{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T03:39:26Z","timestamp":1784086766989,"version":"3.55.0"},"reference-count":108,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["APMIS"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Since its identification in 1947 and its global emergence in the Americas decades later, the Zika virus (\n                    <jats:styled-content style=\"fixed-case\">ZIKV<\/jats:styled-content>\n                    ) has proven to be a multifaceted challenge to public health. Among the many aspects that remain poorly understood, the complex immunological paradox between Th1 and Th2 responses stands out, playing a central role in the immunopathogenesis of the infection. This narrative review critically explores how scientific literature has addressed this duality, highlighting that an exacerbated Th1 response\u2014although effective in viral containment\u2014is frequently associated with severe outcomes, such as heightened inflammation and autoimmune manifestations, including Guillain\u2010Barr\u00e9 syndrome. Conversely, a predominant Th2 profile, generally linked to milder clinical presentations, may favor viral persistence and, paradoxically, contribute to late\u2010onset neurological complications, such as encephalitis. Additionally, we discuss the central role of interactions between\n                    <jats:styled-content style=\"fixed-case\">CD4<\/jats:styled-content>\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, monocytes,\n                    <jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content>\n                    cells, and B cells, which, although essential for immune control of the infection, may, when dysregulated, exacerbate pathogenesis. By unraveling the mechanisms behind this delicate balance between antiviral defense and immune\u2010mediated damage, we aim to shed light on new therapeutic perspectives. Understanding the nature and consequences of this Th1\/Th2 paradox is crucial for guiding the development of immunomodulatory strategies that foster an effective response against\n                    <jats:styled-content style=\"fixed-case\">ZIKV<\/jats:styled-content>\n                    , while minimizing the risk of neurological injury.\n                  <\/jats:p>","DOI":"10.1111\/apm.70117","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T03:08:38Z","timestamp":1766027318000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The\n                    <scp>TH1<\/scp>\n                    \/\n                    <scp>TH2<\/scp>\n                    Response Imbalance Zika Virus Pathogenesis: An Immunological Paradox"],"prefix":"10.1111","volume":"133","author":[{"given":"Carla","family":"Menezes","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o Em Biologia Parasit\u00e1ria da Amaz\u00f4nia Universidade Do Estado Do Par\u00e1  Bel\u00e9m Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00edvia","family":"Martins","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o Em Biologia Parasit\u00e1ria da Amaz\u00f4nia Universidade Do Estado Do Par\u00e1  Bel\u00e9m Brazil"},{"name":"Se\u00e7\u00e3o de Arbovirologia e Febres Hemorr\u00e1gicas Instituto Evandro Chagas  Ananindeua Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2346-4065","authenticated-orcid":false,"given":"Gustavo","family":"Ferro","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina Universidade Do Estado Do Par\u00e1  Bel\u00e9m Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Arnaud","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina 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