The Ebola virus glycoprotein mediates entry via a non-classical dynamin-dependent macropinocytic pathway

Nirupama Mulherkar, Matthijs Raaben, Juan Carlos de la Torre, Sean P. Whelan, Kartik Chandran

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

Ebola virus (EBOV) has been reported to enter cultured cell lines via a dynamin-2-independent macropinocytic pathway or clathrin-mediated endocytosis. The route(s) of productive EBOV internalization into physiologically relevant cell types remain unexplored, and viral-host requirements for this process are incompletely understood. Here, we use electron microscopy and complementary chemical and genetic approaches to demonstrate that the viral glycoprotein, GP, induces macropinocytic uptake of viral particles into cells. GP's highly-glycosylated mucin domain is dispensable for virus-induced macropinocytosis, arguing that interactions between other sequences in GP and the host cell surface are responsible. Unexpectedly, we also found a requirement for the large GTPase dynamin-2, which is proposed to be dispensable for several types of macropinocytosis. Our results provide evidence that EBOV uses an atypical dynamin-dependent macropinocytosis-like entry pathway to enter Vero cells, adherent human peripheral blood-derived monocytes, and a mouse dendritic cell line.

Original languageEnglish
Pages (from-to)72-83
Number of pages12
JournalVirology
Volume419
Issue number2
DOIs
StatePublished - Oct 25 2011
Externally publishedYes

Keywords

  • Antigen presenting cells
  • Dendritic cells
  • Dynamin
  • Ebola virus
  • Endocytosis
  • Filovirus
  • Glycoprotein
  • Macropinocytosis
  • Monocytes
  • Pak-1
  • Vesicular stomatitis virus
  • Viral entry
  • Viral infection
  • Virus-like particles

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