title: Directed evolution of mutator adenoviruses resistant to antibody neutralization.
abstract: We incorporated a previously identified mutation that reduces the fidelity of the DNA polymerase into a human adenovirus vector. Using this mutator vector, we demonstrate rapid selection of resistance to a neutralizing anti-hexon monoclonal antibody due to a G434D mutation in hexon that precludes antibody binding. Since mutator adenoviruses can accumulate compound mutations that are unattainable using traditional random mutagenesis techniques, this approach will be valuable to the study of antivirals and host factor interactions.
authors.affiliation: University of Washington School of Medicine, Seattle, Washington, USA.
authors.forename: Nicolle D
authors.initials: ND
authors.lastname: Myers
authors.forename: Ksenia V
authors.initials: KV
authors.lastname: Skorohodova
authors.forename: Anshu P
authors.initials: AP
authors.lastname: Gounder
authors.forename: Jason G
authors.initials: JG
authors.lastname: Smith
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics* / Q000254:growth & development / Q000276:immunology*; D019943:Amino Acid Substitution; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D019020:Directed Molecular Evolution; D005827:Genetics, Microbial / Q000379:methods; D006801:Humans; D020125:Mutation, Missense; D019562:Viral Load; D014773:Virology / Q000379:methods
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; C018315:hexon capsid protein, Adenovirus