Role of EXT1 and glycosaminoglycans in the early stage of filovirus entry

Aileen O'Hearn, Minxiu Wang, Han Cheng, Calli M. Lear-Rooney, Katie Koning, Emily Rumschlag-Booms, Elizabeth Varhegyi, Gene Olinger, Lijun Rong

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Filoviruses, including both Ebola virus (EBOV) and Marburg virus (MARV), can infect humans and other animals, causing hemorrhagic fever with a high mortality rate. Entry of these viruses into the host is mediated by a single filoviral glycoprotein (GP). GP is composed of two subunits: GP1, which is responsible for attachment and binding to receptor(s) on susceptible cells, and GP2, which mediates viral and cell membrane fusion. Although numerous host factors have been implicated in the entry process, the initial attachment receptor(s) has not been well defined. In this report, we demonstrate that exostosin 1 (EXT1), which is involved in biosynthesis of heparan sulfate (HS), plays a role in filovirus entry. Expression knockdown of EXT1 by small interfering RNAs (siRNAs) impairs GP-mediated pseudoviral entry and that of infectious EBOV and MARV in tissue cultured cells. Furthermore, HS, heparin, and other related glycosaminoglycans (GAGs), to different extents, can bind to and block GP-mediated viral entry and that of infectious filoviruses. These results strongly suggest that HS and other related GAGs are attachment receptors that are utilized by filoviruses for entry and infection. These GAGs may have therapeutic potential in treating EBOV- and MARV-infected patients.

Original languageEnglish (US)
Pages (from-to)5441-5449
Number of pages9
JournalJournal of virology
Volume89
Issue number10
DOIs
StatePublished - 2015
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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