High dimensional analysis of the GI tract as a long-term reservoir for chronic viral infection
Bibliographic record
Abstract
Abstract Chronic viruses such as HIV and hepatitis are a major health concern worldwide. As an organ constantly exposed to the external environment, the gastrointestinal tract (GIT) must constantly balance suppressive and inflammatory immunity, making it an ideal organ for virus persistence. Yet despite its importance, chronic virus infection of the GIT and its ramifications towards host immunity remains poorly understood. We recently discovered that the GIT is a long-term reservoir for chronic lymphocytic choriomeningitis virus (LCMV); persisting well after virus is cleared from the blood and other peripheral tissues. To identify host and microbial alterations that facilitate chronic GIT infection we performed high dimensional CyTOF analysis, 16s rRNA-seq and next generation sequencing. Primary infection induced acute CD4 T cell ablation and chronic infection promoted Treg outgrowth, which was associated with viral persistence. Interestingly, chronic infection led to acute GI pathology and dysbiosis, with long-term infection enhancing susceptibility to IBD. Transcriptional signatures indicated enhanced type I interferon induced inflammation and metabolic changes associated with immune exhaustion. Interestingly, upstream regulators of GIT immunity were shared in chronic LCMV, HIV and SIV, indicating the induction of conserved pathways across multiple viral infections. Finally, we demonstrate the efficacy of immunotherapeutic targets and cell depletions to control the long-lived chronic GIT reservoir. Ultimately our studies define molecular, cellular and microbial impacts of chronic virus infection to alter GI function and identify potential immunotherapeutic strategies to control virus in this long-lived reservoir.
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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 | 0.001 | 0.001 |
| 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".