2023 — HERV-W ENV → linc01930/cGAS axis → neuronal apoptosis
One-paragraph summary
Direct experimental confirmation of the HERV-W ENV ↔ cGAS interaction predicted by the project's HERV-Mitochondrial-Inflammation Loop hypothesis. Demonstrates: (a) cGAS interacts with HERV-W ENV; (b) HERV-W ENV triggers IFN-β expression; (c) HERV-W ENV → cGAS pathway drives neuronal apoptosis in recent-onset schizophrenia patients; (d) the long non-coding RNA linc01930 mediates the HERV-W ENV → cGAS axis. Validates Q40 pipeline mechanism hypothesis at the protein-protein interaction level — provides experimental ground truth for the pipeline's Step 6 docking. Cross-condition support: same HERV-W ENV → cGAS axis operating in schizophrenia subset suggests it's a general post-viral neuroinflammation mechanism rather than disease-specific.
Claims as triples
- HERV_W_ENV — modulates → cGAS_STING_pathway [evidence: protein-protein interaction; confidence: emerging]
- HERV_W_ENV — causes → type_I_IFN [evidence: IFN-β expression; confidence: emerging]
- cGAS_STING_pathway — modulates → neuroinflammation_glial [evidence: schizophrenia subset; confidence: emerging]
Methods note
Cell-line and patient-sample studies. Recent-onset schizophrenia patient PBMCs/serum. Gene-expression analysis identifying linc01930 as mediator. Western blot, IP, functional assays for HERV-W ENV ↔ cGAS interaction.
Limitations
- Schizophrenia, not FM — direct extrapolation requires the same axis to operate in FM.
- Cross-sectional patient samples; doesn't establish temporal direction.
Triangulation notes
- Critical experimental anchor for the HERV-Mitochondrial-Inflammation Loop hypothesis in
synthesis/herv-mitochondrial-inflammation-loop.md. - Mandatory Q40 docking positive control: HERV-W ENV vs cGAS predicted-interaction ipTM should be >0.6; if the pipeline misses this, it has a systematic flaw.
- Cross-condition support: bridge B8 (schizophrenia ↔ FM via shared viral substrate) is now mechanistically anchored at the protein-pathway level.
Bridges
- B8 strengthened — schizophrenia ↔ FM via the HERV-W ENV/cGAS axis.