The highly polymorphic cyclophilin A-binding loop in HIV-1 capsid modulates viral resistance to MxB
Bibliographic record
Abstract
BACKGROUND: The human myxovirus-resistance protein B (MxB, also called Mx2) was recently reported to inhibit HIV-1 infection by impeding the nuclear import and integration of viral DNA. However, it is currently unknown whether there exist MxB-resistant HIV-1 strains in the infected individuals. Answer to this question should address whether MxB exerts an inhibitory pressure on HIV-1 in vivo and whether HIV-1 has evolved to evade MxB inhibition. FINDINGS: We have examined ten transmitted founder (T/F) HIV-1 strains for their sensitivity to MxB inhibition by infecting CD4+ T cell lines SupT1 and PM1 that were stably transduced to express MxB. Two T/F stains, CH040.c and RHPA.c, were found resistant and this resistance phenotype was mapped to the amino acid positions 87 and 208 in viral capsid. The H87Q mutation is located in the cyclophilin A (CypA) binding loop and has a prevalence of 21% in HIV-1 sequences registered in HIV database. This finding prompted us to test other frequent amino acid variants in the CypA-binding region and the results revealed MxB-resistant mutations at amino acid positions 86, 87, 88 and 92 in capsid. All these mutations diminished the interaction of HIV-1 capsid with CypA. CONCLUSIONS: Our results demonstrate the existence of MxB-resistant T/F HIV-1 strains. The high prevalence of MxB-resistant mutations in the CypA-binding loop indicates the significant selective pressure of MxB on HIV-1 replication in vivo especially given that this viral resistance mechanism operates at expense of losing CypA.
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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) | 0.001 | 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 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".