title: Directed Evolution of Adenoviruses.
abstract: The ability to evolve viruses in cell culture in the face of selective pressure is an invaluable method to elucidate the molecular mechanisms of synthetic or natural antivirals, expand tropism, or alter virulence. Recently, mutations to the human adenovirus polymerase that reduce replicative fidelity were described, and we have incorporated one of these mutations into the pol gene of a conditionally replicating human adenovirus serotype 5 (HAdV-5)-based vector (Uil et al., Nucleic Acids Res 39:e30, 2011; Myers et al., J Virol 87:6047-6050, 2013). Here, we describe methods to evolve this virus (HAdV-5.polF421Y) under selective pressure from antivirals to identify their mechanisms of action.
authors.affiliation: Department of Microbiology, University of Washington, Box 357735 1705 NE Pacific Street, Seattle, WA, 98195, USA. jgsmith2@uw.edu.
authors.forename: Jason G
authors.initials: JG
authors.lastname: Smith
mesh_terms: D000260:Adenoviruses, Human / Q000187:drug effects / Q000235:genetics / Q000254:growth & development*; D000998:Antiviral Agents / Q000494:pharmacology*; D019020:Directed Molecular Evolution; D024882:Drug Resistance, Viral; D015684:Gene Products, pol / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D009154:Mutation; D018523:Tropism
chemical_list: D000998:Antiviral Agents; D015684:Gene Products, pol
keywords: Adenovirus; Antiviral; Evolution; Mutator