Faculty Opinions recommendation of Evolution of HIV-1 isolates that use a novel Vif-independent mechanism to resist restriction by human APOBEC3G.
Bibliographic record
Abstract
The human APOBEC3G protein restricts the replication of Vif-deficient HIV-1 by deaminating nascent viral cDNA cytosines to uracils, leading to viral genomic strand G-to-A hypermutations [1][2][3][4].However, the HIV-1 Vif protein triggers APOBEC3G degradation, helping explain why this innate defense does not protect patients [5].The APOBEC3G-Vif interaction is a promising therapeutic target, but the benefit of enabling HIV-1 restriction in patients is unlikely to be known until Vif antagonists are developed.As a necessary prelude to such studies, cell-based HIV-1 evolution experiments were done to ask whether APOBEC3G can provide a long-term block to Vifdeficient virus replication and, if so, whether HIV-1 variants would emerge that resist restriction.APOBEC3G-expressing T cells were infected with Vif-deficient HIV-1.Virus infectivity was suppressed in 45/48 cultures for over 5 weeks, but replication was eventually detected in 3 cultures.Virus growth characteristics and sequencing demonstrated that these isolates were still Vif-deficient.Rather, these viruses had acquired a promoter mutation and a Vpr null mutation.Resistance occurred by a novel tolerance mechanism in which the resistant viruses packaged less APOBEC3G and accumulated fewer hypermutations.These data support the development of anti-retrovirals that antagonize Vif and thereby enable endogenous APOBEC3G to suppress HIV-1 replication.
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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 | 0.002 | 0.007 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.004 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.004 | 0.003 |
| Insufficient payload (model declined to judge) | 0.408 | 0.220 |
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".