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https://www.readbyqxmd.com/read/27930961/novel-activities-by-ebolavirus-and-marburgvirus-interferon-antagonists-revealed-using-a-standardized-in-vitro-reporter-system
#1
Jonathan C Guito, César G Albariño, Ayan K Chakrabarti, Jonathan S Towner
Filoviruses are highly lethal in humans and nonhuman primates, likely due to potent antagonism of host interferon (IFN) responses early in infection. Filoviral protein VP35 is implicated as the major IFN induction antagonist, while Ebola virus (EBOV) VP24 or Marburg virus (MARV) VP40 are known to block downstream IFN signaling. Despite progress elucidating EBOV and MARV antagonist function, those for most other filoviruses, including Reston (RESTV), Sudan (SUDV), Taï Forest (TAFV), Bundibugyo (BDBV) and Ravn (RAVV) viruses, remain largely neglected...
December 5, 2016: Virology
https://www.readbyqxmd.com/read/27918527/induction-and-suppression-of-antiviral-rna-interference-by-influenza-a-virus-in-mammalian-cells
#2
Yang Li, Megha Basavappa, Jinfeng Lu, Shuwei Dong, D Alexander Cronkite, John T Prior, Hans-Christian Reinecker, Paul Hertzog, Yanhong Han, Wan-Xiang Li, Sihem Cheloufi, Fedor V Karginov, Shou-Wei Ding, Kate L Jeffrey
Influenza A virus (IAV) causes annual epidemics and occasional pandemics, and is one of the best-characterized human RNA viral pathogens(1). However, a physiologically relevant role for the RNA interference (RNAi) suppressor activity of the IAV non-structural protein 1 (NS1), reported over a decade ago(2), remains unknown(3). Plant and insect viruses have evolved diverse virulence proteins to suppress RNAi as their hosts produce virus-derived small interfering RNAs (siRNAs) that direct specific antiviral defence(4-7) by an RNAi mechanism dependent on the slicing activity of Argonaute proteins (AGOs)(8,9)...
December 5, 2016: Nature Microbiology
https://www.readbyqxmd.com/read/27909582/ebola-research-funding-a-systematic-analysis-1997-2015
#3
Joseph Ra Fitchett, Amos Lichtman, Damilola T Soyode, Ariel Low, Jimena Villar de Onis, Michael G Head, Rifat Atun
BACKGROUND: The latest outbreak of Ebola in West Africa overwhelmed the affected countries, with the impact on health extending far beyond Ebola-related deaths that have exceeded 11 000. The need to promptly mobilise resources to control emerging infections is widely recognized. Yet, data on research funding for emerging infections remains inadequately documented. METHODS: We defined research investment as all funding flows for Ebola and/or Marburg virus from 1997 to April 2015 whose primary purpose was to advance knowledge and new technologies to prevent or cure disease...
December 2016: Journal of Global Health
https://www.readbyqxmd.com/read/27908828/assessment-of-the-potential-for-host-targeted-iminosugars-uv-4-and-uv-5-activity-against-filovirus-infections-in-vitro-and-in-vivo
#4
Kelly L Warfield, Travis K Warren, Xiangguo Qiu, Jay Wells, Chad E Mire, Joan B Geisbert, Kelly S Stuthman, Nicole L Garza, Sean A Van Tongeren, Amy C Shurtleff, Krystle N Agans, Gary Wong, Michael V Callahan, Thomas W Geisbert, Brennan Klose, Urban Ramstedt, Anthony M Treston
Iminosugars are host-directed antivirals with broad-spectrum activity. The iminosugar, N-butyl-deoxynojirimycin (NB-DNJ or Miglustat(®)), is used in humans for treatment of Gaucher's disease and has mild antiviral properties. More potent analogs of NB-DNJ have been generated and have demonstrated activity against a variety of viruses including flaviviruses, influenza, herpesviruses and filoviruses. In the current study, a panel of analogs based on NB-DNJ was analyzed for activity against Ebola (EBOV) and Marburg viruses (MARV)...
November 28, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27887599/how-severe-and-prevalent-are-ebola-and-marburg-viruses-a-systematic-review-and-meta-analysis-of-the-case-fatality-rates-and-seroprevalence
#5
Luke Nyakarahuka, Clovice Kankya, Randi Krontveit, Benjamin Mayer, Frank N Mwiine, Julius Lutwama, Eystein Skjerve
BACKGROUND: Ebola and Marburg virus diseases are said to occur at a low prevalence, but are very severe diseases with high lethalities. The fatality rates reported in different outbreaks ranged from 24-100%. In addition, sero-surveys conducted have shown different seropositivity for both Ebola and Marburg viruses. We aimed to use a meta-analysis approach to estimate the case fatality and seroprevalence rates of these filoviruses, providing vital information for epidemic response and preparedness in countries affected by these diseases...
November 25, 2016: BMC Infectious Diseases
https://www.readbyqxmd.com/read/27847355/crystal-structure-of-the-marburg-virus-vp35-oligomerization-domain
#6
Jessica F Bruhn, Robert N Kirchdoerfer, Sarah M Urata, Sheng Li, Ian J Tickle, Gérard Bricogne, Erica Ollmann Saphire
: Marburg virus (MARV) is a highly pathogenic filovirus that is classified in a distinct genus from Ebola virus (EBOV) (genera Marburgvirus and Ebolavirus). Both viruses produce a multifunctional protein termed VP35, which acts as a polymerase co-factor, a viral protein chaperone and an antagonist of the innate immune response. VP35 contains a central oligomerization domain with a predicted coiled-coil motif. This domain has been shown to be essential for RNA polymerase function. Here we present crystal structures of the MARV VP35 oligomerization domain...
November 9, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27811840/notes-from-the-field-rift-valley-fever-response-kabale-district-uganda-march-2016
#7
Annabelle de St Maurice, Luke Nyakarahuka, Lawrence Purpura, Elizabeth Ervin, Alex Tumusiime, Stephen Balinandi, Jackson Kayondo, Sophia Mulei, Anne Marion Namutebi, Patrick Tusiime, Steven Wiersma, Stuart Nichol, Pierre Rollin, John Klena, Barbara Knust, Trevor Shoemaker
On March 9, 2016, a male butcher from Kabale District, Uganda, aged 45 years, reported to the Kabale Regional Referral Hospital with fever, fatigue, and headache associated with black tarry stools and bleeding from the nose. One day later, a student aged 16 years from a different sub-county in Kabale District developed similar symptoms and was admitted to the same hospital. The student also had a history of contact with livestock. Blood specimens collected from both patients were sent for testing for Marburg virus disease, Ebola virus disease, Rift Valley fever (RVF), and Crimean Congo Hemorrhagic fever at the Uganda Virus Research Institute, as part of the viral hemorrhagic fevers surveillance program...
November 4, 2016: MMWR. Morbidity and Mortality Weekly Report
https://www.readbyqxmd.com/read/27807228/tim-1-promotes-hepatitis-c-virus-cell-attachment-and-infection
#8
Jing Wang, Luhua Qiao, Zhouhua Hou, Guangxiang Luo
: Human TIM and TAM family proteins were recently found to serve as phosphatidylserine receptors which promote infection of many different viruses including dengue virus, West Nile virus, Ebola virus, Marburg virus, and Zika virus. In the present study, we provide substantial evidence demonstrating that TIM-1 is important for efficient infection of hepatitis C virus (HCV). The knockdown of TIM-1 expression significantly reduced HCV infection but not HCV RNA replication. Likewise, TIM-1 knockout in Huh-7...
November 2, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27755595/the-ebola-virus-vp30-np-interaction-is-a-regulator-of-viral-rna-synthesis
#9
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
https://www.readbyqxmd.com/read/27753082/costs-and-cost-driving-factors-for-acute-treatment-of-adults-with-status-epilepticus-a-multicenter-cohort-study-from-germany
#10
Lena-Marie Kortland, Anne Alfter, Oliver Bähr, Barbara Carl, Richard Dodel, Thomas M Freiman, Kristina Hubert, Kolja Jahnke, Susanne Knake, Felix von Podewils, Jens-Peter Reese, Uwe Runge, Christian Senft, Helmuth Steinmetz, Felix Rosenow, Adam Strzelczyk
OBJECTIVE: To provide first data on inpatient costs and cost-driving factors due to nonrefractory status epilepticus (NSE), refractory status epilepticus (RSE), and super-refractory status epilepticus (SRSE). METHODS: In 2013 and 2014, all adult patients treated due to status epilepticus (SE) at the university hospitals in Frankfurt, Greifswald, and Marburg were analyzed for healthcare utilization. RESULTS: We evaluated 341 admissions in 316 patients (65...
October 18, 2016: Epilepsia
https://www.readbyqxmd.com/read/27746781/comparative-analysis-of-clinical-scale-ifn-%C3%AE-positive-t-cell-enrichment-using-partially-and-fully-integrated-platforms
#11
Christoph Priesner, Ruth Esser, Sabine Tischer, Michael Marburger, Krasimira Aleksandrova, Britta Maecker-Kolhoff, Hans-Gert Heuft, Lilia Goudeva, Rainer Blasczyk, Lubomir Arseniev, Ulrike Köhl, Britta Eiz-Vesper, Stephan Klöß
BACKGROUND AND AIMS: The infusion of enriched CMV-specific donor T-cells appears to be a suitable alternative for the treatment of drug-resistant CMV reactivation or de novo infection after both solid organ and hematopoietic stem cell transplantation. Antiviral lymphocytes can be selected from apheresis products using the CliniMACS Cytokine-Capture-System(®) either with the well-established CliniMACS(®) Plus (Plus) device or with its more versatile successor CliniMACS Prodigy(®) (Prodigy)...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27736754/favipiravir-pharmacokinetics-in-non-human-primates-insights-for-future-efficacy-studies-of-haemorrhagic-fever-viruses
#12
Vincent Madelain, Jérémie Guedj, France Mentré, Thi Huyen Tram Nguyen, Frédéric Jacquot, Lisa Oestereich, Takumi Kadota, Koichi Yamada, Anne-Marie Taburet, Xavier de Lamballerie, Hervé Raoul
Favipiravir is a RNA polymerase inhibitor that showed a strong antiviral efficacy in vitro and in small animal models of several viruses responsible for hemorrhagic fever (HF) including Ebola virus. The aim of this work was to characterize the complex pharmacokinetics of favipiravir in non-human primates (NHP) in order to guide future efficacy studies of favipiravir in large animal models.Four different studies were conducted in 30 uninfected cynomolgus macaques of Chinese (n=17) or Mauritian (n=13) origin treated with intravenous favipiravir for 7 to 14 days with maintenance doses of 60 to 180 mg/kg BID...
October 10, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27723926/-obstacles-and-opportunities-for-the-psychotherapeutic-treatment-of-asylum-seekers
#13
Ricarda Mewes, Lea Kowarsch, Hanna Reinacher, Urs M Nater
Introduction: The number of refugees and asylum seekers in Germany is high. Presumably, the need for psychotherapeutic care is high in this group. However, this need stands in contrast to a lack of a specialized and widespread provision of such care. Registered psychotherapists could help to partially reduce this gap. The present study aimed at learning more about the expected or experienced obstacles and opportunities of registered psychotherapists in regard to the psychotherapeutic treatment of asylum seekers in Germany...
September 2016: Psychotherapie, Psychosomatik, Medizinische Psychologie
https://www.readbyqxmd.com/read/27716429/serosurveillance-of-viral-pathogens-circulating-in-west-africa
#14
Aileen E O'Hearn, Matthew A Voorhees, David P Fetterer, Nadia Wauquier, Moinya R Coomber, James Bangura, Joseph N Fair, Jean-Paul Gonzalez, Randal J Schoepp
BACKGROUND: Sub-Saharan Africa is home to a variety of pathogens, but disease surveillance and the healthcare infrastructure necessary for proper management and control are severely limited. Lassa virus, the cause of Lassa fever, a severe hemorrhagic fever in humans is endemic in West Africa. In Sierra Leone at the Kenema Government Hospital Lassa Diagnostic Laboratory, up to 70 % of acute patient samples suspected of Lassa fever test negative for Lassa virus infection. This large amount of acute undiagnosed febrile illness can be attributed in part to an array of hemorrhagic fever and arthropod-borne viruses causing disease that goes undetected and untreated...
October 3, 2016: Virology Journal
https://www.readbyqxmd.com/read/27713552/differential-transcriptional-responses-to-ebola-and-marburg-virus-infection-in-bat-and-human-cells
#15
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
https://www.readbyqxmd.com/read/27712998/inhibitors-of-retrograde-trafficking-active-against-ricin-and-shiga-toxins-also-protect-cells-from-several-viruses-leishmania-and-chlamydiales
#16
Neetu Gupta, Romain Noël, Amélie Goudet, Karen Hinsinger, Aurélien Michau, Valérie Pons, Hajer Abdelkafi, Thomas Secher, Ayaka Shima, Olena Shtanko, Yasuteru Sakurai, Sandrine Cojean, Sébastien Pomel, Vanessa Liévin-Le Moal, Véronique Leignel, Jo-Ana Herweg, Annette Fischer, Ludger Johannes, Kate Harrison, Philippa M Beard, Pascal Clayette, Roger Le Grand, Jonathan O Rayner, Thomas Rudel, Joël Vacus, Philippe M Loiseau, Robert A Davey, Eric Oswald, Jean-Christophe Cintrat, Julien Barbier, Daniel Gillet
Medical countermeasures to treat biothreat agent infections require broad-spectrum therapeutics that do not induce agent resistance. A cell-based high-throughput screen (HTS) against ricin toxin combined with hit optimization allowed selection of a family of compounds that meet these requirements. The hit compound Retro-2 and its derivatives have been demonstrated to be safe in vivo in mice even at high doses. Moreover, Retro-2 is an inhibitor of retrograde transport that affects syntaxin-5-dependent toxins and pathogens...
October 3, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27640102/filovirus-proteins-for-antiviral-drug-discovery-a-structure-function-analysis-of-surface-glycoproteins-and-virus-entry
#17
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
https://www.readbyqxmd.com/read/27636904/activated-protein-c-resistance-in-patients-following-venous-thromboembolism-receiving-rivaroxaban-versus-vitamin-k-antagonists-assessment-using-russell-viper-venom-time-based-assay
#18
Tadeusz Goralczyk, Katarzyna B Wojtowicz, Anetta Undas
Activated protein C resistance (APC-R) is assessed as part of thrombophilia screening, preferably in patients not taking oral anticoagulants. Rivaroxaban is known to alter some APC-R assays. To our knowledge, there have been no reports on the effect of rivaroxaban on the Russell viper venom time (RVVT)-based APC-R assay in real-life patients. In 168 consecutive outpatients suspected of having venous thromboembolism because of thrombophilia, APC-R was determined using the RVVT-based ProC Ac R assay (Siemens, Marburg, Germany)...
September 15, 2016: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/27619056/isolation-of-tioman-virus-from-pteropus-giganteus-bat-in-north-east-region-of-india
#19
Pragya Yadav, Prasad Sarkale, Deepak Patil, Anita Shete, Prasad Kokate, Vimal Kumar, Rajlaxmi Jain, Santosh Jadhav, Atanu Basu, Shailesh Pawar, Anakkathil Sudeep, Mangesh Gokhale, Rajen Lakra, Devendra Mourya
Bat-borne viral diseases are a major public health concern among newly emerging infectious diseases which includes severe acute respiratory syndrome, Nipah, Marburg and Ebola virus disease. During the survey for Nipah virus among bats at North-East region of India; Tioman virus (TioV), a new member of the Paramyxoviridae family was isolated from tissues of Pteropus giganteus bats for the first time in India. This isolate was identified and confirmed by RT-PCR, sequence analysis and electron microscopy. A range of vertebrate cell lines were shown to be susceptible to Tioman virus...
September 9, 2016: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/27618323/white-matter-diseases-with-radiologic-pathologic-correlation
#20
Nicolae Sarbu, Robert Y Shih, Robert V Jones, Iren Horkayne-Szakaly, Laura Oleaga, James G Smirniotopoulos
White matter diseases include a wide spectrum of disorders that have in common impairment of normal myelination, either by secondary destruction of previously myelinated structures (demyelinating processes) or by primary abnormalities of myelin formation (dysmyelinating processes). The pathogenesis of many white matter diseases remains poorly understood. Demyelinating disorders are the object of this review and will be further divided into autoimmune, infectious, vascular, and toxic-metabolic processes. Autoimmune processes include multiple sclerosis and related diseases: tumefactive demyelinating lesions, Balo concentric sclerosis, Marburg and Schilder variants, neuromyelitis optica (Devic disease), acute disseminated encephalomyelitis, and acute hemorrhagic leukoencephalopathy (Hurst disease)...
September 2016: Radiographics: a Review Publication of the Radiological Society of North America, Inc
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