{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T10:13:47Z","timestamp":1788344027196,"version":"build-2803163510"},"reference-count":98,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006407","name":"Natural Science Foundation of Henan Province","doi-asserted-by":"publisher","award":["262300421517"],"award-info":[{"award-number":["262300421517"]}],"id":[{"id":"10.13039\/501100006407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019331","name":"Henan Medical Science and Technique Foundation","doi-asserted-by":"publisher","award":["252103810370"],"award-info":[{"award-number":["252103810370"]}],"id":[{"id":"10.13039\/501100019331","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    N6-methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A), the most abundant internal RNA modification in eukaryotic cells, has emerged as a critical regulator of antiviral host defense. Increasing evidence indicates that m\n                    <jats:sup>6<\/jats:sup>\n                    A functions beyond conventional post-transcriptional regulation by dynamically coordinating the magnitude, timing, and duration of immune responses during viral infection. In SARS-CoV-2 infection, dysregulated antiviral immunity is characterized by delayed interferon activation together with sustained inflammatory responses, suggesting the existence of regulatory mechanisms that continuously calibrate immune signaling rather than simply switching it on or off. In this review, we propose the concept of m6A as a potential \u201cepitranscriptomic immune rheostat,\u201d representing a conceptual framework in which m6A may fine-tune antiviral immunity through coordinated regulation of RNA stability, translational efficiency, and transcript turnover. We summarize how m\n                    <jats:sup>6<\/jats:sup>\n                    A shapes multiple layers of innate immune responses, including pattern recognition receptor sensing, type I interferon signaling, inflammatory buffering, and immune resolution. We further discuss emerging evidence suggesting that SARS-CoV-2 infection is associated with dynamic modulation of the m\n                    <jats:sup>6<\/jats:sup>\n                    A regulatory machinery and viral RNA methylation landscapes, while emphasizing that many mechanistic insights remain to be experimentally validated in SARS-CoV-2 models. In addition, we highlight the interplay between m\n                    <jats:sup>6<\/jats:sup>\n                    A regulation and immunometabolic remodeling, while distinguishing direct SARS-CoV-2 evidence from findings derived from other viral systems or broader m\n                    <jats:sup>6<\/jats:sup>\n                    A biology. Selected comparisons with Influenza A virus are discussed as complementary evidence to explore potentially conserved principles of m\n                    <jats:sup>6<\/jats:sup>\n                    A-mediated immune regulation among RNA viruses rather than as direct evidence for SARS-CoV-2 infection. Finally, we discuss the therapeutic implications of targeting the m\n                    <jats:sup>6<\/jats:sup>\n                    A regulatory network to recalibrate immune responses with temporal and cellular precision, while noting that current m\n                    <jats:sup>6<\/jats:sup>\n                    A-targeting strategies remain at the preclinical proof-of-concept stage and require further evaluation regarding specificity, safety, and translational feasibility. Collectively, this review provides a hypothesis-driven conceptual framework for understanding how m\n                    <jats:sup>6<\/jats:sup>\n                    A integrates RNA fate control with antiviral immunity and immunopathology during SARS-CoV-2 infection.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1878455","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T09:19:40Z","timestamp":1788340780000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["N6-methyladenosine as a potential epitranscriptomic immune rheostat during SARS-CoV-2 infection"],"prefix":"10.3389","volume":"17","author":[{"given":"Xianfeng","family":"Hui","sequence":"first","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Henan Medical University","place":["Xinxiang, 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