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Volume 6 Supplement 3

AIDS Vaccine 2009

P16-41. Evidence for in vivo immune selection pressure exerted by HLA class I restricted CTL responses to anti-sense encoded HIV sequences

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Background

Past studies have suggested that certain portions of the integrated HIV-1 proviral genome can be transcribed in the anti-sense direction, resulting in novel viral protein products that may provide alternative targets for the host anti-viral immune response. Little is known whether immune responses exist against antisense HIV peptides, whether they can recognize HIV infected cells and whether CTL-driven escape mutations within antisense peptides may be detectable on a population level.

Methods

Anti-sense sequences with potential start codons (Methionine) that preceded well-conserved genome sequences of at least 50 nucleotide triplets without stop codon were identified in 261 aligned HIV whole-genome sequences. Plasma HIV gag, pol and nef sequences from >500 treatment-naive, chronic infected patients were analyzed for HLA class I allele-specific viral polymorphisms in all three possible reading frames in the anti-sense direction. A maximal false-discovery rate of 20% (q value < 0.2) was applied to correct for multiple tests. Polymorphisms in the anti-sense direction that affected the original coding sequence were excluded from study.

Results

Five potential anti-sense encoded proteins, including the previously described HIV anti-sense protein (ASP) were identified. Each putative protein sequence was synthesized as overlapping peptide set and was targeted by at least 2 individuals (range 2–22) of 40 HIV infected subjects tested. HLA-footprint analyses revealed 67 HLA-associated imprints (37 gag, 6 nef, 34 pol). For each imprint, the predicted epitopes were tested in individuals expressing the appropriate HLA allele. Several frequently-targeted antisense epitopes were identified.

Conclusion

CTL responses targeting anti-sense derived epitopes in HIV may be relatively common and may have an impact on viral evolution at the population level. Thus, T cell specificities to anti-sense encoded epitopes may be a biologically relevant mechanism contributing to immune control of HIV and may represent interesting vaccine immunogen candidates.

Author information

Correspondence to CT Berger.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Berger, C., Carlson, J., Brumme, C. et al. P16-41. Evidence for in vivo immune selection pressure exerted by HLA class I restricted CTL responses to anti-sense encoded HIV sequences. Retrovirology 6, P270 (2009). https://doi.org/10.1186/1742-4690-6-S3-P270

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Keywords

  • Proviral Genome
  • Putative Protein Sequence
  • Nucleotide Triplet
  • Antisense Peptide
  • Viral Protein Product