A precise excision of the complete Epstein-Barr virus genome in a plasmid based on a bacterial artificial chromosome

J Virol Methods. 2011 Sep;176(1-2):103-7. doi: 10.1016/j.jviromet.2011.06.015. Epub 2011 Jun 23.

Abstract

The Maxi-EBV is a bacterial artificial chromosome (BAC)-based plasmid that contains the complete Epstein-Barr virus (EBV) genome of 172 kb. This plasmid also carries an additional cassette of 11.5 kb in size for the expression of a mini F factor, selection markers and GFP. In the intracellular study of EBV infection based on the Maxi-EBV system, a parallel control that only contains this 11.5 kb vector is desirable but unavailable. In order to construct the vector in this approach, a clean deletion of the complete EBV genome from the Maxi-EBV was performed. This was achieved by homologous recombination using the bacteriophage λ Red system. Initially, an FRT-flanked kanamycin-resistance (kan) fragment of 1.4 kb with 61 bp homologies on the ends was introduced into the Maxi-EBV plasmid, replacing the 172-kb EBV genome. The kan gene was then removed by Flp/FRT excision. The results of identification demonstrated that the mutation was generated precisely. The results highlight the feasibility for a genome as large as 172 kb to be replaced by a greatly shorter fragment and for a much smaller vector backbone to be retrieved. Cell lines derived from the transfection of the vector will subsequently be appropriate controls in the related study.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteriophage lambda / enzymology
  • Cell Line
  • Chromosomes, Artificial, Bacterial / genetics*
  • Genetic Engineering / methods
  • Genetic Vectors
  • Genome, Viral / genetics*
  • Herpesvirus 4, Human / genetics*
  • Homologous Recombination*
  • Humans
  • Mice
  • Mice, Nude
  • Plasmids*
  • Sequence Deletion*
  • Transfection