HIV-1 capsids from B27/B57+ elite controllers escape Mx2 but are targeted by TRIM5α, leading to the induction of an antiviral state
Bibliographic record
Abstract
Elite controllers (ECs) are a rare subset of HIV-1 slow progressors characterized by prolonged viremia suppression.HLA alleles B27 and B57 promote the cytotoxic T lymphocyte (CTL)-mediated depletion of infected cells in ECs, leading to the emergence of escape mutations in the viral capsid (CA).Whether those mutations modulate CA detection by innate sensors and effectors is poorly known.Here, we investigated the targeting of CA from B27/B57 + individuals by cytosolic antiviral factors Mx2 and TRIM5α.Toward that aim, we constructed chimeric HIV-1 vectors using CA isolated from B27/B57 + or control subjects.HIV-1 vectors containing B27/B57 + -specific CA had increased sensitivity to TRIM5α but not to Mx2.Following exposure to those vectors, cells showed increased resistance against both TRIM5α-sensitive and -insensitive HIV-1 strains.Induction of the antiviral state did not require productive infection by the TRIM5α-sensitive virus, as shown using chemically inactivated virions.Depletion experiments revealed that TAK1 and Ubc13 were essential to the TRIM5α-dependent antiviral state.Accordingly, induction of the antiviral state was accompanied by the activation of NF-κB and AP-1 in THP-1 cells.Secretion of IFN-I was involved in the antiviral state in THP-1 cells, as shown using a receptor blocking antibody.This work identifies innate activation pathways that are likely to play a role in the natural resistance to HIV-1 progression in ECs. Author summarySome HIV-1-infected individuals show a natural capacity to control viral propagation.In individuals that have the HLA B27 or B57 allele, HIV-1 control is associated with mutations in viral proteins that arise as a result of immune pressure from cytotoxic T lymphocytes.HIV-1 capsid protein mutations found in these subjects render HIV-1 more sensitive to detection by TRIM5α, a cytoplasmic innate effector that targets retroviral capsids.We show here that HIV-1 bearing such mutations is restricted by TRIM5α but not by Mx2,
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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 | 0.001 |
| 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".