Mutation of UL24 impedes the dissemination of acute herpes simplex virus 1 infection from the cornea to neurons of trigeminal ganglia
Bibliographic record
Abstract
Herpes simplex virus 1 (human herpesvirus 1) initially infects epithelial cells of the mucosa and then goes on to infect sensory neurons leading ultimately to a latent infection in trigeminal ganglia (TG). UL24 is a core herpesvirus gene that has been identified as a determinant of pathogenesis in several Alphaherpesvirinae, although the underlying mechanisms are unknown. In a mouse model of ocular infection, a UL24-deficient virus exhibited a reduction in viral titres in tear films of 1 log10, whilst titres in TG are often below the level of detection. Moreover, the efficiency of reactivation from latency was also severely reduced. Herein, we investigated how UL24 contributed to acute infection of TG. Our results comparing the impact of UL24 on viral titres in eye tissue versus in tear films did not reveal a general defect in virus release from the cornea. We also found that the impairment of replication seen in mouse primary embryonic neurons with a UL24-deficient virus was not more severe than that observed in an epithelial cell line. Rather, in situ histological analyses revealed that infection with a UL24-deficient virus led to a significant reduction in the number of acutely infected neurons at 3 days post-infection (p.i.). Moreover, there was a significant reduction in the number of neurons positive for viral DNA at 2 days p.i. for the UL24-deficient virus as compared with that observed for WT or a rescue virus. Our results supported a model whereby UL24 functions in the dissemination of acute infection from the cornea to neurons in TG.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".