Seneca Valley virus enters cells through multiple pathways and traffics intracellularly via the endolysosomal pathway
Bibliographic record
Abstract
Seneca Valley virus (SVV, also known as Senecavirus A), an oncolytic virus, is a nonenveloped, positive-strand RNA virus and the sole member of the genus Senecavirus within the family Picornaviridae. The mechanisms of SVV entry into cells are currently almost unknown. In the present study, we found that SVV entry into HEK293T cells is acidic pH-dependent by using ammonium chloride (NH4Cl) and chloroquine, both of which could inhibit SVV infection. We confirmed that dynamin II is required for SVV entry by using dynasore, silencing the dynamin II protein, or expressing the dominant-negative (DN) K44A mutant of dynamin II. Then, we discovered that chlorpromazine (CPZ) treatment or knockdown of the clathrin heavy chain (CLTC) protein significantly inhibited SVV infection. In addition, overexpression of CLTC promoted SVV infection. Caveolin-1 and membrane cholesterol were also required for SVV endocytosis. Notably, utilizing genistein, EIPA or nocodazole, we observed that macropinocytosis and microtubules are not involved in SVV entry. Furthermore, overexpression of the Rab7 and Rab9 proteins but not the Rab5 or Rab11 proteins promoted SVV infection. The findings were further validated by the knockdown of four Rabs and Lamp1 proteins, indicating that after internalization, SVV is transported from late endosomes to the trans-Golgi network (TGN) or lysosomes, respectively, eventually releasing its RNA into the cytosol from the lysosomes. Our findings concretely revealed SVV endocytosis mechanisms in HEK293T cells and provided an insightful theoretical foundation for further research into SVV oncolytic mechanisms.
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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 | 0.001 | 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".