Author: Kevin W. Graepel; Maria L. Agostini; Xiaotao Lu; Nicole R. Sexton; Mark R. Denison
Title: Fitness barriers limit reversion of a proofreading-deficient coronavirus Document date: 2019_4_26
ID: 8pr10j88_6
Snippet: suggesting that these two variants are less fit than WT-ExoN-DE and demonstrating that 136 reversion by 1nt mutation is readily accessible. To test whether the 3nt or 2nt mutants would 137 revert more rapidly than ExoN-AA (4nt), we passaged three lineages of each mutant 10 times at (Table 1 ). In contrast, the 2nt ExoN-AE contained WT-revertants by P2 145 in all lineages at MOI = 0.5 PFU/cell and by P8 in one lineage at MOI = 0.01 PFU/cell. Once .....
Document: suggesting that these two variants are less fit than WT-ExoN-DE and demonstrating that 136 reversion by 1nt mutation is readily accessible. To test whether the 3nt or 2nt mutants would 137 revert more rapidly than ExoN-AA (4nt), we passaged three lineages of each mutant 10 times at (Table 1 ). In contrast, the 2nt ExoN-AE contained WT-revertants by P2 145 in all lineages at MOI = 0.5 PFU/cell and by P8 in one lineage at MOI = 0.01 PFU/cell. Once 146 observed, WT-revertants dominated the ExoN-AE population for the remaining passages. These 147 data indicate that at least one 2nt mutation pathway can lead to full reversion in tissue culture. 148
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