Viruses, Vol. 11, Pages 137: Filovirus Virulence in Interferon α/β and γ Double Knockout Mice, and Treatment with Favipiravir

Viruses, Vol. 11, Pages 137: Filovirus Virulence in Interferon α/β and γ Double Knockout Mice, and Treatment with Favipiravir Viruses doi: 10.3390/v11020137 Authors: Jason E. Comer Olivier Escaffre Natasha Neef Trevor Brasel Terry L. Juelich Jennifer K. Smith Jeanon Smith Birte Kalveram David D. Perez Shane Massey Lihong Zhang Alexander N. Freiberg The 2014 Ebolavirus outbreak in West Africa highlighted the need for vaccines and therapeutics to prevent and treat filovirus infections. A well-characterized small animal model that is susceptible to wild-type filoviruses would facilitate the screening of anti-filovirus agents. To that end, we characterized knockout mice lacking α/β and γ interferon receptors (IFNAGR KO) as a model for wild-type filovirus infection. Intraperitoneal challenge of IFNAGR KO mice with several known human pathogenic species from the genus Ebolavirus and Marburgvirus, except Bundibugyo ebolavirus and Taï Forest ebolavirus, caused variable mortality rate. Further characterization of the prototype Ebola virus Kikwit isolate infection in this KO mouse model showed 100% lethality down to a dilution equivalent to 1.0 × 10−1 pfu with all deaths occurring between 7 and 9 days post-challenge. Viral RNA was detectable in serum after challenge with 1.0 × 102 pfu as early as one day after infection. Changes in hematology and serum chemistry became pro...
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research

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Ebola virus is a large, negative-strand RNA virus composed of 7 genes encoding viral proteins, including a single glycoprotein (GP). The virus is responsible for causing Ebola virus disease (EVD), formerly known as Ebola hemorrhagic fever (EHF), in humans. In particular, Bundibugyo (BDBV), Zaire (EBOV), and Sudan (SUDV) species have been associated with large outbreaks of EVD in Africa and reported case fatality rates of up to 90%. Transmission of Ebola virus to humans is not yet fully understood but is likely due to incidental exposure to infected animals. EVD spreads through human-to-human transmission, with infection re...
Source: NIH OTT Licensing Opportunities - Category: Research Authors: Source Type: research
Recent occurrences of filoviruses and the arenavirus Lassa virus (LASV) in overlapping endemic areas of Africa highlight the need for a prophylactic vaccine that would confer protection against all of these viruses that cause lethal hemorrhagic fever (HF). We developed a quadrivalent formulation of VesiculoVax that contains recombinant vesicular stomatitis virus (rVSV) vectors expressing filovirus glycoproteins and that also contains a rVSV vector expressing the glycoprotein of a lineage IV strain of LASV. Cynomolgus macaques were vaccinated twice with the quadrivalent formulation, followed by challenge 28 days after the b...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
by Brien K. Haun, Varney Kamara, Abigail S. Dweh, Kianalei Garalde-Machida, Saymajunkon S. E. Forkay, Melissa Takaaze, Madhuri Namekar, Teri Ann S. Wong, Ayesha E. R. Bell-Gam Woto, Peter Humphreys, Ophelia I. Weeks, Mosoka P. Fallah, John M. Berestecky, Vivek R. Nerurkar, Axel T. Lehrer Filoviruses such as Ebola virus (EBOV) cause outbreaks of viral hemorrhagic fevers for which no FDA-approved vaccines or drugs are available. The 2014–2016 EBOV outbreak in West Africa infected approximately 30,000 people, killing more than 11,000 and affecting thousands more in areas still suff ering from the effects of civil wars....
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research
Ebola Virus Disease (EVD) is a disease caused by infection with viruses from the familyFiloviridae, genusEbolavirus. Ebola virus was first discovered in 1976 in Africa and has since caused numerous outbreaks throughout the continent including the largest outbreak in history in West Africa during 2014-2016. Previously, there were three identified Ebolavirus species which were known to cause disease in humans: Ebola virus (Zaire ebolavirus); Sudan virus (Sudan ebolavirus); and Tai Forest virus (Tai Forest ebolavirus). CDC discovered a fourth novel virus, first identified in Uganda, Bundibugyo virus (Bundibugyo ebolavirus). T...
Source: NIH OTT Licensing Opportunities - Category: Research Authors: Source Type: research
Abstract As part of the scientific community's development of medical countermeasures against Ebola virus disease, optimization of standardized assays for product evaluation is paramount. The recent outbreak heightened awareness to the scarcity of available assays and limited information on performance and reproducibility. To evaluate the immunogenicity of vaccines entering Phase I-III trials and to identify survivors, two enzyme-linked immunosorbent assays, the Filovirus Animal Non-Clinical Group assay and the Alpha Diagnostics International assay, were evaluated for detection of immunoglobulin G against Ebola vi...
Source: Journal of Virological Methods - Category: Virology Authors: Tags: J Virol Methods Source Type: research
Griffiths Ebola virus (EBOV) is a filovirus that can cause Ebola virus disease (EVD). No approved vaccines or therapies exist for filovirus infections, despite an urgent need. The development and testing of effective countermeasures against EBOV requires use of animal models and a thorough understanding of how the model aligns with EVD in humans. The majority of published studies report outcomes of parenteral exposures for emulating needle stick transmission. However, based on data from EVD outbreaks, close contact exposures to infected bodily fluid seems to be one of the primary routes of EBOV transmission. Thus, furt...
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research
Abstract 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. Rodents, suc...
Source: Comparative Medicine - Category: Zoology Authors: Tags: Comp Med Source Type: research
AbstractThe 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. There are no licensed vaccines or therapeutics available...
Source: Virus Genes - Category: Genetics & Stem Cells Source Type: research
U.S. Department of Defense, Joint Program Executive Office for Chemical and Biological Defense. 10/23/2015This resource provides information, presentation slides, and transcripts from a workshop on filovirus medical countermeasures held on October 20-23, 2015. It featured a discussion about how to bridge nonclinical data to the human data, analysis of vaccine endpoints to support establishing a correlate of protection, and information about gaining a better understanding of the difference between the in vitro and in vivo models to test therapeutics. Other topics included vaccines, the Ebola outbreak, and FANG (Filovirus An...
Source: Disaster Lit: Resource Guide for Disaster Medicine and Public Health - Category: Global & Universal Authors: Source Type: news
Introduction Ebola virus disease (EVD), previously known as Ebola hemorrhagic fever is a rare and deadly acute viral illness caused by Filoviridae family. Ebola can cause disease in both humans and nonhuman primates (monkeys, gorillas, and chimpanzees). EVD causes severe and often fatal illness in humans and has a case fatality rate of up to 90% if left untreated1,2. The first outbreak of the disease was reported in 1976, in two simultaneous outbreaks in Yambuku, Democratic Republic of Congo in a village situated near the Ebola River, from which the disease derives its name and in Nzara, Sudan2,3. The natural reservoir of ...
Source: PLOS Currents Outbreaks - Category: Epidemiology Authors: Source Type: research
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