Ebola Virus Glycoprotein Promotes Enhanced Viral Egress by Preventing Ebola VP40 from Associating with the Host Restriction Factor BST2/Tetherin

Jean K. Gustin, Ying Bai, Ashlee V. Moses, Janet L. Douglas

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)S181-S190
JournalJournal of Infectious Diseases
Volume212
DOIs
StatePublished - Oct 1 2015

Keywords

  • BST2
  • Ebola GP
  • Ebola VP40
  • Ebola virus
  • HIV
  • host immune restriction
  • tetherin
  • viral egress

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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