{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T12:24:08Z","timestamp":1793276648280,"version":"4.5.0"},"reference-count":84,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005297","name":"Medical University of Bialystok","doi-asserted-by":"publisher","award":["B.SUB.25.106"],"award-info":[{"award-number":["B.SUB.25.106"]}],"id":[{"id":"10.13039\/501100005297","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Enterovirus A71 (EV-A71) is a critical global pathogen, primarily causing Hand-Foot-and-Mouth Disease (HFMD) but frequently leading to severe neurological complications, including fatal neurogenic pulmonary edema (PE). This review elucidates the complex interplay between viral pathogenesis and the host immune response. EV-A71 utilizes receptors like SCARB2 and PSGL-1 for entry, while its proteases (2Apro, 3Cpro) efficiently evade innate immunity by cleaving key signaling adaptors (MAVS, TRIF), suppressing Type I IFN response. Critical to disease progression is the age-dependent vulnerability in infants and the subsequent shift toward immunopathology. Severe disease is driven by a systemic cytokine storm and T cell dysregulation, characterized by a loss of control from Treg cells and a profound Th17\/Treg imbalance, resulting in high levels of pathogenic cytokines (e.g., IL-17A, IFN-\u03b3). Clinical progression is predicted by specific biomarkers, including Treg depletion, monocyte exhaustion (PD-1\/PD-L1), and suppressed regulatory signaling (low cAMP). These findings highlight that effective therapeutic strategies must target host-mediated damage through immunomodulation (e.g., by exploring interventions against key pathogenic axes like IL-6 and IL-1\u03b2) and call for the development of next-generation vaccines capable of eliciting balanced cellular immunity to prevent immunopathology.<\/jats:p>","DOI":"10.3390\/v17121540","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T08:50:20Z","timestamp":1764060620000},"page":"1540","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Host Immune Response to Enterovirus A71 (EV-A71): From Viral Immune Evasion to Immunopathology and Prognostic Biomarkers of Severe Disease\u2014A Narrative Review"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9655-3595","authenticated-orcid":false,"given":"Anna","family":"Andronik","sequence":"first","affiliation":[{"name":"Department of Pediatric Infectious Diseases, Medical University of Bialystok, Waszyngtona 17, 15-274 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9004-8623","authenticated-orcid":false,"given":"Dawid","family":"Lewandowski","sequence":"additional","affiliation":[{"name":"Department of Pediatric Infectious Diseases, Medical University of Bialystok, Waszyngtona 17, 15-274 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8391-4793","authenticated-orcid":false,"given":"Artur","family":"Sulik","sequence":"additional","affiliation":[{"name":"Department of Pediatric Infectious Diseases, Medical University of Bialystok, Waszyngtona 17, 15-274 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0309-6987","authenticated-orcid":false,"given":"Kacper","family":"Toczylowski","sequence":"additional","affiliation":[{"name":"Department of Pediatric Infectious Diseases, Medical University of Bialystok, Waszyngtona 17, 15-274 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e42183","DOI":"10.1097\/MD.0000000000042183","article-title":"Insights into the mechanisms of apoptosis and pathogenesis in enterovirus 71 infections A review","volume":"104","author":"Wu","year":"2025","journal-title":"Medicine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1080\/22221751.2019.1644142","article-title":"Intra-host emergence of an enterovirus A71 variant with enhanced PSGL1 usage and neurovirulence","volume":"8","author":"Sun","year":"2019","journal-title":"Emerg. 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