New Challenges, New Commitments: 19th Annual Canadian Conference on HIV/AIDS Research
Bibliographic record
Abstract
CD8 T-cells restricted by protective HLA class I alleles mount early and robust responses to the HIV Gag protein, and may select for escape mutations that impair Gag function and reduce viral replication capacity.However, the extent to which early immune responses drive alterations in viral fitness and the implications of this on disease progression remain incompletely understood.We used a recombinant viral method to investigate whether immune-associated fitness defects are detectable during acute/early infection.NL4-3 viruses encoding patient HIV RNA-derived Gag-Protease sequences were generated from a cohort of individuals (N=67) enrolled a median of 52 [IQR 31-72] days following estimated date of infection.Viral replication capacity (RC) was assessed using an established GFP reporter T-cell assay and normalized to wild-type NL4-3.Recombinant viruses derived from individuals expressing a protective HLA allele (defined as B13, 27, 57, 5801; N=20) displayed significantly lower RC compared to those from individuals lacking a protective allele (N=47) (mean RC 0.89 vs. 1.02, respectively, p<0.0001).No significant correlation was observed between RC and viral load or CD4 count during untreated clinical follow-up (median 24 months).Analysis of plasma HIV RNA Gag sequences revealed a significant inverse correlation between the total number of HLA-associated mutations and RC.This was most notable for HLA-B alleles, and suggests a dose-dependent effect of early escape mutations that compromised fitness.Results support the hypothesis that early CD8 responses restricted by protective HLA class I alleles select for escape mutations in Gag that compromise its function.Although the selection of compensatory mutations may partially rescue these effects, early "hits" to viral fitness may have long-lasting implications for attenuating the disease course.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.011 | 0.008 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.003 | 0.002 |
| Science and technology studies | 0.004 | 0.004 |
| Scholarly communication | 0.009 | 0.005 |
| Open science | 0.003 | 0.005 |
| Research integrity | 0.006 | 0.007 |
| Insufficient payload (model declined to judge) | 0.094 | 0.030 |
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 source (direct Gemma or distilled Codex), 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".