title: Ebola Virus Glycoprotein Promotes Enhanced Viral Egress by Preventing Ebola VP40 From Associating With the Host Restriction Factor BST2/Tetherin.
abstract: BACKGROUND
  BST2/tetherin is an innate immune molecule with the unique ability to restrict the egress of human immunodeficiency virus (HIV) and other enveloped viruses, including Ebola virus (EBOV). Coincident with this discovery was the finding that the HIV Vpu protein down-regulates BST2 from the cell surface, thereby promoting viral release. Evidence suggests that the EBOV envelope glycoprotein (GP) also counteracts BST2, although the mechanism is unclear.
  
  
  RESULTS
  We find that total levels of BST2 remain unchanged in the presence of GP, whereas surface BST2 is significantly reduced. GP is known to sterically mask surface receptors via its mucin domain. Our evaluation of mutant GP molecules indicate that masking of BST2 by GP is probably responsible for the apparent surface BST2 down-regulation; however, this masking does not explain the observed virus-like particle egress enhancement. We discovered that VP40 coimmunoprecipitates and colocalizes with BST2 in the absence but not in the presence of GP.
  
  
  CONCLUSIONS
  These results suggest that GP may overcome the BST2 restriction by blocking an interaction between VP40 and BST2. Furthermore, we have observed that GP may enhance BST2 incorporation into virus-like particles. Understanding this novel EBOV immune evasion strategy will provide valuable insights into the pathogenicity of this deadly pathogen.
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton.
authors.forename: Jean K
authors.initials: JK
authors.lastname: Gustin
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton.
authors.forename: Ying
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton.
authors.forename: Ashlee V
authors.initials: AV
authors.lastname: Moses
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton.
authors.forename: Janet L
authors.initials: JL
authors.lastname: Douglas
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D002460:Cell Line; D015536:Down-Regulation / Q000502:physiology; D029043:Ebolavirus / Q000378:metabolism* / Q000472:pathogenicity*; D058851:GPI-Linked Proteins / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D009077:Mucins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D011956:Receptors, Cell Surface / Q000378:metabolism; D014763:Viral Matrix Proteins; D014764:Viral Proteins / Q000378:metabolism; D057074:Virus Release / Q000502:physiology*; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D006023:Glycoproteins; D009077:Mucins; D011956:Receptors, Cell Surface; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C080981:VP40 protein, virus
keywords: BST2; Ebola GP; Ebola VP40; Ebola virus; HIV; host immune restriction; tetherin; viral egress
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