Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus.
Immune escape mutations that revert back to the consensus sequence frequently occur in newly HIV-1-infected individuals and have been thought to render the viruses more fit. However, their impact on viral fitness and their interaction with other immune escape mutations have not been evaluated in the...
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| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0102734&type=printable |
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| author | Hongshuo Song Bhavna Hora Tanmoy Bhattacharya Nilu Goonetilleke Michael K P Liu Kevin Wiehe Hui Li Shilpa S Iyer Andrew J McMichael Alan S Perelson Feng Gao |
| author_facet | Hongshuo Song Bhavna Hora Tanmoy Bhattacharya Nilu Goonetilleke Michael K P Liu Kevin Wiehe Hui Li Shilpa S Iyer Andrew J McMichael Alan S Perelson Feng Gao |
| author_sort | Hongshuo Song |
| collection | DOAJ |
| description | Immune escape mutations that revert back to the consensus sequence frequently occur in newly HIV-1-infected individuals and have been thought to render the viruses more fit. However, their impact on viral fitness and their interaction with other immune escape mutations have not been evaluated in the background of their cognate transmitted/founder (T/F) viral genomes. To precisely determine the role of reversion mutations, we introduced reversion mutations alone or together with CD8+ T cell escape mutations in their unmodified cognate T/F viral genome and determined their impact on viral fitness in primary CD4+ T cells. Two reversion mutations, V247I and I64T, were identified in Gag and Tat, respectively, but neither had measurable effect on the fitness of their cognate T/F virus. The V247I and G248A mutations that were detected before and concurrently with the potent T cell escape mutation T242N, respectively, were selected by early T cell responses. The V247I or the G248A mutation alone partially restored the fitness loss caused by the T242N mutation. Together they could fully restore the fitness of the T242N mutant to the T/F level. These results demonstrate that the fitness loss caused by a T cell escape mutation could be compensated by preexisting or concurrent reversion and other T cell escape mutations. Our findings indicate that the overall viral fitness is modulated by the complex interplay among T cell escape, compensatory and reversion mutations to maintain the balance between immune escape and viral replication capacity. |
| format | Article |
| id | doaj-art-c29a8a2f8ba94141b1400ac1d51a81bc |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-c29a8a2f8ba94141b1400ac1d51a81bc2025-08-20T03:46:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0197e10273410.1371/journal.pone.0102734Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus.Hongshuo SongBhavna HoraTanmoy BhattacharyaNilu GoonetillekeMichael K P LiuKevin WieheHui LiShilpa S IyerAndrew J McMichaelAlan S PerelsonFeng GaoImmune escape mutations that revert back to the consensus sequence frequently occur in newly HIV-1-infected individuals and have been thought to render the viruses more fit. However, their impact on viral fitness and their interaction with other immune escape mutations have not been evaluated in the background of their cognate transmitted/founder (T/F) viral genomes. To precisely determine the role of reversion mutations, we introduced reversion mutations alone or together with CD8+ T cell escape mutations in their unmodified cognate T/F viral genome and determined their impact on viral fitness in primary CD4+ T cells. Two reversion mutations, V247I and I64T, were identified in Gag and Tat, respectively, but neither had measurable effect on the fitness of their cognate T/F virus. The V247I and G248A mutations that were detected before and concurrently with the potent T cell escape mutation T242N, respectively, were selected by early T cell responses. The V247I or the G248A mutation alone partially restored the fitness loss caused by the T242N mutation. Together they could fully restore the fitness of the T242N mutant to the T/F level. These results demonstrate that the fitness loss caused by a T cell escape mutation could be compensated by preexisting or concurrent reversion and other T cell escape mutations. Our findings indicate that the overall viral fitness is modulated by the complex interplay among T cell escape, compensatory and reversion mutations to maintain the balance between immune escape and viral replication capacity.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0102734&type=printable |
| spellingShingle | Hongshuo Song Bhavna Hora Tanmoy Bhattacharya Nilu Goonetilleke Michael K P Liu Kevin Wiehe Hui Li Shilpa S Iyer Andrew J McMichael Alan S Perelson Feng Gao Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. PLoS ONE |
| title | Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. |
| title_full | Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. |
| title_fullStr | Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. |
| title_full_unstemmed | Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. |
| title_short | Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. |
| title_sort | reversion and t cell escape mutations compensate the fitness loss of a cd8 t cell escape mutant in their cognate transmitted founder virus |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0102734&type=printable |
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