Vpu Exerts a Positive Effect on HIV-1 Infectivity by Down-modulating CD4 Receptor Molecules at the Surface of HIV-1-producing Cells
Bibliographic record
Abstract
Human immunodeficiencey virus, type 1 (HIV-1) encodes three proteins, Nef, Vpu, and gp160, that down-modulate surface expression of the CD4 receptor during viral infection. In the present study, we have investigated the role of CD4 down-modulation in the HIV-1 infection cycle, primarily from the perspective of Vpu function. We report here that, like Nef, Vpu-mediated CD4 degradation modulates positively HIV-1 infectivity. Our data reveal that accumulation of CD4 at the cell surface of Vpu-deficient HIV-1-producing cells leads to an efficient recruitment of CD4 into virions and to an impairment of viral infectivity. This CD4-mediated inhibition of viral infectivity was not observed when a CD4 mutant unable to bind Env gp120 was used or when VSV-G glycoprotein was utilized to pseudotype viruses, suggesting that an interaction between CD4 and gp120 is required for interference. Indeed, protein analysis of Vpu-defective viral particles reveals that CD4 recruitment is associated with an increased formation of gp120-CD4 complexes at the virion surface. Interestingly, we did not detect any difference at the level of total virion-associated Env glycoproteins between wild-type and Vpu-defective virus, indicating that accumulation of CD4 at the cell surface and recruitment of CD4 into Vpu-defective HIV-1 particles exert a negative effect on viral infectivity, most likely by promoting the formation of nonfunctional gp120-CD4 complexes at the virion surface. Finally, we show that both Vpu- and Nef-induced CD4 down-modulation activities are required for production of fully infectious particles in CD4+ T cell lines and primary cells, an observation that has clear implications for viral spread in vivo.
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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 | 0.001 | 0.001 |
| 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) | 0.001 | 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 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".