STAT1-dependent tolerance of intestinal viral infection
Bibliographic record
Abstract
Abstract The diverse commensal ecosystem present in the mammalian intestine requires the host immune system to maintain a tolerogenic environment. The virome is an understudied component of the microbiota which promotes intestinal homeostasis and protection from injury, but the host mechanisms that regulate tolerance to viral commensals are poorly described. The antiviral signal transducer STAT1 has previously been shown to mediate tolerance to systemic viral pathogens by suppressing adaptive immune responses and protecting the host from immunopathology, but we sought to characterize its role in the context of a commensal intestinal viral infection. We used a persistent strain of murine norovirus (MNV CR6) to interrogate host mechanisms of viral tolerance and commensalism, as CR6 has previously been shown to promote intestinal homeostasis. While CR6 infections of wildtype mice were asymptomatic and limited to the colon, STAT1-deficient mice exhibited virus-induced weight loss and mortality accompanied by systemic viral spread, colonic bacterial dysbiosis, CD4+ T cell dysfunction and hyperaccumulation of CD8+ T cells. However, clinical manifestation of virus-induced disease in STAT1-deficient mice was independent of T cells and the bacterial microbiota. Instead, therapeutic control of viral replication was sufficient to prevent virus-induced disease despite ongoing T cell dysregulation. Collectively, our data indicate that STAT1 maintains tolerance to a viral component of the intestinal microbiota by control of viral replication rather than immunopathology, suggesting that STAT1 uses distinct strategies to tolerate pathogenic and commensal viruses.
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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) | 0.002 | 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 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".