title: Adaptability costs in immune escape variants of vesicular stomatitis virus.
abstract: We have used vesicular stomatitis virus (VSV) to determine the cost of antiserum resistance during escape from a polyclonal immune response. Replication of VSV in the presence of polyclonal antiserum resulted in the selection of antibody-escape mutants, as shown by increased fitness in the presence of antiserum and by increased resistance to neutralization. However, resistance came at a cost of overall fitness loss in the BHK-21 host cells. Sequencing of the surface G glycoprotein showed that two to four mutations were fixed in each population, most of which mapped in the A1 and A2 antigenic sites. Selected resistant populations were passaged as large populations in BHK-21 cells under constant conditions, which would normally lead to fitness increases. Nevertheless, many of the populations showed little or no sign of recovery, although the resistant phenotype was maintained. These results suggest that while antiserum resistance can develop, it may come at a cost in fitness and further limitations in the adaptability of the populations.
authors.affiliation: Department of Microbiology and Immunology, Medical College of Ohio, 3055 Arlington Avenue Toledo, OH 43614, USA. isabel@mco.edu
authors.forename: Isabel S
authors.initials: IS
authors.lastname: Novella
authors.forename: Dorothy L
authors.initials: DL
authors.lastname: Gilbertson
authors.forename: Belen
authors.initials: B
authors.lastname: Borrego
authors.forename: Esteban
authors.initials: E
authors.lastname: Domingo
authors.forename: John J
authors.initials: JJ
authors.lastname: Holland
mesh_terms: D000818:Animals; D000914:Antibodies, Viral; D002460:Cell Line; D006224:Cricetinae; D014644:Genetic Variation; D005838:Genotype; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D018448:Models, Immunological; D009154:Mutation; D009500:Neutralization Tests; D010641:Phenotype; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics* / Q000276:immunology* / Q000502:physiology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins