title: Biochemical Basis for Increased Activity of Ebola Glycoprotein in the 2013-16 Epidemic.
abstract: Ebola virus (EBOV) infection is characterized by sporadic outbreaks caused by zoonotic transmission. Fixed changes in amino acid sequence, such as A82V in the EBOV glycoprotein (GP) that occurred early in the 2013-16 epidemic, are suspected to confer a selective advantage to the virus. We used biochemical assays of GP function to show that A82V, as well as a polymorphism in residue 544 identified in other outbreaks, enhances infection by decreasing the threshold for activation of membrane fusion activity triggered by the host factors cathepsin B and Niemann-Pick C1. Importantly, the increase in infectivity comes with the cost of decreased virus stability. Thus, emergence of a virus GP with altered properties that can affect transmission and virulence may have contributed to the severity and scope of the 2013-16 EBOV epidemic.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
authors.forename: May K
authors.initials: MK
authors.lastname: Wang
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Lim
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Soo Mi
authors.initials: SM
authors.lastname: Lee
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA. Electronic address: jcunningham@rics.bwh.harvard.edu.
authors.forename: James M
authors.initials: JM
authors.lastname: Cunningham
mesh_terms: D019943:Amino Acid Substitution; D002352:Carrier Proteins / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism; D029043:Ebolavirus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D058872:Epidemics; D019142:Hemorrhagic Fever, Ebola / Q000453:epidemiology* / Q000821:virology*; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism*; D000077296:Niemann-Pick C1 Protein; D012641:Selection, Genetic; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D014774:Virulence; D053586:Virus Internalization
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D050505:Mutant Proteins; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein; D014759:Viral Envelope Proteins; C113189:envelope glycoprotein, Ebola virus; C533912:CTSB protein, human; D002401:Cathepsin B
keywords: Ebola; Makona; NPC1; West African outbreak; glycoprotein; membrane fusion; stability; virus infection