Design and engineering of a transmissible antiviral defense

Matthew L. Paff, Scott L. Nuismer, Andrew D. Ellington, Ian J. Molineux, Ryan H. May, James J. Bull

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. Numerical analysis of a mathematical model identified parameter ranges in which adequate, population-wide protection is achieved. The protective system was implemented and tested using E. 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. 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.