{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:47:07Z","timestamp":1790282827184,"version":"4.1.0"},"reference-count":55,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2026,2,17]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      N6-methyladenosine (m\n                      <jats:sup>6<\/jats:sup>\n                      A) is the most abundant internal modification in eukaryotic RNA and plays diverse roles in RNA metabolism. Increasing evidence indicates that m\n                      <jats:sup>6<\/jats:sup>\n                      A is also present in viral RNAs, where it exerts virus-specific effects. While several studies have shown that m\n                      <jats:sup>6<\/jats:sup>\n                      A can facilitate viral replication, its antiviral mechanisms remain less understood. In this study, we used transmissible gastroenteritis virus (TGEV) as a model to investigate the inhibitory role of m\n                      <jats:sup>6<\/jats:sup>\n                      A in viral infection. We demonstrated that m\n                      <jats:sup>6<\/jats:sup>\n                      A modification is present in the TGEV genome and suppresses viral replication. The m\n                      <jats:sup>6<\/jats:sup>\n                      A reader proteins bind to viral RNA and reduce the stability of m\n                      <jats:sup>6<\/jats:sup>\n                      A-modified transcripts. Notably, TGEV infection increased global m\n                      <jats:sup>6<\/jats:sup>\n                      A levels in host RNA, particularly in interferon (IFN)-associated genes. Inhibition of m\n                      <jats:sup>6<\/jats:sup>\n                      A methylation significantly diminished IFN gene expression. Furthermore, compared to other viruses, TGEV genomic RNA displayed an abnormally higher m\n                      <jats:sup>6<\/jats:sup>\n                      A ratio, which can be distinguished by RIG-I to promote an immune response. Collectively, our findings reveal that high m\n                      <jats:sup>6<\/jats:sup>\n                      A modification enhances RIG-I-mediated sensing of TGEV RNA, leading to the activation of IFN responses and inhibition of viral replication. This study provides new insights into the complex regulatory functions of m\n                      <jats:sup>6<\/jats:sup>\n                      A during viral infection and host antiviral defense.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        N6-methyladenosine (m\n                        <jats:sup>6<\/jats:sup>\n                        A) is one of the most prevalent RNA modifications in viral genomes, but its functional impact varies widely across viruses. While m\n                        <jats:sup>6<\/jats:sup>\n                        A often promotes viral replication, it can exert inhibitory effects in certain viruses, particularly within the\n                        <jats:italic toggle=\"yes\">Flaviviridae<\/jats:italic>\n                        and\n                        <jats:italic toggle=\"yes\">Coronaviridae<\/jats:italic>\n                        families. Despite growing evidence of this antiviral role, the underlying mechanisms remain largely unclear. Here, we used transmissible gastroenteritis virus (TGEV), a swine coronavirus, as a model to explore the inhibitory function of m\n                        <jats:sup>6<\/jats:sup>\n                        A. We show that the TGEV genome harbors a relatively high density of m\n                        <jats:sup>6<\/jats:sup>\n                        A modification compared to other viruses and host mRNA, which are efficiently detected by the host pattern recognition receptor RIG-I. This interaction enhances innate immune activation and restricts viral replication. Our findings uncover the mechanism by which abnormal m\n                        <jats:sup>6<\/jats:sup>\n                        A modification can be sensed to activate antiviral immunity and provide deeper insight into the multifaceted role of m\n                        <jats:sup>6<\/jats:sup>\n                        A in host\u2013virus interactions.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.01373-25","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T18:54:27Z","timestamp":1767207267000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["N6-methyladenosine within transmissible gastroenteritis virus genomic RNA inhibits its replication via efficient recognition by RNA sensor 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