APOBEC3 Host Restriction Factors of HIV-1 Can Change the Template Switching Frequency of Reverse Transcriptase
Bibliographic record
Abstract
The APOBEC3 family of deoxycytidine deaminases has the ability to restrict HIV-1 through deamination-dependent and deamination-independent mechanisms. Although the generation of mutations through deamination of cytosine to uracil in single-stranded HIV-1 (-) DNA is the dominant mechanism of restriction, the deaminase-independent mechanism additionally contributes. Previous observations indicate that APOBEC3 enzymes competitively bind the RNA template or reverse transcriptase (RT) and act as a roadblock to DNA polymerization. Here we studied how the deamination-independent inhibition of HIV-1 RT by APOBEC3C S188I, APOBEC3F, APOBEC3G, and APOBEC3H affected RT template switching. We found that APOBEC3F could promote template switching of RT, and this was dependent on the high affinity with which it bound nucleic acids, suggesting than an APOBEC3 "road-block" can force template switching. Our data demonstrate that the deamination-independent functions of APOBEC3 enzymes extend beyond only disrupting RT DNA polymerization. Since alterations to the RT template switching frequency can result in insertions or deletions, our data support a model in which APOBEC3 enzymes use multiple mechanisms to increase the probability of generating a mutated and nonfunctional virus in addition to cytosine deamination.
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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 | 0.000 | 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) | 0.002 | 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".