title: Reverse genetics systems as tools for the development of novel therapies against filoviruses.
abstract: Filoviruses cause severe hemorrhagic fevers with case fatality rates of up to 90%, for which no antivirals are currently available. Their categorization as biosafety level 4 agents restricts work with infectious viruses to a few maximum containment laboratories worldwide, which constitutes a significant obstacle for the development of countermeasures. Reverse genetics facilitates the generation of recombinant filoviruses, including reporter-expressing viruses, which have been increasingly used for drug screening and development in recent years. Further, reverse-genetics based lifecycle modeling systems allow modeling of the filovirus lifecycle without the need for a maximum containment laboratory and have recently been optimized for use in high-throughput assays. The availability of these reverse genetics-based tools will significantly improve our ability to find novel antivirals against filoviruses.
authors.affiliation: Division of Intramural Research, Laboratory of Virology, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hoenen
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D029043:Ebolavirus / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D016563:Filoviridae / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D018702:Filoviridae Infections / Q000188:drug therapy*; D016679:Genome, Viral; D006801:Humans; D008826:Microbial Sensitivity Tests; D008962:Models, Theoretical; D059386:Reverse Genetics / Q000379:methods*; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents
keywords: Ebola virus; antiviral screening; filoviruses; marburg virus; minigenome system; recombinant virus; reporter-expressing virus; reverse genetics; transcription and replication-competent particle system