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Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus.

Publication ,  Journal Article
Song, H; Hora, B; Bhattacharya, T; Goonetilleke, N; Liu, MKP; Wiehe, K; Li, H; Iyer, SS; McMichael, AJ; Perelson, AS; Gao, F
Published in: PLoS One
2014

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.

Duke Scholars

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2014

Volume

9

Issue

7

Start / End Page

e102734

Location

United States

Related Subject Headings

  • Virus Replication
  • Sequence Analysis, DNA
  • Mutation, Missense
  • Molecular Sequence Data
  • Immune Evasion
  • Humans
  • HIV-1
  • Genome, Viral
  • Genetic Fitness
  • General Science & Technology
 

Citation

APA
Chicago
ICMJE
MLA
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Song, H., Hora, B., Bhattacharya, T., Goonetilleke, N., Liu, M. K. P., Wiehe, K., … Gao, F. (2014). 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, 9(7), e102734. https://doi.org/10.1371/journal.pone.0102734
Song, Hongshuo, Bhavna Hora, Tanmoy Bhattacharya, Nilu Goonetilleke, Michael K. P. Liu, Kevin Wiehe, Hui Li, et al. “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 9, no. 7 (2014): e102734. https://doi.org/10.1371/journal.pone.0102734.
Song H, Hora B, Bhattacharya T, Goonetilleke N, Liu MKP, Wiehe K, et al. 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. 2014;9(7):e102734.
Song, Hongshuo, et al. “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, vol. 9, no. 7, 2014, p. e102734. Pubmed, doi:10.1371/journal.pone.0102734.
Song H, Hora B, Bhattacharya T, Goonetilleke N, Liu MKP, Wiehe K, Li H, Iyer SS, McMichael AJ, Perelson AS, Gao F. 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. 2014;9(7):e102734.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2014

Volume

9

Issue

7

Start / End Page

e102734

Location

United States

Related Subject Headings

  • Virus Replication
  • Sequence Analysis, DNA
  • Mutation, Missense
  • Molecular Sequence Data
  • Immune Evasion
  • Humans
  • HIV-1
  • Genome, Viral
  • Genetic Fitness
  • General Science & Technology