Latent Infection of the Central Nervous System (CNS) and the 'Inside-Out' Model of Multiple Sclerosis (MS) (P1.158)
Bibliographic record
Abstract
OBJECTIVE: To determine if CNS infection with Herpes simplex 1 (HSV-1) results in 'spontaneous molecular reactivation' without the development of recurrent immune mediated CNS demyelination BACKGROUND: The nature of the initial trigger in MS - cytodegenertion (inside-out) or primary autoimmune attack (outside-in) remains controversial. Recently, Stys and colleagues argued in favour of a primary cytodegenerative mechanism as the initiating event with a convolution between progressive cytodegeneration and a variably primed immune system explaining the differences in clinical presentation (Nat Rev Neuro 2012). Previously, we provided evidence that viral infection in the CNS could act as the initiating event with recurrent immune mediated CNS demyelination resulting from acute and spontaneous molecular reactivation of HSV-1 in the CNS combined with an anti-viral T-cell immune response in the periphery of EAE susceptible mouse strains. DESIGN/METHODS: To determine if HSV-1 DNA is present in the brains of BALB/c mice, a strain not developing recurrent demyelination after infection, solution phase PCR was performed during the intermediate (week 10) and late (week 25) stages of infection. Immunohistochemistry studies were performed to identify latently infected CNS cells expressing viral proteins without the development of infectious virus - spontaneous molecular reactivation. RESULTS: Using solution phase PCR, HSV-1 DNA was identified in the brains of BALB/c mice at week 10 and 25 PI. CNS cells, stained with anti-HSV antibody, were identified in BALB/c mice during the intermediate stage of infection and when infectious virus could not be identified - consistent with spontaneous molecular reactivation. CONCLUSIONS: This study provides support for 'spontaneous molecular reactivation' of HSV-1 in BALB/c mice without associated immune mediated CNS demyelination. The results raise the possibility that latent viral infections of the CNS could fulfill the role of a primary cytodegenerative mechanism in an inside-out model of MS. Study Supported by:
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".