Genetic variations in the host dependency factors ALCAM and TPST2 impact HIV-1 disease progression
Bibliographic record
Abstract
OBJECTIVES: Recently, the activated leukocyte cell adhesion molecule (ALCAM) and tyrosylprotein sulfotransferase 2 (TPST2) have been identified as important host dependency factors (HDFs) for in-vitro HIV-1 replication. To determine whether these genes play a role in HIV-1 pathogenesis, we analysed whether naturally occurring genetic variations were associated with the clinical course of infection. DESIGN/METHODS: Single nucleotide polymorphisms (SNPs) in ALCAM and TPST2 were analysed in a cohort of 304 HIV-1-infected men who have sex with men and survival analysis was used to determine their effect on the outcome of untreated HIV-1 infection. Flowcytometry was used to determine the effect of SNPs on CD4 T-cell activation prior to HIV-1 infection and 1 and 5 years after infection. In-vitro HIV-1 infections were performed to analyse the effect of the SNPs on HIV-1 replication. RESULTS: We observed that the minor allele of rs1344861 in ALCAM was associated with accelerated disease progression, whereas the minor allele of rs9613199 in TPST2 was associated with delayed disease progression. In-vitro infection assays did not demonstrate any differences in HIV-1 replication associated with rs9613199. However, the increase in CD4 T-cell immune activation levels during HIV-1 infection was less pronounced in infected individuals homozygous for rs9613199, which is in agreement with delayed disease progression. CONCLUSION: Our data demonstrate that ALCAM and TPST2 play a role in HIV-1 pathogenesis. SNPs in these genes, without known functional implications, had a major effect on disease progression, and therefore, these HDFs may be attractive and effective targets for new treatment strategies.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".