Host restriction factor SAMHD1 limits human T-cell leukemia virus (HTLV-1) infection of primary monocytes via the innate immune sensor STING
Bibliographic record
Abstract
Human T-lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T cell leukemia (ATL) and other HTLV-1 associated neurological disorders. Unlike most retroviruses, cell-free HTLV-1 virions are poorly infectious and do not stably infect its primary CD4+ T lymphocyte target. However, HTLV-1 efficiently infects cells of the myeloid lineage, leading to productive infection of myeloid cells. Here, we investigate the mechanisms underlying monocyte infection by HTLV-1 and demonstrate that HTLV-1 infection induced apoptosis of monocytes in a SAMHD1-dependent manner. SAMHD1, a deoxynucleoside triphosphate triphosphohydrolase, functions as a restriction factor that limits HIV-1 replication by reducing the availability of deoxynucleosidetriphosphates (dNTPs) required for reverse transcription. RNAi-mediated silencing of SAMHD1 inhibited monocyte apoptosis, while addition of exogenous dNTPs, or pre-treatment with azidothymidine (AZT) to block reverse transcription also inhibited apoptosis. To investigate a role for reverse transcription intermediates (RTI) in triggering apoptosis, a biotinylated 90 nucleotide RTI from the U5 region of HTLV-1 was introduced into monocytes; strikingly, the biotinylated RTI induced apoptosis and bound to the DNA sensor STING - which mediates the antiviral response via IRF3 activation. We further demonstrated that STING-mediated apoptosis in infected monocytes required the generation of a pro-apoptotic complex between IRF3 and the Bcl-2 protein Bax. These studies provide a mechanistic explanation for HTLV-1 abortive infection of monocytes and report a link between SAMHD1 restriction of reverse transcription, sensing of retroviral reverse transcription intermediates by STING, and the initiation of IRF3-Bax driven apoptosis.
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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) | 0.001 | 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".