Chinese hamster ovary cell lines selected for resistance to ebolavirus glycoprotein mediated infection are defective for NPC1 expression

Kathleen M. Haines, Nathan H. Vande Burgt, Joseph R. Francica, Rachel L. Kaletsky, Paul Bates

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Ebolavirus causes severe hemorrhagic fever in humans and non-human primates. Entry of ebolavirus is mediated by the viral glycoprotein, GP; however, the required host factors have not been fully elucidated. A screen utilizing a recombinant Vesicular Stomatitis Virus (VSV) encoding Zaire ebolavirus GP identified four Chinese Hamster Ovary (CHO) cell lines resistant to GP-mediated viral entry. Susceptibility to vectors carrying SARS coronavirus S or VSV-G glycoproteins suggests that endocytic and processing pathways utilized by other viruses are intact in these cells. A cathepsin-activated form of the ebolaviral glycoprotein did not overcome the entry restriction, nor did expression of several host factors previously described as important for ebolavirus entry. Conversely, expression of the recently described ebolavirus host entry factor Niemann-Pick Type C1 (NPC1) restored infection. Resistant cells encode distinct mutations in the NPC1 gene, resulting in loss of protein expression. These studies reinforce the importance of NPC1 for ebolavirus entry.

Original languageEnglish (US)
Pages (from-to)20-28
Number of pages9
JournalVirology
Volume432
Issue number1
DOIs
StatePublished - Oct 10 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Virology

Keywords

  • CHO-K1
  • Ebolavirus
  • Ebolavirus GP
  • Host factor
  • Niemann-Pick Type C1-NPC1
  • Viral entry
  • Viral glycoprotein

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