was introduced and transmission occurred without onward exportation to other districts...
January 16, 2019: Viruses
Jennifer M Brannan, Shihua He, Katie A Howell, Laura I Prugar, Wenjun Zhu, Hong Vu, Sergey Shulenin, Shweta Kailasan, Henna Raina, Gary Wong, Md Niaz Rahim, Logan Banadyga, Kevin Tierney, Xuelian Zhao, Yuxing Li, Frederick W Holtsberg, John M Dye, Xiangguo Qiu, M Javad Aman
The 2013-2016 Ebola virus (EBOV) disease epidemic demonstrated the grave consequences of filovirus epidemics in the absence of effective therapeutics. Besides EBOV, two additional ebolaviruses, Sudan (SUDV) and Bundibugyo (BDBV) viruses, as well as multiple variants of Marburg virus (MARV), have also caused high fatality epidemics. Current experimental EBOV monoclonal antibodies (mAbs) are ineffective against SUDV, BDBV, or MARV. Here, we report that a cocktail of two broadly neutralizing ebolavirus mAbs, FVM04 and CA45, protects nonhuman primates (NHPs) against EBOV and SUDV infection when delivered four days post infection...
January 10, 2019: Nature Communications
Zachary A Bornholdt, Andrew S Herbert, Chad E Mire, Shihua He, Robert W Cross, Anna Z Wec, Dafna M Abelson, Joan B Geisbert, Rebekah M James, Md Niaz Rahim, Wenjun Zhu, Viktoriya Borisevich, Logan Banadyga, Bronwyn M Gunn, Krystle N Agans, Ariel S Wirchnianski, Eileen Goodwin, Kevin Tierney, William S Shestowsky, Ognian Bohorov, Natasha Bohorova, Jesus Velasco, Eric Ailor, Do Kim, Michael H Pauly, Kevin J Whaley, Galit Alter, Laura M Walker, Kartik Chandran, Larry Zeitlin, Xiangguo Qiu, Thomas W Geisbert, John M Dye
Recent and ongoing outbreaks of Ebola virus disease (EVD) underscore the unpredictable nature of ebolavirus reemergence and the urgent need for antiviral treatments. Unfortunately, available experimental vaccines and immunotherapeutics are specific for a single member of the Ebolavirus genus, Ebola virus (EBOV), and ineffective against other ebolaviruses associated with EVD, including Sudan virus (SUDV) and Bundibugyo virus (BDBV). Here we show that MBP134AF , a pan-ebolavirus therapeutic comprising two broadly neutralizing human antibodies (bNAbs), affords unprecedented effectiveness and potency as a therapeutic countermeasure to antigenically diverse ebolaviruses...
January 9, 2019: Cell Host & Microbe
Anna Z Wec, Zachary A Bornholdt, Shihua He, Andrew S Herbert, Eileen Goodwin, Ariel S Wirchnianski, Bronwyn M Gunn, Zirui Zhang, Wenjun Zhu, Guodong Liu, Dafna M Abelson, Crystal L Moyer, Rohit K Jangra, Rebekah M James, Russell R Bakken, Natasha Bohorova, Ognian Bohorov, Do H Kim, Michael H Pauly, Jesus Velasco, Robert H Bortz, Kevin J Whaley, Tracey Goldstein, Simon J Anthony, Galit Alter, Laura M Walker, John M Dye, Larry Zeitlin, Xiangguo Qiu, Kartik Chandran
Passive administration of monoclonal antibodies (mAbs) is a promising therapeutic approach for Ebola virus disease (EVD). However, all mAbs and mAb cocktails that have entered clinical development are specific for a single member of the Ebolavirus genus, Ebola virus (EBOV), and ineffective against outbreak-causing Bundibugyo virus (BDBV) and Sudan virus (SUDV). Here, we advance MBP134, a cocktail of two broadly neutralizing human mAbs, ADI-15878 from an EVD survivor and ADI-23774 from the same survivor but specificity-matured for SUDV GP binding affinity, as a candidate pan-ebolavirus therapeutic...
January 9, 2019: Cell Host & Microbe
Ami Patel, David B Weiner
Pan-Ebolavirus immunotherapy would provide a rapid-response treatment during Ebola virus outbreaks. In this issue of Cell Host & Microbe, Wec et al. (2019) and Bornholdt et al. (2019) optimize the MBP134 mAb cocktail through antibody affinity maturation, improving its protective efficacy against three Ebolaviruses: EBOV, SUDV, and BDBV.
January 9, 2019: Cell Host & Microbe
Xing-Lou Yang, Chee Wah Tan, Danielle E Anderson, Ren-Di Jiang, Bei Li, Wei Zhang, Yan Zhu, Xiao Fang Lim, Peng Zhou, Xiang-Ling Liu, Wuxiang Guan, Libiao Zhang, Shi-Yue Li, Yun-Zhi Zhang, Lin-Fa Wang, Zheng-Li Shi
Filoviruses, especially Ebola virus (EBOV) and Marburg virus (MARV), are notoriously pathogenic and capable of causing severe haemorrhagic fever diseases in humans with high lethality1,2 . The risk of future outbreaks is exacerbated by the discovery of other bat-borne filoviruses of wide genetic diversity globally3-5 . Here we report the characterization of a phylogenetically distinct bat filovirus, named Měnglà virus (MLAV). The coding-complete genome of MLAV shares 32-54% nucleotide sequence identity with known filoviruses...
January 7, 2019: Nature Microbiology
Asuka Nanbo, Yoshihiro Kawaoka
Ebola virus (EBOV) is an enveloped filamentous virus that causes severe hemorrhagic fever in humans and nonhuman primates with up to 90% fatality. Accumulating evidence indicates that various viruses, including EBOV, exploit the host apoptotic clearance machinery to enhance their entry into host cells by externalizing phosphatidylserine (PS) in the viral envelope. PS is typically distributed in the inner layer of the plasma membrane (PM) in normal cells. Progeny EBOV virions bud from the PM of infected cells, suggesting that PS is likely flipped to the outer leaflet of the envelope of Ebola virions...
January 7, 2019: DNA and Cell Biology
Leopoldo Spadea, Nicola Iozzo
No abstract text is available yet for this article.
November 2018: Annals of Translational Medicine
Yanqiu Wei, Yongcheng Duan, Yuhai Bi, Meng Wang, Yunlong Li, Xuan Wang, Wei Li, Wenhui Fan, Jing Wang, Wenjun Liu, Limin Yang
Ebola virus (EBOV) is an extremely contagious pathogen first discovered in Africa associated with severe hemorrhagic disease in humans and nonhuman primates, which has resulted in at least 28 500 suspected cases and 11 300 confirmed deaths in 2014-2016 Ebola epidemic in West Africa. Rapid and sensitive detection of EBOV is the key to increasing the probability of survival and reducing infection rates in pandemic regions. Here, we report an ultrasensitive and instrument-free EBOV detection assay based on colloidal carbon immunochromatography...
December 25, 2018: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
Kerrie Vaughan, Xiaojun Xu, Bjoern Peters, Alessandro Sette
The global response to the most recent EBOV outbreak has led to increased generation and availability of data, which can be globally analyzed to increase our understanding of immune responses to EBOV. We analyzed the published antibody epitope data to identify regions immunogenic for humans on the main GP antigenic target and determine sequence variance/nonsynonymous mutations between historical isolates and variants from the 2013-2016 outbreak. Approximately half of the GP sequence has been reported as targeted by antibody responses...
2018: Journal of Immunology Research
Rohan Keshwara, Katie R Hagen, Tiago Abreu-Mota, Amy B Papaneri, David Liu, Christoph Wirblich, Reed F Johnson, Matthias J Schnell
Marburg virus (MARV) is a filovirus related to Ebola virus (EBOV) associated with human hemorrhagic disease. Outbreaks are sporadic and severe with a reported case mortality rate upward of 88%. There is currently no antiviral or vaccine available. Given the sporadic nature of outbreaks, vaccines provide the best approach for long-term control of MARV in endemic regions. We have developed an inactivated rabies virus-vectored MARV vaccine (FILORAB3) to protect against Marburg virus disease. Immunogenicity studies in our lab have shown that a Th1-biased seroconversion to both RABV and MARV glycoproteins is beneficial for protection in a preclinical murine model...
December 19, 2018: Journal of Virology
Christopher F Basler, Nevan J Krogan, Daisy W Leung, Gaya K Amarasinghe
Filoviruses, which include Ebola virus (EBOV) and Marburg virus, are negative-sense RNA viruses associated with sporadic outbreaks of severe viral hemorrhagic fever characterized by uncontrolled virus replication. The extreme virulence and emerging nature of these zoonotic pathogens make them a significant threat to human health. Replication of the filovirus genome and production of viral RNAs require the function of a complex of four viral proteins, the nucleoprotein (NP), viral protein 35 (VP35), viral protein 30 (VP30) and large protein (L)...
December 11, 2018: Antiviral Research
Jyoti Batra, Judd F Hultquist, Dandan Liu, Olena Shtanko, John Von Dollen, Laura Satkamp, Gwendolyn M Jang, Priya Luthra, Toni M Schwarz, Gabriel I Small, Eusondia Arnett, Manu Anantpadma, Ann Reyes, Daisy W Leung, Robyn Kaake, Paige Haas, Carson B Schmidt, Larry S Schlesinger, Douglas J LaCount, Robert A Davey, Gaya K Amarasinghe, Christopher F Basler, Nevan J Krogan
Ebola virus (EBOV) infection often results in fatal illness in humans, yet little is known about how EBOV usurps host pathways during infection. To address this, we used affinity tag-purification mass spectrometry (AP-MS) to generate an EBOV-host protein-protein interaction (PPI) map. We uncovered 194 high-confidence EBOV-human PPIs, including one between the viral transcription regulator VP30 and the host ubiquitin ligase RBBP6. Domain mapping identified a 23 amino acid region within RBBP6 that binds to VP30...
December 13, 2018: Cell
Hualei Wang, Gary Wong, Wenjun Zhu, Shihua He, Yongkun Zhao, Feihu Yan, Md Niaz Rahim, Yuhai Bi, Zirui Zhang, Keding Cheng, Hongli Jin, Zengguo Cao, Xuexing Zheng, Weiwei Gai, Jieying Bai, Weijin Chen, Yong Zou, Yuwei Gao, George F Gao, Songtao Yang, Xianzhu Xia, Xiangguo Qiu
Ebola virus (EBOV) infections result in aggressive hemorrhagic fever in humans with fatality rates reaching 90%, with no licensed, specific therapeutics to treat ill patients. Advances over the past 5 years have firmly established monoclonal antibody (mAb)-based products as the most promising therapeutics for treating EBOV infections, but production is costly, quantities are limited, and thus mAbs are not the best candidates for mass use in the case of an epidemic. To address this need, we generated EBOV-specific polyclonal immunoglobulin fragments F(ab')2 from horses hyperimmunized with an EBOV vaccine...
December 12, 2018: Journal of Virology
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