title: Design and engineering of a transmissible antiviral defense.
abstract: BACKGROUND
  We propose, model, and implement a novel system of population-level intervention against a virus. One context is a treatment against a chronic infection such as HIV. The underlying principle is a form of virus 'wars' in which a benign, transmissible agent is engineered to protect against infection by and spread of a lethal virus. In our specific case, the protective agent consists of two entities, a benign virus and a gene therapy vector mobilized by the benign virus.
  
  
  RESULTS
  Numerical analysis of a mathematical model identified parameter ranges in which adequate, population-wide protection is achieved. The protective system was implemented and tested usingE. coli, bacteriophage M13 and a phagemid vector mobilized by M13 to block infection by the lethal phage T5. Engineering of M13 profoundly improved its dynamical properties for facilitating spread of the gene therapy vector. However, the gene therapy vector converts the host cell to resist T5 too slowly for protection on a time scale appropriate for T5.
  
  
  CONCLUSIONS
  Overall, there is a reasonable marriage between the mathematical model and the empirical system, suggesting that such models can be useful guides to the design of such systems even before the models incorporate most of the relevant biological details.
authors.affiliation: Department of Integrative Biology, University of Texas at Austin, Austin, 78712 TX USA ; Institute of Cellular and Molecular Biology, University of Texas at Austin, Austin, 78712 TX USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Paff
authors.affiliation: Department of Biological Sciences, University of Idaho, Moscow, 83843 ID USA.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Nuismer
authors.affiliation: Department of Molecular Biosciences, University of Texas at Austin, Austin, 78712 TX USA ; Institute of Cellular and Molecular Biology, University of Texas at Austin, Austin, 78712 TX USA ; Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, 78712 TX USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Ellington
authors.affiliation: Department of Molecular Biosciences, University of Texas at Austin, Austin, 78712 TX USA ; Institute of Cellular and Molecular Biology, University of Texas at Austin, Austin, 78712 TX USA.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Molineux
authors.affiliation: Department of Biological Sciences, University of Idaho, Moscow, 83843 ID USA.
authors.forename: Ryan H
authors.initials: RH
authors.lastname: May
authors.affiliation: Department of Integrative Biology, University of Texas at Austin, Austin, 78712 TX USA ; Institute of Cellular and Molecular Biology, University of Texas at Austin, Austin, 78712 TX USA ; Center for Computational Biology and Bioinformatics, University of Texas at Austin, Austin, 78712 TX USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Bull
keywords: Bacteriophage; Genetic engineering; Transmissible vaccine; Virus