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Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation

Overview of attention for article published in Retrovirology, November 2014
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Title
Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation
Published in
Retrovirology, November 2014
DOI 10.1186/s12977-014-0101-0
Pubmed ID
Authors

Donglai Liu, Tao Zuo, Bhavna Hora, Hongshuo Song, Wei Kong, Xianghui Yu, Nilu Goonetilleke, Tanmoy Bhattacharya, Alan S Perelson, Barton F Haynes, Andrew J McMichael, Feng Gao

Abstract

BackgroundFitness costs and slower disease progression are associated with a cytolytic T lymphocyte (CTL) escape mutation T242N in Gag in HIV-1-infected individuals carrying HLA-B*57/5801 alleles. However, the impact of different context in diverse HIV-1 strains on the fitness costs due to the T242N mutation has not been well characterized. To better understand the extent of fitness costs of the T242N mutation and the repair of fitness loss through compensatory amino acids, we investigated its fitness impact in different transmitted/founder (T/F) viruses.ResultsThe T242N mutation resulted in various levels of fitness loss in four different T/F viruses. However, the fitness costs were significantly compromised by preexisting compensatory amino acids in (Isoleucine at position 247) or outside (glutamine at position 219) the CTL epitope. Moreover, the transmitted T242N escape mutant in subject CH131 was as fit as the revertant N242T mutant and the elimination of the compensatory amino acid I247 in the T/F viral genome resulted in significant fitness cost, suggesting the fitness loss caused by the T242N mutation had been fully repaired in the donor at transmission. Analysis of the global circulating HIV-1 sequences in the Los Alamos HIV Sequence Database showed a high prevalence of compensatory amino acids for the T242N mutation and other T cell escape mutations.ConclusionsOur results show that the preexisting compensatory amino acids in the majority of circulating HIV-1 strains could significantly compromise the fitness loss due to CTL escape mutations and thus increase challenges for T cell based vaccines.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 22 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 22 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 32%
Researcher 4 18%
Student > Bachelor 2 9%
Professor > Associate Professor 2 9%
Professor 2 9%
Other 3 14%
Unknown 2 9%
Readers by discipline Count As %
Agricultural and Biological Sciences 7 32%
Biochemistry, Genetics and Molecular Biology 5 23%
Medicine and Dentistry 3 14%
Physics and Astronomy 2 9%
Mathematics 1 5%
Other 1 5%
Unknown 3 14%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 20 November 2014.
All research outputs
#9,983,602
of 12,472,057 outputs
Outputs from Retrovirology
#634
of 715 outputs
Outputs of similar age
#189,600
of 282,320 outputs
Outputs of similar age from Retrovirology
#22
of 25 outputs
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