Herpes Simplex Virus Requires VP11/12 To Activate Src Family Kinase-Phosphoinositide 3-Kinase-Akt Signaling
Bibliographic record
Abstract
We previously showed that the herpes simplex virus 1 (HSV-1) tegument protein VP11/12 activates the lymphocyte-specific Src family kinase (SFK) Lck and is tyrosine phosphorylated in an Lck-dependent manner during T cell infection. We now extend these findings to show that ectopic expression of Lck induces robust tyrosine phosphorylation of VP11/12 in Vero cells, strongly suggesting that VP11/12 participates in an Lck-mediated signaling pathway as a substrate of Lck or a kinase activated by Lck. We sought to elucidate signaling events downstream of VP11/12-SFK interactions. SFKs lie upstream of the canonical phosphoinositide 3-kinase (PI3K)-Akt pathway in signaling emanating from immune receptors, growth factor receptors, and polyomavirus middle T antigen. Here, we show that VP11/12 is required for virus-induced activation of PI3K-Akt signaling in HSV-infected Jurkat T cells and primary fibroblasts. VP11/12 interacts with PI3K or PI3K signaling complexes during infection, suggesting that VP11/12 activates PI3K directly. SFK activity is required for tyrosine phosphorylation of VP11/12, VP11/12-PI3K interactions, and Akt activation in infected fibroblasts, suggesting that SFK-dependent phosphorylation of VP11/12 is required for interactions with downstream signaling effectors. Akt controls many biological functions, including cell survival, cell motility, and translation, but it is currently unclear which Akt targets are modulated by VP11/12 during infection. Although the Akt target mTORC1 is activated during HSV-1 infection, VP11/12 is not required for this effect, implying that one or more additional viral proteins regulate this pathway. Further studies are therefore required to determine which Akt targets and associated biological functions are uniquely modulated by VP11/12.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".