title: Virus wars: using one virus to block the spread of another.
abstract: The failure of traditional interventions to block and cure HIV infections has led to novel proposals that involve treating infections with therapeutic viruses-infectious viruses that specifically inhibit HIV propagation in the host. Early efforts in evaluating these proposals have been limited chiefly to mathematical models of dynamics, for lack of suitable empirical systems. Here we propose, develop and analyze an empirical system of a therapeutic virus that protects a host cell population against a lethal virus. The empirical system uses E. coli bacteria as the host cell population, an RNA phage as the lethal virus and a filamentous phage as the therapeutic virus. Basic dynamic properties are established for each virus alone and then together. Observed dynamics broadly agree with those predicted by a computer simulation model, although some differences are noted. Two cases of dynamics are contrasted, differing in whether the therapeutic virus is introduced before the lethal virus or after the lethal virus. The therapeutic virus increases in both cases but by different mechanisms. With the therapeutic virus introduced first, it spreads infectiously without any appreciable change in host dynamics. With the therapeutic virus introduced second, host abundance is depressed at the time therapy is applied; following an initial period of therapeutic virus spread by infection, the subsequent rise of protection is through reproduction by hosts already protected. This latter outcome is due to inheritance of the therapeutic virus state when the protected cell divides. Overall, the work establishes the feasibility and robustness to details of a viral interference using a therapeutic virus.
authors.affiliation: Department of Integrative Biology, University of Texas, Austin, TX, United States; The Institute for Cellular and Molecular Biology, University of Texas, Austin, TX, United States.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Paff
authors.affiliation: Department of Biological Sciences, University of Idaho , Moscow , ID , United States.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Nuismer
authors.affiliation: Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, United States; The Institute for Cellular and Molecular Biology, University of Texas, Austin, TX, United States; Center for Systems, Biology, University of Texas at Austin, Austin, TX, United States.
authors.forename: Andrew
authors.initials: A
authors.lastname: Ellington
authors.affiliation: Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, United States; The Institute for Cellular and Molecular Biology, University of Texas, Austin, TX, United States.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Molineux
authors.affiliation: Department of Integrative Biology, University of Texas, Austin, TX, United States; The Institute for Cellular and Molecular Biology, University of Texas, Austin, TX, United States; Center for Computational Biology and Bioinformatics, University of Texas, Austin, TX, United States.
authors.forename: James J
authors.initials: JJ
authors.lastname: Bull
keywords: Bacteriophage; Gene therapy; Infectious vaccine; Intervention; Mathematical model; Population dynamics; Vaccine alternative