title: HSPA5 is an essential host factor for Ebola virus infection.
abstract: Development of novel strategies targeting the highly virulent ebolaviruses is urgently required. A proteomic study identified the ER chaperone HSPA5 as an ebolavirus-associated host protein. Here, we show using the HSPA5 inhibitor (-)- epigallocatechin gallate (EGCG) that the chaperone is essential for virus infection, thereby demonstrating a functional significance for the association. Furthermore, in vitro and in vivo gene targeting impaired viral replication and protected animals in a lethal infection model. These findings demonstrate that HSPA5 is vital for replication and can serve as a viable target for the design of host-based countermeasures.
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702-5011, USA.
authors.forename: St Patrick
authors.initials: SP
authors.lastname: Reid
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702-5011, USA.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Shurtleff
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702-5011, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Costantino
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702-5011, USA.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Tritsch
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702-5011, USA.
authors.forename: Cary
authors.initials: C
authors.lastname: Retterer
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702-5011, USA.
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Spurgers
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702-5011, USA. Electronic address: sina.bavari@amedd.army.mil.
authors.forename: Sina
authors.initials: S
authors.lastname: Bavari
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D029043:Ebolavirus / Q000187:drug effects / Q000502:physiology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D019142:Hemorrhagic Fever, Ebola / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D008810:Mice, Inbred C57BL; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D002392:Catechin; C045651:epigallocatechin gallate
keywords: Antiviral; Ebolavirus; HSPA5