HIV-1 Gp120 clade B/C induces a GRP78 driven cytoprotective mechanism in astrocytoma
Bibliographic record
Abstract
// Sheila N. López 1 , Madeline Rodríguez-Valentín 1 , Mariela Rivera 1 , Maridaliz Rodríguez 1 , Mohan Babu 2 , Luis A. Cubano 1 , Huangui Xiong 3 , Guangdi Wang 4 , Lilia Kucheryavykh 5 and Nawal M. Boukli 1 1 Biomedical Proteomics Facility, Department of Microbiology and Immunology, Universidad Central del Caribe, School of Medicine, Bayamón, PR, USA 2 Department of Biochemistry, Research and Innovation Center, University of Regina, Saskatchewan, Canada 3 Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA 4 RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA, USA 5 Department of Biochemistry, Universidad Central del Caribe, School of Medicine, Bayamón, PR, USA Correspondence to: Nawal M. Boukli, email: nawal.boukli@uccaribe.edu Keywords: HIV-1 clades B and C, Gp120, GRP78, quantitative proteomics (tandem mass tag), unfolded protein response (UPR) Received: March 24, 2017     Accepted: June 28, 2017     Published: July 22, 2017 ABSTRACT HIV-1 clades are known to be one of the key factors implicated in modulating HIV-associated neurocognitive disorders. HIV-1 B and C clades account for the majority of HIV-1 infections, clade B being the most neuropathogenic. The mechanisms behind HIV-mediated neuropathogenesis remain the subject of active research. We hypothesized that HIV-1 gp120 clade B and C proteins may exert differential proliferation, cell survival and NeuroAIDS effects in human astrocytoma cells via the Unfolded Protein Response, an endoplasmic reticulum- based cytoprotective mechanism. The differential effect of gp120 clade B and C was evaluated using for the first time a Tandem Mass Tag isobaric labeling quantitative proteomic approach. Flow cytometry analyses were performed for cell cycle and cell death identification. Among the proteins differentiated by HIV-1 gp120 proteins figure cytoskeleton, oxidative stress, UPR markers and numerous glycolytic metabolism enzymes. Our results demonstrate that HIV-1 gp120 B induced migration, proliferative and protective responses granted by the expression of GRP78, while HIV-1 gp120 C induced the expression of key inflammatory and pro-apoptotic markers. These novel findings put forward the first evidence that GRP78 is a key player in HIV-1 clade B and C neuropathogenic discrepancies and can be used as a novel target for immunotherapies.
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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 | 0.000 | 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 | 0.005 |
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".