title: The multifunctional Ebola virus VP40 matrix protein is a promising therapeutic target.
abstract: The highly virulent nature of Ebola virus, evident from the 2014 West African pandemic, highlights the need to develop vaccines or therapeutic agents that limit the pathogenesis and spread of this virus. While vaccines represent an obvious approach, targeting virus interactions with host proteins that critically regulate the virus lifecycle also represent important therapeutic strategies. Among Ebola virus proteins at this critical interface is its matrix protein, VP40, which is abundantly expressed during infection and plays a number of critical roles in the viral lifecycle. In addition to regulating viral transcription, VP40 coordinates virion assembly and budding from infected cells. Details of the molecular mechanisms underpinning these essential functions are currently being elucidated, with a particular emphasis on its interactions with host proteins that control virion assembly and egress. This review focuses on the strategies geared toward developing novel therapeutic agents that target VP40-specific control of host functions critical to virion transcription, assembly and egress.
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Madara
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Ziying
authors.initials: Z
authors.lastname: Han
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Gordon
authors.initials: G
authors.lastname: Ruthel
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Freedman
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Harty
keywords: CTD; ESCRT; Ebola; L-domain; NTD; VLPs; VP40; antiviral; filovirus; oligomerization; therapeutic agent; viral budding; virus-like particles