Hepatitis C Virus–Infected Cells Downregulate NKp30 and Inhibit Ex Vivo NK Cell Functions
Bibliographic record
Abstract
Hepatitis C virus (HCV) successfully evades the immune system and establishes chronic infection in ∼80% of cases. Immune evasion may involve modulating NK cell functions. Therefore, we developed a short-term assay to assess immediate effects of HCV-infected cells on ex vivo NK cytotoxicity and cytokine production. Natural cytotoxicity, Ab-dependent cell-mediated cytotoxicity, IFN-γ production, and TNF-α production were all significantly inhibited by short-term direct exposure to HCV-infected hepatoma-derived Huh-7.5 cells. Inhibition required cell-to-cell contact and increased together with multiplicity of infection and HCV protein levels. Blocking potential interaction between HCV E2 and NK CD81 did not abrogate NK cell inhibition mediated by HCV-infected cells. We observed no change in expression levels of NKG2D, NKG2A, NKp46, or CD16 on NK cells exposed to HCV-infected Huh-7.5 cells for 5 h or of human histocompatibility-linked leukocyte Ag E on HCV-infected compared with uninfected Huh-7.5 cells. Inhibition of ex vivo NK functions did correspond with reduced surface expression of the natural cytotoxicity receptor NKp30, and downregulation of NKp30 was functionally reflected in reduced anti-NKp30 redirected lysis of P815 cells. Infection of Huh-7.5 cells with HCV JFH1(T) increased surface binding of an NKp30-IgG1 Fcγ fusion protein, suggesting upregulation of an antagonistic NKp30 ligand on HCV-infected cells. Our assay demonstrates rapid inhibition of critical NK cell functions by HCV-infected cells. Similar localized effects in vivo may contribute to establishment of chronic HCV infection and associated phenotypic and functional changes in the NK population.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".