HIV‐1 viral protein R causes peripheral nervous system injury associated with <i>in vivo</i> neuropathic pain
Bibliographic record
Abstract
ABSTRACT Painful peripheral neuropathy has become the principal neurological disorder in HIV/AIDS patients. Herein, we investigated the effects of a cytotoxic HIV‐1 accessory protein, viral protein R (Vpr), on the peripheral nervous system (PNS). Host and viral gene expression was investigated in peripheral nerves from HIV‐infected individuals and in HIV‐infected human dorsal root ganglion (DRG) cultures by RT‐PCR and immunocytochemistry. Cytosolic calcium ([Ca 2+ ]) fluxes and neuronal membrane responses were analyzed in cultured DRGs. Neurobehavioral responses and cytokine levels were assessed in a transgenic mouse model in which the vpr transgene was expressed in an immunodeficient background ( vpr/RAG1 −/− ). Vpr transcripts and proteins were detected in peripheral nerves and DRGs from HIV‐infected patients. Exposure of rat or human cultured DRG neurons to Vpr rapidly increased [Ca 2+ ] and action potential frequency while increasing input resistance. HIV infection of human DRG cultures caused neurite retraction ( P <0.05), accompanied by induction of interferon‐α (IFN‐α) transcripts (P<0.05). vpr/RAG1 −/− mice expressed Vpr together with increased IFN‐α ( P <0.05) in the PNS and also exhibited mechanical allodynia, unlike their vpr/RAG1 −/− littermates ( P <0.05). Herein, Vpr caused DRG neuronal damage, likely through cytosolic calcium activation and cytokine perturbation, highlighting Vpr's contribution to HIV‐associated peripheral neuropathy and ensuing neuropathic pain.—Acharjee, S., Noorbakhsh, S., Stemkowski, P. L., Olechowski, C., Cohen, E. A., Ballanyi, K., Kerr, B., Pardo, C., Smith, P. A., Power, C. HIV‐1 viral protein R causes peripheral nervous system injury associated with in vivo neuropathic pain. FASEBJ . 24, 4343–4353 (2010). www.fasebj.org
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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 | 0.002 | 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) | 0.000 | 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".