Virus specific CD8+ T cells protect against mouse hepatitis virus central nervous system disease
Bibliographic record
Abstract
This thesis aimed at more clearly defining the role of virus-specific CD8+ T cells in protection from both acute encephalitis and chronic demyelination induced by mouse hepatits virus (MHV). MHV pathogenesis in the mouse largely depends on the strain used. The ability of CD8+ T cell epitope escape to contribute to virus persistence and demyelination was investigated by selecting recombinant strains of MHV that contained a single amino acid substitution within the immunodominant epitope of the spike protein that abrogated its recognition. This mutation resulted in attenuation, demonstrating that epitope escape alone is not sufficient to establish persistence and highlights the important trade-off between evading the immune response and maintaining structural and functional integrity of the spike. The role of CD8+ T cells in protecting MHV-infected mice from acute encephalitis was assessed using an adoptive transfer system in which epitope-specific CD8+ T cells were transferred at different times during the course of acute infection with the MHV-RA59 strain. These studies revealed that an early robust epitope-specific CD8+ T cell response protects against acute encephalitis and was essential for protection from virus spread to the spinal cord and demyelination. Further analysis using the adoptive transfer system showed that virus-specific CD8+ T cells are primed during the first two days following infection with the mildly neurovirulent MHV-RA59 strain. However, infection with the highly neurovirulent strain, MHV-RJHM, does not prime epitope-specific CD8+ T cells. We also observed that both strains of MHV infected bone marrow derived dendritic cells (BMDCs), professional antigen presenting cells. Interestingly, MHV-RJHM infection induced the formation of very large syncytia, possibly limiting the capacity of these cells to present antigen for T cell priming. Thus, in order to limit MHV pathogenesis a strong CD8+ T cell response is required and the ability of MHV-RJHM to evade the priming of a virus-specific CD8+ T cell response contributes to its highly neurovirulent phenotype.
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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 | 0.001 |
| 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".