{"id":"466e6980-3914-55c6-bc7b-42029d762028","stable_key":"availability:deficient-host-viral-variation:1","predicate":"can_favor","statement":"In selenium-deficient mice, experimental passage of Coxsackievirus B3 was associated with reproducible viral genomic changes.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"source_reported: Animal model; the supplied source reports experimental viral sequencing and passage results.","direction":"context_dependent","is_public":true,"mechanism_event_id":"0bb9333e-4494-5f70-b2fc-a3963fb2d32d","mechanism_event_label":"In selenium-deficient mice, experimental passage of Coxsackievirus B3 was associated with reproducible viral genomic changes.","subject":{"id":"dc89d7e2-8f89-577b-838f-42bf5d8ec7c8","slug":"selenium","display_name":"Selenium","entity_type_key":"nutrient_element"},"object":{"id":"214a77a9-0c00-55dd-aa6e-9dfd04e32099","slug":"viral-genomic-variation","display_name":"Viral genomic variation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"0bb9333e-4494-5f70-b2fc-a3963fb2d32d","stable_key":"availability:deficient-host-viral-variation:1","event_type":"availability_dependent_change","label":"In selenium-deficient mice, experimental passage of Coxsackievirus B3 was associated with reproducible viral genomic changes.","description":"Experimental Coxsackievirus passage through selenium-deficient mice. Animal passage experiments; related influenza findings are reported, and vitamin E deficiency produced a similar Coxsackievirus effect.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"dc89d7e2-8f89-577b-838f-42bf5d8ec7c8","slug":"selenium","display_name":"Selenium","entity_type_key":"nutrient_element"},"role":"condition_input","stoichiometry":null,"state_label":"Experimental Coxsackievirus passage through selenium-deficient mice.","sequence_order":0,"notes":""},{"entity":{"id":"214a77a9-0c00-55dd-aa6e-9dfd04e32099","slug":"viral-genomic-variation","display_name":"Viral genomic variation","entity_type_key":"cellular_process"},"role":"affected_component","stoichiometry":null,"state_label":"Experimental Coxsackievirus passage through selenium-deficient mice.","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"Experimental Coxsackievirus passage through selenium-deficient mice.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_scope","value_text":"Animal passage experiments; related influenza findings are reported, and vitamin E deficiency produced a similar Coxsackievirus effect.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The molecular route to individual mutations is unresolved. Selenium is not unique in this respect, and generalization to human infections remains uncertain.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"901b0f41-0a8d-5599-ac1f-9ec4242fd2ba","evidence_kind":"source_passage","locator":"lines 398-412","start_line":398,"end_line":412,"excerpt":"The best-established finding is narrower than the original “selenium uniquely mutates viruses” claim.\n\nselenium deficiency or vitamin E deficiency in experimental mice\n        ↓\nchanged host oxidative / immune environment\n        ↓\nselection or emergence of viral genomic variants\n        ↓\nincreased virulence can persist after transfer to nutritionally adequate mice\n\nDemonstrated in animal models: [10]\n\nCoxsackievirus B3: a normally avirulent strain acquired reproducible genomic changes and increased virulence after passage through selenium-deficient mice.\n\nVitamin E deficiency produced a similar phenomenon in the same Coxsackievirus model. Selenium is therefore not unique among micronutrients in this respect.","model_system":"Supplied reference; verify the primary study and experimental context.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c788c19c-884c-5233-92b1-0bd063d87741","stable_key":"deficiency","title":"Selenium deficiency: a mechanism-first reference","document_type":"user_supplied_reference","citation_label":"Supplied selenium deficiency reference","file_path":"X:\\metabolic-ledger\\source_material\\selenium-deficiency-reference.md","sha256":"a3f14bc3fa24c595dda830664523090a7b5bfa76e9dcf517f42f62212ceb767e","revision_id":"f8f97804-c1fb-56df-9c06-c02e36e2a5b8","review_status":"unverified_draft","notes":"Preserved verbatim. Reported study types are source labels, not independent verification."}}],"relations":[],"conflicts":[],"corrections":[{"id":"a17470e4-bad4-511f-9b29-222d8939ecf5","title":"The viral-passage result does not establish the proposed nucleotide route","kind":"qualification","status":"qualified","why":"The immune draft presents an oxidized nucleotide pool and polymerase-fidelity loss as the route to a permanent virulent strain. The new reference explicitly identifies that detailed chain as a hypothesis unless directly demonstrated.","resolution":"Retain the animal passage and persistence findings, separate them from the unresolved molecular route, and note that vitamin E deficiency produced a similar effect. Do not claim selenium uniqueness or established human generality.","created_at":"2026-09-17 05:59:32","record_type":"qualification","display_label":"Source qualification","record_url":"/corrections/a17470e4-bad4-511f-9b29-222d8939ecf5","literature_review":{"revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1740,"end_line":1745,"papers":[{"paper_key":"beck-1995","title":"Rapid genomic evolution of a non-virulent coxsackievirus B3 in selenium-deficient mice results in selection of identical virulent isolates","url":"https://pubmed.ncbi.nlm.nih.gov/7585090/","doi":"10.1038/nm0595-433","year":1995,"model":"Selenium-deficient mice, viral sequencing and passage","summary":"Stable virulence changes do not establish an oxidized-nucleotide/polymerase-fidelity route."}]},"sides":[{"conflict_id":"a17470e4-bad4-511f-9b29-222d8939ecf5","ordinal":0,"label":"Earlier statement","revision_id":"fbed30e0-1c0d-5b83-8a1f-2867fbe8a5b5","start_line":280,"end_line":286,"quote":"Host Se deficiency\n  → loss of GPX1/GPX4/TrxR buffering\n  → elevated intracellular H₂O₂ and lipid radicals\n  → oxidized nucleotide pool (8-oxo-dGTP) + RdRp fidelity loss\n  → expanded viral quasispecies\n  → selection for virulent variants\n  → new virulent strain, permanent","claim_id":null,"source_key":"immune","source_title":"Selenium in immune cells","claim_ids":[]},{"conflict_id":"a17470e4-bad4-511f-9b29-222d8939ecf5","ordinal":1,"label":"New reference qualification","revision_id":"f8f97804-c1fb-56df-9c06-c02e36e2a5b8","start_line":410,"end_line":418,"quote":"Coxsackievirus B3: a normally avirulent strain acquired reproducible genomic changes and increased virulence after passage through selenium-deficient mice.\n\nVitamin E deficiency produced a similar phenomenon in the same Coxsackievirus model. Selenium is therefore not unique among micronutrients in this respect.\n\nSelenium-deficient mouse models of influenza have also shown increased pathology accompanied by viral genomic changes.\n\nThe exact molecular route from host oxidative stress to each viral mutation is not established. A specific chain such as oxidized nucleotide pool → polymerase fidelity loss → defined virulent strain should be presented as a mechanistic hypothesis unless directly demonstrated.\n\nThe animal work shows that host nutritional state can influence viral evolution. How broadly this applies to human infections remains a separate question.","claim_id":null,"source_key":"deficiency","source_title":"Selenium deficiency: a mechanism-first reference","claim_ids":[]}]}],"research":null}