title: Rodent-Adapted Filoviruses and the Molecular Basis of Pathogenesis.
abstract: Ebola, Marburg, and Ravn viruses, all filoviruses, are the causative agents of severe hemorrhagic fever. Much of what we understand about the pathogenesis of filovirus disease is derived from work with animal models, including nonhuman primates, which are considered the "gold standard" filovirus model since they faithfully recapitulate the clinical hallmarks of filovirus disease. However, rodent models, including the mouse, guinea pig, and hamster, also exist for Ebola, Marburg, and Ravn viruses, and although they may not reproduce all the clinical signs of filovirus disease, thanks to their relative ease of use and low cost, they are often the first choice for initial descriptions of virus pathogenesis and evaluation of antiviral prophylactics and therapeutics. Since filoviruses do not cause significant disease in adult, immunocompetent rodents, these models rely on "rodent-adapted" viruses that have been passaged several times through their host until virulence and lethality are achieved. In the process of adaptation, the viruses acquire numerous nucleotide/amino acid mutations that contribute to virulence in their rodent host. Interestingly, virus protein 24 (VP24) and nucleoprotein (NP) appear to be major virulence factors for ebolaviruses in rodents, whereas VP40 appears to be the major virulence factor for marburgviruses. By characterizing these mutations and understanding the molecular mechanisms that lead to the acquisition of virulence, we can gain better insight into the pathogenic processes that underlie filovirus disease in humans. These processes, and the viral and/or cellular proteins that contribute to them, will make attractive targets for the development of novel therapeutics and counter-measures.
authors.affiliation: Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
authors.forename: Logan
authors.initials: L
authors.lastname: Banadyga
authors.affiliation: Bioinformatics and Computational Biosciences Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Dolan
authors.affiliation: Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA. Electronic address: ebiharah@niaid.nih.gov.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ebihara
mesh_terms: D000220:Adaptation, Biological; D000818:Animals; D006224:Cricetinae; D004195:Disease Models, Animal; D016563:Filoviridae / Q000235:genetics* / Q000472:pathogenicity*; D018702:Filoviridae Infections / Q000473:pathology* / Q000821:virology*; D006168:Guinea Pigs; D051379:Mice; D014774:Virulence
keywords: Ebola virus; Filovirus; Marburg virus; pathogenesis; rodent adaptation