Suppression of Human T-cell Leukemia Virus I Gene Expression by Pokeweed Antiviral Protein
Bibliographic record
Abstract
Human T-cell leukemia virus I (HTLV-I) is a deltaretrovirus that is the causative agent of adult T-cell leukemia and the neurological disorder HTLV-I-associated myelopathy/tropical spastic paraparesis. Currently, no effective antiretroviral treatment options are available to restrict the development of diseases associated with the virus. In this work, we investigated the activity of pokeweed antiviral protein (PAP) on HTLV-I, when expressed from a proviral clone in 293T cells or in an HTLV-I immortalized cell line. PAP is a plant-derived N-glycosidase that exhibits antiviral activity against a number of viruses; however, its mode of action has not been clearly defined. Here, we describe the mechanism by which PAP inhibited production of HTLV-I. We show that PAP depurinated nucleotides within the gag open reading frame and suppressed the synthesis of viral proteins in part by decreasing the translational efficiency of HTLV-I gag/pol mRNA. Observed reduction in levels of viral mRNAs were not due to enhanced degradation; rather, decreased amounts of viral transactivator protein, Tax, led to feed-back inhibition of transcription from the viral promoter. Therefore, PAP efficiently suppressed HTLV-I gene expression at both translational and transcriptional levels, resulting in substantially diminished virus production. Significantly, no changes in viability or rates of cellular transcription or translation were observed in cells expressing PAP, indicating that this protein was not toxic. Antiviral activity, together with the absence of cytotoxicity, supports further investigation of this enzyme as a novel therapeutic agent against the progression of HTLV-I infection.
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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) | 0.000 | 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 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".