Susceptibility of HIV Type 1 to the Fusion Inhibitor T‐20 Is Reduced on Insertion of Host Intercellular Adhesion Molecule 1 in the Virus Membrane
Bibliographic record
Abstract
BACKGROUND: T-20 is a synthetic peptide that targets and blocks the entry of human immunodeficiency virus (HIV)-1 inside target cells. Data from clinical studies have shown that primary HIV-1 variants display a broad range of susceptibilities to T-20 that are mainly caused by mutations in the N-terminal heptad repeat of gp41 and by other determinants, such as envelope and coreceptor affinity, coreceptor specificity, and receptor density. We investigated whether sensitivity to this drug is affected by the incorporation of intercellular adhesion molecule (ICAM)-1 in HIV-1. METHODS: We used laboratory isolates of HIV-1 (X4- and R5-tropic) either lacking or bearing ICAM-1 and clinical variants. RESULTS: We demonstrate that ICAM-1-bearing virions are more resistant to T-20 than are isogenic HIV-1 particles without it. This effect is lost when ICAM-1/leukocyte function antigen-1 interactions are blocked by antibody. The mechanism through which virus-anchored host ICAM-1 is acting seems to be a reduction of the kinetic window during which the viral envelope is sensitive to T-20. CONCLUSIONS: Altogether, these results demonstrate that the insertion of host-derived ICAM-1 into HIV-1 represents another factor that affects virus sensitivity to the entry inhibitor. These findings have potential implications for the therapeutic use of T-20.
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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 | 0.000 | 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) | 0.002 | 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 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".