Nef-mediated ARP2/3 inhibition drives CD4+ T cell dysfunction and dysregulated immunity in HIV progressors 2658
Bibliographic record
Abstract
Abstract Description The life cycle of HIV is heavily influenced by actin cytoskeleton dynamics. We hypothesize that HIV Nef inhibits ARP2/3-mediated actin branching, leading to defects in CD4+ T cell function and immune dysregulation in HIV progressors. We used spatial transcriptomics to assess gene expression changes in lymph nodes at different stages of HIV disease. CD4+ T cells within viremic tissues showed significantly altered proinflammatory signatures and reduced ARP2/3 gene expression. Further analysis of HIV-infected primary human CD4+ T cells was performed using ultrastructural and time-lapse microscopy. HIV infection induced five distinct abnormal phenotypes, including a pointed needle-like structure and polarized blebbing at the lamellipodium. These pathological morphologies are identical to those seen in leukocytes from patients with ARP2/3-deficient primary immunodeficiencies. Reporter viruses were used to show that HIV Nef significantly contributed to the phenotypes. Our findings suggest that HIV Nef contributes to ARP2/3 inhibition, disrupting CD4+ T cell function and immunity in normal HIV progressors. Although every normal progressor or uninfected control exhibited these cytopathologies, two-thirds of HIV controllers we tested maintained cortical actin stability despite productive HIV infection, suggesting inherent resistance to Nef-mediated ARP2/3 inhibition. Restoring ARP2/3 functionality may improve therapeutic strategies that target the reservoir in HIV progressors. Funding Sources Funded in part by NIH grants UM1AI126617, UM1AI164559, U01DA058527, R01CA260691, and R01DA052027. Topic Categories Viral Immunology (VIR)
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".