P16-41. Evidence for in vivo immune selection pressure exerted by HLA class I restricted CTL responses to anti-sense encoded HIV sequences
Bibliographic record
Abstract
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. 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. 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. 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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".