Generation of biologically contained Ebola viruses

Peter Halfmann, Hyun Kim Jin, Hideki Ebihara, Takeshi Noda, Gabriele Neumann, Heinz Feldmann, Yoshihiro Kawaoka

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Ebola virus (EBOV), a public health concern in Africa and a potential biological weapon, is classified as a biosafety level-4 agent because of its high mortality rate and the lack of approved vaccines and antivirals. Basic research into the mechanisms of EBOV pathogenicity and the development of effective countermeasures are restricted by the current biosafety classification of EBOVs. We therefore developed biologically contained EBOV that express a reporter gene instead of the VP30 gene, which encodes an essential transcription factor. A Vero cell line that stably expresses VP30 provides this essential protein in trans and biologically confines the virus to its complete replication cycle in this cell line. This complementation approach is highly efficient because biologically contained EBOVs lacking the VP30 gene grow to titers similar to those obtained with wild-type virus. Moreover, EBOVs lacking the VP30 gene are indistinguishable in their morphology from wild-type virus and are genetically stable, as determined by sequence analysis after seven serial passages in VP30-expressing Vero cells. We propose that this system provides a safe means to handle EBOV outside a biosafety level-4 facility and will stimulate critical studies on the EBOV life cycle as well as large-scale screening efforts for compounds with activity against this lethal virus.

Original languageEnglish (US)
Pages (from-to)1129-1133
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number4
DOIs
StatePublished - Jan 29 2008

Keywords

  • Antiviral screening
  • Reverse genetics
  • Vaccine development

ASJC Scopus subject areas

  • General

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