Adaptability costs in immune escape variants of vesicular stomatitis virus.
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.
Novella
Isabel S
IS
Department of Microbiology and Immunology, Medical College of Ohio, 3055 Arlington Avenue Toledo, OH 43614, USA. isabel@mco.edu
Gilbertson
Dorothy L
DL
Borrego
Belen
B
Domingo
Esteban
E
Holland
John J
JJ
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
D000914:Antibodies, Viral; C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins